WO2014165727A1 - Antimicrobial treatment of medical device surfaces - Google Patents

Antimicrobial treatment of medical device surfaces Download PDF

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Publication number
WO2014165727A1
WO2014165727A1 PCT/US2014/032919 US2014032919W WO2014165727A1 WO 2014165727 A1 WO2014165727 A1 WO 2014165727A1 US 2014032919 W US2014032919 W US 2014032919W WO 2014165727 A1 WO2014165727 A1 WO 2014165727A1
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WO
WIPO (PCT)
Prior art keywords
coating
vessel
contact surface
catheter
plasma
Prior art date
Application number
PCT/US2014/032919
Other languages
French (fr)
Inventor
Robert S. Abrams
Original Assignee
Sio2 Medical Products, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sio2 Medical Products, Inc. filed Critical Sio2 Medical Products, Inc.
Publication of WO2014165727A1 publication Critical patent/WO2014165727A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L9/00—Disinfection, sterilisation or deodorisation of air
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00889—Material properties antimicrobial, disinfectant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/10—Materials for lubricating medical devices

Definitions

  • the invention concerns an improved medical device comprising: a surface which is configured to contact a human or animal fluid or tissue or a pharmaceutical preparation; and silver ions or other antimicrobial material coated in or incorporated on the surface in an amount effective to inhibit microbial growth on or adjacent to the surface.
  • Nosocomial, or hospital-related bacterial infections are estimated to be the fifth- leading cause of death in the United States, after heart disease, cancer, stroke, and pneumonia or flu.
  • the Centers for Disease Control estimate that nosocomial infections cost hospitals more than $2300 per patient for diagnosis and treatment. Many instances, such as vascular catheter infection, can cost $25,000 per episode. Overall, the infections cost hospitals $4.8 billion annually in extended care and treatment.
  • Silver is effective across a broad range of bacteria and against mutating pathogens. It is also effective in blocking fungi and yeasts known to cause disease.
  • silver 70-88 ⁇ g of silver each day.
  • Other heavy metals such as mercury and lead, can bond chemically and accumulate in the body, which can inhibit metabolism.
  • silver is, for the most part, nontoxic. Cases of extreme exposure have caused upper respiratory or mild eye irritation, and prolonged exposure can cause argyria.
  • silver oxide is an effective antimicrobial at levels as little as 1 ppm, so toxicity concerns are mostly irrelevant.
  • U.S. Published Patent Application 2006-0198903 Al states that it relates to "efficient methods for depositing highly adherent anti-microbial materials onto a wide range of surfaces. A controlled cathodic arc process is described, which results in enhanced adhesion of silver oxide to polymers and other surfaces, such as surfaces of medical devices. Deposition of anti-microbial materials directly onto the contact surfaces is possible in a cost- effective manner that maintains high anti-microbial activity over several weeks when the coated devices are employed in vivo.” This application is hereby incorporated by reference in its entirety here. See also PCT Published Application WO03044240A1.
  • Storey et al. also identifies several alternative metals for antimicrobial use: gold, platinum, copper, tantalum, titanium, zirconium, hafnium, and zinc.
  • Storey et al. identifies a metal or polymeric surface as potential contact surfaces for antimicrobial treatment, and states that "the Ag/AgO impregnates the metal contact surface up to a depth of about 10 nanometers," and a polymeric contact surface "up to a depth of about 100 nanometers.”
  • Exemplary polymeric contact surfaces identified are: "polypropylene, polyurethane, EPTFE, PTFE, polyimide, polyester, PEEK, UHMWPE, and nylon.”
  • Biofilm formation is extremely difficult to eliminate once it has begun. Preventing biofilms on medical devices and implants is key to controlling their contribution to establishing infection. Because biofilm formation is dependent upon a surface, one strategy is to modify the surface to make it hostile to microorganisms. Ionic silver is becoming a favored substance for surface modification for a number of reasons, including the following: [0014] "It has broad-spectrum antimicrobial action.
  • IPD Ionic Plasma Deposition
  • An aspect of the present invention is a method of making an antimicrobial medical device.
  • a medical device or material or portion thereof comprising a contact surface.
  • a first treatment of SiOx, SiOxCy, or SiNxCy is applied to the contact surface.
  • a second antimicrobially effective treatment is applied to the contact surface.
  • the second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
  • FIG. 1 is a schematic diagram showing a vessel processing system according to an embodiment of the disclosure.
  • FIG. 2 is a schematic sectional view of a vessel holder in a coating station according to an embodiment of the disclosure.
  • FIG. 3 is a view similar to FIG. 2 of an alternative embodiment of the disclosure.
  • FIG. 4 is a diagrammatic plan view of an alternative embodiment of the vessel holder.
  • FIG. 5 is a diagrammatic plan view of another alternative embodiment of the vessel holder.
  • FIG. 6 is a view similar to FIG. 2 of vessel inspection apparatus.
  • FIG. 7 is a view similar to FIG. 2 of alternative vessel inspection apparatus.
  • FIG. 8 is a section taken along section lines A— A of FIG. 2.
  • FIG. 9 is an alternative embodiment of the structure shown in FIG. 8.
  • FIG. 10 is a view similar to FIG. 2 of a vessel holder in a coating station according to another embodiment of the disclosure, employing a CCD detector.
  • FIG. 11 is a detail view similar to FIG. 10 of a light source and detector that are reversed compared to the corresponding parts of FIG. 6.
  • FIG. 12 is a view similar to FIG. 2 of a vessel holder in a coating station according to still another embodiment of the disclosure, employing microwave energy to generate the plasma.
  • FIG. 13 is a view similar to FIG. 2 of a vessel holder in a coating station according to yet another embodiment of the disclosure, in which the vessel can be seated on the vessel holder at the process station.
  • FIG. 14 is a view similar to FIG. 2 of a vessel holder in a coating station according to even another embodiment of the disclosure, in which the electrode can be configured as a coil.
  • FIG. 15 is a view similar to FIG. 2 of a vessel holder in a coating station according to another embodiment of the disclosure, employing a tube transport to move a vessel to and from the coating station.
  • FIG. 16 is a diagrammatic view of the operation of a vessel transport system, such as the one shown in FIG. 15, to place and hold a vessel in a process station.
  • FIG. 17 is a diagrammatic view of a mold and mold cavity for forming a vessel according to an aspect of the present disclosure.
  • FIG. 18 is a diagrammatic view of the mold cavity of FIG. 17 provided with a vessel coating device according to an aspect of the present disclosure.
  • FIG. 19 is a view similar to FIG. 17 provided with an alternative vessel coating device according to an aspect of the present disclosure.
  • FIG. 20 is an exploded longitudinal sectional view of a syringe and cap adapted for use as a prefilled syringe.
  • FIG. 21 is a view generally similar to FIG. 2 showing a capped syringe barrel and vessel holder in a coating station according to an embodiment of the disclosure.
  • FIG. 22 is a view generally similar to FIG. 21 showing an uncapped syringe barrel and vessel holder in a coating station according to yet another embodiment of the invention.
  • FIG. 23 is a perspective view of a blood collection tube assembly having a closure according to still another embodiment of the invention.
  • FIG. 24 is a fragmentary section of the blood collection tube and closure assembly of FIG. 23.
  • FIG. 25 is an isolated section of an elastomeric insert of the closure of FIGS. 23 and 24.
  • FIG. 26 is a view similar to FIG. 22 of another embodiment of the invention for processing syringe barrels and other vessels.
  • FIG. 27 is an enlarged detail view of the processing vessel of FIG. 26.
  • FIG. 28 is a schematic view of an alternative processing vessel.
  • FIG. 29 is a schematic view showing outgassing of a material through a coating.
  • FIG. 30 is a schematic sectional view of a test set-up for causing outgassing of the wall of a vessel to the interior of the vessel and measurement of the outgassing using a measurement cell interposed between the vessel and a source of vacuum.
  • FIG. 31 is a plot of outgassing mass flow rate measured on the test-set-up of FIG. 30 for multiple vessels.
  • FIG. 32 is a bar graph showing a statistical analysis of the endpoint data shown in FIG. 31.
  • FIG. 33 is a longitudinal section of a combined syringe barrel and gas receiving volume according to another embodiment of the invention.
  • FIG. 34 is a view similar to FIG 34 of another embodiment of the invention including an electrode extension.
  • FIG. 35 is a view taken from section lines 35 - 35 of FIG. 34, showing the distal gas supply openings and extension electrode of FIG. 34.
  • FIG. 36 is a perspective view of a double-walled blood collection tube assembly according to still another embodiment of the invention.
  • FIG. 37 is a view similar to FIG. 22 showing another embodiment.
  • FIG. 38 is a view similar to FIG. 22 showing still another embodiment.
  • FIG. 39 is a view similar to FIG. 22 showing yet another embodiment.
  • FIG. 40 is a view similar to FIG. 22 showing even another embodiment.
  • FIG. 41 is a plan view of the embodiment of FIG. 40.
  • FIG. 42 is a fragmentary detail longitudinal section of an alternative sealing arrangement, usable for example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12- 16, 18, 19, 33, and 37-41 for seating a vessel on a vessel holder.
  • FIG. 42 also shows an alternative syringe barrel construction usable, for example, with the embodiments of FIGS. 2, 3, 6-10, 12-22, 26-28, 33- 34, and 37-41.
  • FIG. 43 is a further enlarged detail view of the sealing arrangement shown in FIG. 42.
  • FIG. 44 is a view similar to FIG. 2 of an alternative gas delivery tube/inner electrode usable, for example with the embodiments of FIGS. 1, 2, 3, 8, 9, 12-16, 18-19, 21-22, 33, 37-43, 46-49, and 52-54.
  • FIG. 45 is an alternative construction for a vessel holder usable, for example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12-16, 18, 19, 21, 22, 26, 28, 33-35, and 37-44.
  • FIG. 46 is a schematic sectional view of an array of gas delivery tubes and a mechanism for inserting and removing the gas delivery tubes from a vessel holder, showing a gas delivery tube in its fully advanced position.
  • FIG. 47 is a view similar to FIG. 46, showing a gas delivery tube in an intermediate position.
  • FIG. 48 is a view similar to FIG. 46, showing a gas delivery tube in a retracted position.
  • the array of gas delivery tubes of FIGS. 46-48 are usable, for example, with the embodiments of FIGS. 1, 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-45, 49, and 52-54.
  • the mechanism of FIGS. 46-48 is usable, for example, with the gas delivery tube embodiments of FIGS. 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-45, 49, and 52-54, as well as with the probes of the vessel inspection apparatus of FIGS. 6 and 7.
  • FIG. 49 is a view similar to FIG. 16 showing a mechanism for delivering vessels to be treated and a cleaning reactor to a PECVD coating apparatus.
  • the mechanism of FIG. 49 is usable with the vessel inspection apparatus of FIGS. 1, 9, 15, and 16, for example.
  • FIG. 50 is an exploded view of a two-piece syringe barrel and Luer lock fitting.
  • the syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-22, 26-28, 33-35, 37-39, 44, and 53-54.
  • FIG. 51 is an assembled view of the two-piece syringe barrel and Luer lock fitting of FIG. 50.
  • FIG. 52 is a view similar to FIG. 42 showing a syringe barrel being treated that has no flange or finger stops 440.
  • the syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-51, and 53-54.
  • FIG. 53 is a schematic view of an assembly for treating vessels. The assembly is usable with the apparatus of FIGS. 1-3, 8-9, 12-16, 18-22, 26-28, 33-35, and 37-49.
  • FIG. 54 is a diagrammatic view of the embodiment of FIG. 53.
  • FIG. 55 is a diagrammatic view similar to FIG. 2 of an embodiment of the invention including a plasma screen.
  • FIG. 56 is a schematic sectional view of an array of gas delivery tubes, having independent gas supplies and a mechanism for inserting and removing the gas delivery tubes from a vessel holder.
  • FIG. 57 is a plot of outgassing mass flow rate measured in Example 19.
  • FIG. 58 shows a linear rack, otherwise similar to FIG. 4.
  • FIG. 59 shows a schematic representation of a vessel processing system according to an exemplary embodiment of the present invention.
  • FIG. 60 shows a schematic representation of a vessel processing system according to another exemplary embodiment of the present invention.
  • FIG. 61 shows a processing station of a vessel processing system according to an exemplary embodiment of the present invention.
  • FIG. 62 shows a portable vessel holder according to an exemplary embodiment of the present invention.
  • Vessel processing system 94 Vacuum duct
  • Optical source transmission 112 Vessel holder (Fig. 3) station (defects) 114 Housing (of 50 or 112)
  • Vessel holder Exterior contact surface of
  • Vessel holder 120 Vessel holder (array)
  • Vessel holder 122 Vessel port (Fig. 4, 58)
  • Vessel holder 142 PECVD gas inlet port
  • Vacuum line (to 98)
  • Vessel holder 150 Flexible line (of 134)
  • RF radio frequency
  • First and “second” or similar references to, e.g., processing stations or processing devices refer to the minimum number of processing stations or devices that are present, but do not necessarily represent the order or total number of processing stations and devices. These terms do not limit the number of processing stations or the particular processing carried out at the respective stations.
  • an "organosilicon precursor” is a compound having at least one of the linkage:
  • a volatile organosilicon precursor defined as such a precursor that can be supplied as a vapor in a PECVD apparatus, is an optional organosilicon precursor.
  • the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors.
  • the invention has particular application to "contact surfaces" of medical devices and the like used or usable in contact with human or animal fluids or tissues, whether or not associated with a vessel.
  • a “vessel” in the context of the present invention can be any type of article that is adapted to contain or convey a material.
  • the material can be a liquid, a gas, a solid, or any two or more of these.
  • One example of a vessel is an article with at least one opening and a wall defining an interior contact surface.
  • at least a portion of the interior contact surface defines a "contact surface” which is treated according to the present disclosure.
  • the term “at least” in the context of the present invention means "equal or more" than the integer following the term.
  • a vessel in the context of the present invention has one or more openings.
  • One or two openings like the openings of a sample tube (one opening) or a syringe barrel (two openings) are preferred. If the vessel has two or more openings, they can be of same or different size. If there is more than one opening, one opening can be used for the gas inlet for a PECVD coating method according to the present invention, while the other openings are either capped or open.
  • a vessel according to the present invention can be a sample tube, e.g. for collecting or storing biological fluids like blood or urine, a syringe (or a part thereof, for example a syringe barrel) for storing or delivering a biologically active compound or composition, e.g. a medicament or pharmaceutical composition, a vial or ampoule for storing biological materials or biologically active compounds or compositions, a pipe, e.g. a catheter for transporting biological materials or biologically active compounds or compositions, or a cuvette for holding fluids, e.g. for holding biological materials or biologically active compounds or compositions.
  • a vessel can be of any shape.
  • a vessel has a substantially cylindrical wall adjacent to at least one of its open ends.
  • the interior wall of a vessel of this type is cylindrically shaped, like, e.g. in a sample tube or a syringe barrel.
  • Sample tubes and syringes or their parts for example syringe barrels
  • vials for example syringe barrels
  • petri dishes which commonly are generally cylindrical, are contemplated.
  • contemplated vessels include well or non- well slides or plates, for example titer plates or microtiter plates.
  • Still other non-limiting examples of contemplated vessels include pump contact surfaces in contact with the pumped material, including impeller contact surfaces, pump chamber contact surfaces and the like.
  • Even other non-limiting examples of contemplated vessels include parts of an fluid containment, pumping, processing, filtering, and delivery system, such as an intravenous fluid delivery system, a blood processing system (such as a heart-lung machine or a blood component separator) a dialysis system, or the body or insulin contacting surfaces of an insulin delivery system, as several examples.
  • vessels examples include tubing, pump interior contact surfaces, drug or saline containing bags or bottles, adapters and tubing connectors for connecting parts of the system together, intravenous needles and needle assemblies, membranes and filters, etc.
  • Other examples of vessels include measuring and delivery devices such as pipettes.
  • the invention has more general application to "contact surfaces" of medical devices and the like used or usable in contact with human or animal fluids or tissues, whether or not associated with a vessel.
  • Some additional non-limiting examples of devices having contact surfaces are devices inserted in an orifice, through the skin, or otherwise within the body of a human or animal, such as thermometers, probes, guide wires, catheters, electrical leads, surgical drains, pacemakers, defibrillators, stents, contact lenses, artificial lens replacements, corneal replacements, and other devices placed in contact with the eye, orthopedic devices such as screws, plates, and rods, clothing, face masks, eye shields, and other equipment worn by medical personnel, surgical drapes, sheet or fabric material used to make the same, surgical instruments such as saws and saw blades, drills and drill bits, etc.
  • the invention further has application to any contact surfaces of devices used or usable in contact with pharmaceutical preparations or other materials, such as ampoules, vials, syringes, bottles, bags, or other containment vessels, stirring rods, impellers, stirring pellets, etc., also within the definition of "contact surfaces.”
  • an ACL/PCL Reconstruction System an adapter, an adhesion barrier, an agar petri dish, an anesthesia unit, an anesthesia ventilator, an angiographic catheter, an ankle replacement, an aortic valve replacement, an apnea monitor, an applicator, an argon enhanced coagulation unit, an artificial facet replacement, an artificial heart, an artificial heart valve, an artificial organ, an artificial pacemaker, an artificial pancreas, an artificial urinary bladder, an aspirator, an atherectomy catheter, an auditory brainstem implant, an auto transfusion unit, a bag, a balloon catheter, a bare-metal stent, a beaker a bileaflet valve, a biliary stent, a bio implant, a bioceramic device, a bioresorbable stent, a biphasic cuirass ventilation, a blood culture device
  • implantable birth control device an O'Neil aspirating and irrigating needle, an O'Neil balloon infuser, an O'Neil intermittent urinary catheter, a contact lens, an orthopedic implant, an osseointegration implant, an oxinium replacement joint material, a pacemaker, a pacing Catheter, a pain management pump, a palatal obturator, a pancreatic Stent, a penile prosthesis, a penis enlargement device, a peripheral stent, a Peripherally Inserted Central Catheter (PICC), a peristaltic pump, a peritoneovenous shunt, a petri dish, a phonocardiograph, a phototherapy unit, a Pipette, a polyaxial screw, a port (medical), a portacaval shunt, a positive airway pressure device, a prepared media device, a pressure accessory or cable, a pressure transducer, a prostatic catheter, a
  • a “hydrophobic layer” in the context of the present invention means that the coating lowers the wetting tension of a surface coated with the coating, compared to the corresponding uncoated surface. Hydrophobicity is thus a function of both the uncoated substrate and the coating. The same applies with appropriate alterations for other contexts wherein the term “hydrophobic” is used.
  • the term “hydrophilic” means the opposite, i.e. that the wetting tension is increased compared to reference sample.
  • the present hydrophobic layers are primarily defined by their hydrophobicity and the process conditions providing hydrophobicity, and optionally can have a composition according to the empirical composition or sum formula SiwOxCyHz, for example where w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9, optionally where w is 1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is from 6 to about 9.
  • These values of w, x, y, and z are applicable to the empirical composition SiwOxCyHz throughout this specification.
  • the values of w, x, y, and z used throughout this specification should be understood as ratios or an empirical formula (e.g.
  • octamethylcyclotetrasiloxane which has the molecular composition Si404C8H24, can be described by the following empirical formula, arrived at by dividing each of w, x, y, and z in the molecular formula by 4, the largest common factor: Sil01C2H6.
  • the values of w, x, y, and z are also not limited to integers.
  • (acyclic) octamethyltrisiloxane, molecular composition S1 3 O 2 C 8 H 24 is reducible to SiiO 0 .67C2.67Hg.
  • wetting tension is a specific measure for the hydrophobicity or hydrophilicity of a surface.
  • An optional wetting tension measurement method in the context of the present invention is ASTM D 2578 or a modification of the method described in ASTM D 2578. This method uses standard wetting tension solutions (called dyne solutions) to determine the solution that comes nearest to wetting a plastic film surface for exactly two seconds. This is the film's wetting tension.
  • the procedure utilized is varied herein from ASTM D 2578 in that the substrates are not flat plastic films, but are tubes made according to the Protocol for Forming PET Tube and (except for controls) coated according to the Protocol for Coating Tube Interior with
  • a “lubricity layer” according to the present invention is a coating which has a lower frictional resistance than the uncoated surface. In other words, it reduces the frictional resistance of the coated surface in comparison to a reference surface which is uncoated.
  • the present lubricity layers are primarily defined by their lower frictional resistance than the uncoated surface and the process conditions providing lower frictional resistance than the uncoated surface, and optionally can have a composition according to the empirical composition SiwOxCyHz, as defined in this Definition Section. "Frictional resistance” can be static frictional resistance and/or kinetic frictional resistance.
  • One of the optional embodiments of the present invention is a syringe part, e.g.
  • the relevant static frictional resistance in the context of the present invention is the breakout force as defined herein
  • the relevant kinetic frictional resistance in the context of the present invention is the plunger sliding force as defined herein.
  • the plunger sliding force as defined and determined herein is suitable to determine the presence or absence and the lubricity characteristics of a lubricity layer in the context of the present invention whenever the coating is applied to any syringe or syringe part, for example to the inner wall of a syringe barrel.
  • the breakout force is of particular relevance for evaluation of the coating effect on a prefilled syringe, i.e. a syringe which is filled after coating and can be stored for some time, e.g. several months or even years, before the plunger is moved again (has to be "broken out").
  • the "plunger sliding force” in the context of the present invention is the force required to maintain movement of a plunger in a syringe barrel, e.g. during aspiration or dispense. It can advantageously be determined using the ISO 7886-1: 1993 test described herein and known in the art. A synonym for "plunger sliding force” often used in the art is “plunger force” or “pushing force”.
  • the "breakout force” in the context of the present invention is the initial force required to move the plunger in a syringe, for example in a prefilled syringe.
  • An "antimicrobially effective" treatment means that the treated surface has greater antimicrobial activity, measured by a recognized test method, than a control represented by the same surface that has not been antimicrobially treated.
  • a medical device or material or portion thereof comprising a contact surface.
  • a first treatment of SiO x , SiO x C y , or SiN x C y is applied to the contact surface.
  • a second, antimicrobially effective, treatment is applied to the contact surface with its first treatment.
  • the second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
  • the contact surface is defined in the definitions section above.
  • the precursor for the PECVD coating of the present invention is broadly defined as an organometallic precursor.
  • An organometallic precursor is defined in this specification as comprehending compounds of metal elements from Group III and/or Group IV of the Periodic Table having organic residues, e.g. hydrocarbon, aminocarbon or oxycarbon residues.
  • Organometallic compounds as presently defined include any precursor having organic moieties bonded to silicon or other Group III/ IV metal atoms directly, or optionally bonded through oxygen or nitrogen atoms.
  • the relevant elements of Group III of the Periodic Table are Boron, Aluminum, Gallium, Indium, Thallium, Scandium, Yttrium, and Lanthanum, Aluminum and Boron being preferred.
  • the relevant elements of Group IV of the Periodic Table are Silicon, Germanium, Tin, Lead, Titanium, Zirconium, Hafnium, and Thorium, with Silicon and Tin being preferred. Other volatile organic compounds can also be contemplated. However, organosilicon compounds are preferred for performing present invention.
  • organosilicon precursor is contemplated, where an "organosilicon precursor" is defined throughout this specification most broadly as a compound having at least one of the linkages:
  • the first structure immediately above is a tetravalent silicon atom connected to an oxygen atom and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom).
  • the second structure immediately above is a tetravalent silicon atom connected to an -NH- linkage and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom).
  • the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors. Also,
  • an oxygen-containing precursor e.g. a siloxane
  • a representative predicted empirical composition resulting from PECVD under conditions forming a hydrophobic or lubricating coating would be Si w O x C y H z as defined in the Definition Section, while a representative predicted empirical composition resulting from PECVD under conditions forming a barrier coating would be SiO x , where x in this formula is from about 1.5 to about 2.9.
  • a nitrogen- containing precursor e.g. a silazane
  • the predicted composition would be Si w* N x* C y* H z* , i.e.
  • Si w O x C y H z as specified in the Definition Section, O is replaced by N and the indices are adapted to the higher valency of N as compared to O (3 instead of 2).
  • the latter adaptation will generally follow the ratio of w, x, y and z in a siloxane to the corresponding indices in its aza counterpart.
  • Si w* N x* C y* H z* in which w*, x*, y*, and z* are defined the same as w, x, y, and z for the siloxane counterparts, but for an optional deviation in the number of hydrogen atoms.
  • One type of precursor starting material having the above empirical formula is a linear siloxane, for example a material having the following formula:
  • each R is independently selected from alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others, and n is 1, 2, 3, 4, or greater, optionally two or greater.
  • alkyl for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others
  • n is 1, 2, 3, 4, or greater, optionally two or greater.
  • HMDSO hexamethyldisiloxane
  • decamethyltetrasilazane or combinations of two or more of these.
  • V.C. Another type of precursor starting material is a monocyclic siloxane, for example a material having the following structural formula:
  • R is defined as for the linear structure and "a" is from 3 to about 10, or the analogous monocyclic silazanes.
  • a is from 3 to about 10
  • contemplated hetero-substituted and unsubstituted monocyclic siloxanes and silazanes include
  • V.C. Another type of precursor starting material is a polycyclic siloxane, for example a material having one of the following structural formulas:
  • Y can be oxygen or nitrogen
  • E is silicon
  • Z is a hydrogen atom or an organic substituent, for example alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.
  • Y oxygen
  • the respective structures from left to right, are a silatrane, a silquasilatrane, and a silproatrane.
  • Y is nitrogen
  • the respective structures are an azasilatrane, an azasilquasiatrane, and an azasilproatrane.
  • V.C. Another type of polycyclic siloxane precursor starting material is a
  • each R is a hydrogen atom or an organic substituent, for example alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.
  • alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.
  • SST-eMOl poly(methylsilsesquioxane) in which each R is methyl
  • SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane) in which 90% of the R groups are methyl, 10% are hydrogen atoms. This material is available in a 10% solution in tetrahydrofuran, for example. Combinations of two or more of these are also contemplated.
  • a contemplated precursor examples include methylsilatrane, CAS No. 2288-13-3, in which each Y is oxygen and Z is methyl, methylazasilatrane, SST-eMOl poly(methylsilsesquioxane), in which each R optionally can be methyl, SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which 90% of the R groups are methyl and 10% are hydrogen atoms, or a combination of any two or more of these.
  • V.C The analogous polysilsesquiazanes in which -NH- is substituted for the oxygen atom in the above structure are also useful for making analogous coatings.
  • contemplated polysilsesquiazanes are a poly(methylsilsesquiazane), in which each R is methyl, and a poly(Methyl-Hydridosilsesquiazane, in which 90% of the R groups are methyl, 10% are hydrogen atoms. Combinations of two or more of these are also contemplated.
  • V.C One particularly contemplated precursor for the lubricity layer according to the present invention is a monocyclic siloxane, for example is octamethylcyclotetrasiloxane.
  • One particularly contemplated precursor for the hydrophobic layer according to the present invention is a monocyclic siloxane, for example is octamethylcyclotetrasiloxane.
  • One particularly contemplated precursor for the barrier coating according to the present invention is a linear siloxane, for example is HMDSO.
  • the applying step optionally can be carried out by vaporizing the precursor and providing it in the vicinity of the substrate.
  • OMCTS is usually vaporized by heating it to about 50°C before applying it to the PECVD apparatus.
  • PECVD method In the context of the present invention, the following PECVD method is generally applied, which contains the following steps:
  • the coating characteristics are advantageously set by one or more of the following conditions: the plasma properties, the pressure under which the plasma is applied, the power applied to generate the plasma, the presence and relative amount of 0 2 in the gaseous reactant, the plasma volume, and the organosilicon precursor.
  • the coating is advantageously set by one or more of the following conditions: the plasma properties, the pressure under which the plasma is applied, the power applied to generate the plasma, the presence and relative amount of 0 2 in the gaseous reactant, the plasma volume, and the organosilicon precursor.
  • the coating characteristics are advantageously set by one or more of the following conditions: the plasma properties, the pressure under which the plasma is applied, the power applied to generate the plasma, the presence and relative amount of 0 2 in the gaseous reactant, the plasma volume, and the organosilicon precursor.
  • characteristics are set by the presence and relative amount of 0 2 in the gaseous reactant and/or the power applied to generate the plasma.
  • the plasma is in an optional aspect a non- hollow-cathode plasma.
  • the plasma is generated at reduced pressure (as compared to the ambient or atmospheric pressure).
  • the reduced pressure is less than 300 mTorr, optionally less than 200 mTorr, even optionally less than 100 mTorr.
  • the PECVD optionally is performed by energizing the gaseous reactant containing the precursor with electrodes powered at a frequency at microwave or radio frequency, and optionally at a radio frequency.
  • the radio frequency preferred to perform an embodiment of the invention will also be addressed as "RF frequency".
  • a typical radio frequency range for performing the present invention is a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz.
  • a frequency of 13.56 MHz is most preferred, this being a government sanctioned frequency for conducting PECVD work.
  • RF operates a lower power, there is less heating of the substrate/vessel. Because the focus of the present invention is putting a plasma coating on plastic substrates, lower processing temperature are desired to prevent melting/distortion of the substrate.
  • the microwave PECVD is applied in short bursts, by pulsing the power. The power pulsing extends the cycle time for the coating, which is undesired in the present invention.
  • the higher frequency microwave can also cause offgassing of volatile substances like residual water, oligomers and other materials in the plastic substrate. This offgassing can interfere with the PECVD coating.
  • a major concern with using microwave for PECVD is delamination of the coating from the substrate. Delamination occurs because the microwaves change the contact surface of the substrate prior to depositing the coating layer.
  • interface coating layers have been developed for microwave PECVD to achieve good bonding between the coating and the substrate. No such interface coating layer is needed with RF PECVD as there is no risk of delamination.
  • the lubricity layer and hydrophobic layer according to the present invention are advantageously applied using lower power. RF power operates at lower power and provides more control over the PECVD process than microwave power. Nonetheless, microwave power, though less preferred, is usable under suitable process conditions.
  • the lumen is the lumen of a vessel coated according to the present invention.
  • the RF power should scale with the volume of the vessel if the same electrode system is employed.
  • the power which has to be applied in order to achieve the same or a similar coating in a vessel of same geometry, but different size can easily be found.
  • the influence of the vessel geometry on the power to be applied is illustrated by the results of the Examples for tubes in comparison to the Examples for syringe barrels.
  • the plasma is generated with electrodes powered with sufficient power to form a coating on the substrate contact surface.
  • the plasma is optionally generated
  • the plasma is optionally generated (i) with electrodes supplied with an electric power of from 8 to 500 W, optionally from 20 to 400 W, optionally from 35 to 350 W, even optionally from 44 to 300 W, optionally from 44 to 70 W; and/or
  • the ratio of the electrode power to the plasma volume is equal or more than 5 W/ml, optionally is from 6 W/ml to 150 W/ml, optionally is from 7 W/ml to 100 W/ml, optionally from 7 W/ml to 20 W/ml.
  • the vessel geometry can also influence the choice of the gas inlet used for the PECVD coating.
  • a syringe can be coated with an open tube inlet, and a tube can be coated with a gas inlet having small holes which is extended into the tube.
  • the power (in Watts) used for PECVD also has an influence on the coating properties.
  • an increase of the power will increase the barrier properties of the coating, and a decrease of the power will increase the lubricity and hydrophobicity of the coating.
  • a power of less than 30 W will lead to a coating which is predominantly a barrier coating, while a power of more than 30 W will lead to a coating which is predominantly a lubricity layer (see Examples).
  • a further parameter determining the coating properties is the ratio of 0 2 (or another oxidizing agent) to the precursor (e.g. organosilicon precursor) in the gaseous reactant used for generating the plasma.
  • 0 2 or another oxidizing agent
  • the precursor e.g. organosilicon precursor
  • an increase of the 0 2 ratio in the gaseous reactant will increase the barrier properties of the coating, and a decrease of the 0 2 ratio will increase the lubricity and hydrophobicity of the coating.
  • 0 2 is optionally present in a volume-volume ratio to the gaseous reactant of from 0: 1 to 5: 1, optionally from 0: 1 to 1: 1, even optionally from 0: 1 to 0.5: 1 or even from 0: 1 to 0.1: 1.
  • the gaseous reactant should comprise less than 1 vol 0 2 , for example less than 0.5 vol 0 2 , and optionally is 0 2 -free. The same applies to a hydrophobic layer.
  • the 0 2 is optionally present in a volume : volume ratio to the gaseous reactant of from 1 : 1 to 100 : 1 in relation to the silicon containing precursor, optionally in a ratio of from 5 : 1 to 30 : 1, optionally in a ratio of from 10 : 1 to 20 : 1, even optionally in a ratio of 15 : 1.
  • V.A A specific embodiment is a method of applying a barrier coating of SiO x , defined in this specification (unless otherwise specified in a particular instance) as a coating containing silicon, oxygen, and optionally other elements, in which x, the ratio of oxygen to silicon atoms, is from about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2. These alternative definitions of x apply to any use of the term SiO x in this specification.
  • the barrier coating is applied to a contact surface, for example a sample collection tube, a syringe barrel, or another type of vessel. The method includes several steps.
  • V.A A vessel wall is provided, as is a reaction mixture comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas.
  • plasma forming gas i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas.
  • V.A. Plasma is formed in the reaction mixture that is substantially free of hollow cathode plasma.
  • the vessel wall is contacted with the reaction mixture, and the coating of SiO x is deposited on at least a portion of the vessel wall.
  • V.A the generation of a uniform plasma throughout the portion of the vessel to be coated is contemplated, as it has been found in certain instances to generate an SiO x coating providing a better barrier against oxygen.
  • Uniform plasma means regular plasma that does not include a substantial amount of hollow cathode plasma (which has a higher emission intensity than regular plasma and is manifested as a localized area of higher intensity interrupting the more uniform intensity of the regular plasma).
  • V.A The hollow cathode effect is generated by a pair of conductive contact surfaces opposing each other with the same negative potential with respect to a common anode. If the spacing is made (depending on the pressure and gas type) such that the space charge sheaths overlap, electrons start to oscillate between the reflecting potentials of the opposite wall sheaths leading to multiple collisions as the electrons are accelerated by the potential gradient across the sheath region. The electrons are confined in the space charge sheath overlap which results in very high ionization and high ion density plasmas. This phenomenon is described as the hollow cathode effect. Those skilled in the art are able to vary the processing conditions, such as the power level and the feed rates or pressure of the gases, to form uniform plasma throughout or to form plasma including various degrees of hollow cathode plasma.
  • microwave energy can be used to generate the plasma in a PECVD process.
  • the processing conditions can be different, however, as microwave energy applied to a thermoplastic vessel will excite (vibrate) water molecules. Since there is a small amount of water in all plastic materials, the microwaves will heat the plastic. As the plastic heats, the large driving force created by the vacuum inside of the device relative to atmospheric pressure outside the device will pull free or easily desorb materials to the interior contact surface 88 where they will either become volatile or will be weakly bound to the contact surface. The weakly bound materials will then create an interface that can hinder subsequent coatings (deposited from the plasma) from adhering to the plastic interior contact surface 88 of the device.
  • V.A As one way to negate this coating hindering effect, a coating can be deposited at very low power (in the example above 5 to 20 Watts at 2.45 GHz) creating a cap onto which subsequent coatings can adhere. This results in a two-step coating process (and two coating layers).
  • the initial gas flows for the capping layer
  • the capping layer can be changed to 2 seem ("standard cubic centimeters per minute") HMDSO and 20 seem oxygen with a process power of 5 to 20 Watts for approximately 2-10 seconds.
  • the gases can be adjusted to the flows in the example above and the power level increased to 20-50 Watts so that an SiO x coating, in which x in this formula is from about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6, alternatively about 2, can be deposited.
  • the capping layer might provide little to no functionality in certain embodiments, except to stop materials from migrating to the vessel interior contact surface 88 during the higher power SiO x coating deposition.
  • migration of easily desorbed materials in the device walls typically is not an issue at lower frequencies such as most of the RF range, since the lower frequencies do not excite (vibrate) molecular species.
  • the vessel 80 can be dried to remove embedded water before applying microwave energy. Desiccation or drying of the vessel 80 can be accomplished, for example, by thermally heating the vessel 80, as by using an electric heater or forced air heating. Desiccation or drying of the vessel 80 also can be accomplished by exposing the interior of the vessel 80, or gas contacting the interior of the vessel 80, to a desiccant. Other expedients for drying the vessel, such as vacuum drying, can also be used. These expedients can be carried out in one or more of the stations or devices illustrated or by a separate station or device.
  • V.A the coating hindering effect described above can be addressed by selection or processing of the resin from which the vessels 80 are molded to minimize the water content of the resin.
  • FIGS. 26 and 27 show a method and apparatus generally indicated at 290 for coating an inner contact surface 292 of a restricted opening 294 of a generally tubular vessel 250 to be processed, for example the restricted front opening 294 of a syringe barrel 250, by PECVD.
  • the previously described process is modified by connecting the restricted opening 294 to a processing vessel 296 and optionally making certain other modifications.
  • the generally tubular vessel 250 to be processed includes an outer contact surface 298, an inner or interior contact surface 254 defining a lumen 300, a larger opening 302 having an inner diameter, and a restricted opening 294 that is defined by an inner contact surface 292 and has an inner diameter smaller than the inner diameter of the larger opening 302.
  • the processing vessel 296 has a lumen 304 and a processing vessel opening 306, which optionally is the only opening, although in other embodiments a second opening can be provided that optionally is closed off during processing.
  • the processing vessel opening 306 is connected with the restricted opening 294 of the vessel 250 to be processed to establish communication between the lumen 300 of the vessel 250 to be processed and the processing vessel lumen via the restricted opening 294.
  • V.B At least a partial vacuum is drawn within the lumen 300 of the vessel 250 to be processed and lumen 304 of the processing vessel 296.
  • a PECVD reactant is flowed from the gas source 144 (see FIG. 7) through the first opening 302, then through the lumen 300 of the vessel 250 to be processed, then through the restricted opening 294, then into the lumen 304 of the processing vessel 296.
  • the PECVD reactant can be introduced through the larger opening 302 of the vessel 250 by providing a generally tubular inner electrode 308 having an interior passage 310, a proximal end 312, a distal end 314, and a distal opening 316, in an alternative embodiment multiple distal openings can be provided adjacent to the distal end 314 and communicating with the interior passage 310.
  • the distal end of the electrode 308 can be placed adjacent to or into the larger opening 302 of the vessel 250 to be processed.
  • a reactant gas can be fed through the distal opening 316 of the electrode 308 into the lumen 300 of the vessel 250 to be processed.
  • the reactant will flow through the restricted opening 294, then into the lumen 304, to the extent the PECVD reactant is provided at a higher pressure than the vacuum initially drawn before introducing the PECVD reactant.
  • V.B. Plasma 318 is generated adjacent to the restricted opening 294 under conditions effective to deposit a coating of a PECVD reaction product on the inner contact surface 292 of the restricted opening 294.
  • the plasma is generated by feeding RF energy to the generally U-shaped outer electrode 160 and grounding the inner electrode 308.
  • the feed and ground connections to the electrodes could also be reversed, though this reversal can introduce complexity if the vessel 250 to be processed, and thus also the inner electrode 308, are moving through the U-shaped outer electrode while the plasma is being generated.
  • the plasma 318 generated in the vessel 250 during at least a portion of processing can include hollow cathode plasma generated inside the restricted opening 294 and/or the processing vessel lumen 304.
  • the generation of hollow cathode plasma 318 can contribute to the ability to successfully apply a barrier coating at the restricted opening 294, although the invention is not limited according to the accuracy or applicability of this theory of operation.
  • the processing can be carried out partially under conditions generating a uniform plasma throughout the vessel 250 and the gas inlet, and partially under conditions generating a hollow cathode plasma, for example adjacent to the restricted opening 294.
  • the process is desirably operated under such conditions, as explained here and shown in the drawings, that the plasma 318 extends substantially throughout the syringe lumen 300 and the restricted opening 294.
  • the plasma 318 also desirably extends substantially throughout the syringe lumen 300, the restricted opening 294, and the lumen 304 of the processing vessel 296. This assumes that a uniform coating of the interior 254 of the vessel 250 is desired. In other embodiments non-uniform plasma can be desired.
  • the plasma 318 have a substantially uniform color throughout the syringe lumen 300 and the restricted opening 294 during processing, and optionally a substantially uniform color substantially throughout the syringe lumen 300, the restricted opening 294, and the lumen 304 of the processing vessel 296.
  • the plasma desirably is substantially stable throughout the syringe lumen 300 and the restricted opening 294, and optionally also throughout the lumen 304 of the processing vessel 296.
  • the restricted opening 294 has a first fitting 332 and the processing vessel opening 306 has a second fitting 334 adapted to seat to the first fitting 332 to establish communication between the lumen 304 of the processing vessel 296 and the lumen 300 of the vessel 250 to be processed.
  • the first and second fittings are male and female Luer lock fittings 332 and 334, respectively integral with the structure defining the restricted opening 294 and the processing vessel opening 306.
  • One of the fittings in this case the male Luer lock fitting 332, comprises a locking collar 336 with a threaded inner contact surface and defining an axially facing, generally annular first abutment 338 and the other fitting 334 comprises an axially facing, generally annular second abutment 340 facing the first abutment 338 when the fittings 332 and 334 are engaged.
  • a seal for example an O-ring 342 can be positioned between the first and second fittings 332 and 334.
  • an annular seal can be engaged between the first and second abutments 338 and 340.
  • the female Luer fitting 334 also includes dogs 344 that engage the threaded inner contact surface of the locking collar 336 to capture the O-ring 342 between the first and second fittings 332 and 334.
  • the communication established between the lumen 300 of the vessel 250 to be processed and the lumen 304 of the processing vessel 296 via the restricted opening 294 is at least substantially leak proof.
  • Luer lock fittings 332 and 334 can be made of electrically conductive material, for example stainless steel. This construction material forming or adjacent to the restricted opening 294 might contribute to formation of the plasma in the restricted opening 294.
  • the desirable volume of the lumen 304 of the processing vessel 296 is contemplated to be a trade-off between a small volume that will not divert much of the reactant flow away from the product contact surfaces desired to be coated and a large volume that will support a generous reactant gas flow rate through the restricted opening 294 before filling the lumen 304 sufficiently to reduce that flow rate to a less desirable value (by reducing the pressure difference across the restricted opening 294).
  • the contemplated volume of the lumen 304 in an embodiment, is less than three times the volume of the lumen 300 of the vessel 250 to be processed, or less than two times the volume of the lumen 300 of the vessel 250 to be processed, or less than the volume of the lumen 300 of the vessel 250 to be processed, or less than 50% of the volume of the lumen 300 of the vessel 250 to be processed, or less than 25% of the volume of the lumen 300 of the vessel 250 to be processed.
  • Other effective relationships of the volumes of the respective lumens are also contemplated.
  • the uniformity of coating can be improved in certain embodiments by repositioning the distal end of the electrode 308 relative to the vessel 250 so it does not penetrate as far into the lumen 300 of the vessel 250 as the position of the inner electrode shown in previous Figures.
  • the distal opening 316 can be positioned adjacent to the restricted opening 294, in other
  • the distal opening 316 can be positioned less than 7/8 the distance, optionally less than 3 ⁇ 4 the distance, optionally less than half the distance to the restricted opening 294 from the larger opening 302 of the vessel to be processed while feeding the reactant gas. Or, the distal opening 316 can be positioned less than 40%, less than 30%, less than 20%, less than 15%, less than 10%, less than 8%, less than 6%, less than 4%, less than 2%, or less than 1% of the distance to the restricted opening 294 from the larger opening of the vessel to be processed while feeding the reactant gas. [00162] V.B. Or, the distal end of the electrode 308 can be positioned either slightly inside or outside or flush with the larger opening 302 of the vessel 250 to be processed while
  • the positioning of the distal opening 316 relative to the vessel 250 to be processed can be optimized for particular dimensions and other conditions of treatment by testing it at various positions.
  • One particular position of the electrode 308 contemplated for treating syringe barrels 250 is with the distal end 314 penetrating about a quarter inch (about 6 mm) into the vessel lumen 300 above the larger opening 302.
  • the inventors presently contemplate that it is advantageous to place at least the distal end 314 of the electrode 308 within the vessel 250 so it will function suitably as an electrode, though that is not necessarily a requirement.
  • the plasma 318 generated in the vessel 250 can be made more uniform, extending through the restricted opening 294 into the processing vessel lumen 304, with less penetration of the electrode 308 into the lumen 300 than has previously been employed.
  • the distal end 314 of the electrode 308 commonly is placed closer to the closed end of the vessel than to its entrance.
  • the distal end 314 of the electrode 308 can be positioned at the restricted opening 294 or beyond the restricted opening 294, for example within the processing vessel lumen 304, as illustrated for example in FIG. 33.
  • Various expedients can optionally be provided, such as shaping the processing vessel 296 to improve the gas flow through the restricted opening 294.
  • the composite inner electrode and gas supply tube 398 can have distal gas supply openings such as 400, optionally located near the larger opening 302, and an extension electrode 402 extending distal of the distal gas supply openings 400, optionally extending to a distal end adjacent to the restricted opening 294, and optionally further extending into the processing vessel 324.
  • This construction is contemplated to facilitate formation of plasma within the inner contact surface 292 adjacent to the restricted opening 294.
  • the inner electrode 308, as in FIG. 26, can be moved during processing, for example, at first extending into the processing vessel lumen 304, then being withdrawn progressively proximally as the process proceeds.
  • This expedient is particularly contemplated if the vessel 250, under the selected processing conditions, is long, and movement of the inner electrode facilitates more uniform treatment of the interior contact surface 254.
  • the processing conditions such as the gas feed rate, the vacuum draw rate, the electrical energy applied to the outer electrode 160, the rate of withdrawing the inner electrode 308, or other factors can be varied as the process proceeds, customizing the process to different parts of a vessel to be treated.
  • the larger opening of the generally tubular vessel 250 to be processed can be placed on a vessel support 320, as by seating the larger opening 302 of the vessel 250 to be processed on a port 322 of the vessel support 320. Then the inner electrode 308 can be positioned within the vessel 250 seated on the vessel support 320 before drawing at least a partial vacuum within the lumen 300 of the vessel 250 to be processed.
  • the processing vessel 324 can be provided in the form of a conduit having a first opening 306 secured to the vessel 250 to be processed, as shown in FIG. 26, and a second opening 328 communicating with a vacuum port 330 in the vessel support 320.
  • the PECVD process gases can flow into the vessel 250, then via the restricted opening 294 into the processing vessel 324, then return via the vacuum port 330.
  • the vessel 250 can be evacuated through both openings 294 and 302 before applying the PECVD reactants.
  • an uncapped syringe barrel 250 can be provided with an interior coating of SiO x , in which x in this formula is from about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6, alternatively about 2, barrier or other type of PECVD coating by introducing the reactants from the source 144 through the opening at the back end 256 of the barrel 250 and drawing a vacuum using the vacuum source 98 drawing through the opening at the front end 260 of the barrel.
  • the vacuum source 98 can be connected through a second fitting 266 seated on the front end 260 of the syringe barrel 250.
  • the reactants can flow through the barrel 250 in a single direction (upward as shown in FIG. 22, though the orientation is not critical), and there is no need to convey the reactants through a probe that separates the fed gas from the exhausted gas within the syringe barrel 250.
  • the front and back ends 260 and 256 of the syringe barrel 250 can also be reversed relative to the coating apparatus, in an alternative arrangement.
  • the probe 108 can act simply as an electrode, and can either be tubular or a solid rod in this embodiment. As before, the separation between the interior contact surface 254 and the probe 108 can be uniform over at least most of the length of the syringe barrel 250.
  • FIG. 37 is a view similar to FIG. 22 showing another embodiment in which the fitting 266 is independent of and not attached to the plate electrodes 414 and 416.
  • the fitting 266 can have a Luer lock fitting adapted to be secured to the corresponding fitting of the syringe barrel 250. This embodiment allows the vacuum conduit 418 to pass over the electrode 416 while the vessel holder 420 and attached vessel 250 move between the electrodes 414 and 416 during a coating step.
  • FIG. 38 is a view similar to FIG. 22 showing still another embodiment in which the front end 260 of the syringe barrel 250 is open and the syringe barrel 250 is enclosed by a vacuum chamber 422 seated on the vessel holder 424.
  • the pressures PI within the syringe barrel 250 and within the vacuum chamber 422 are approximately identical, and the vacuum in the vacuum chamber 422 optionally is drawn through the front end 260 of the syringe barrel 250.
  • the process gases flow into the syringe barrel 250, they flow through the front end 260 of the syringe barrel 250 until a steady composition is provided within the syringe barrel 250, at which time the electrode 160 is energized to form the coating.
  • FIG. 39 is a view similar to FIG. 22 showing yet another embodiment in which the back flange of the syringe barrel 250 is clamped between a vessel holder 428 and an electrode assembly 430 to which a cylindrical electrode or pair of plate electrodes indicated as 160 and a vacuum source 98 are secured.
  • the volume generally indicated as 432 enclosed outside the syringe barrel 250 is relatively small in this embodiment to minimize the pumping needed to evacuate the volume 432 and the interior of the syringe barrel 250 to operate the PECVD process.
  • FIG. 40 is a view similar to FIG. 22 and FIG. 41 is a plan view showing even another embodiment as an alternative to FIG.
  • PI can be a lower vacuum, i.e. a higher pressure than P2 during a PECVD process so the waste process gases and by-products will pass through the front end 260 of the syringe barrel 250 and be exhausted.
  • a separate vacuum chamber conduit 436 to serve the vacuum chamber 422 allows the use of a separate vacuum pump to evacuate the greater enclosed volume 432 more quickly.
  • FIG. 41 is a plan view of the embodiment of FIG. 40, also showing the electrode 160 removed from FIG. 40.
  • V.C. Another embodiment is a method of applying a lubricity layer derived from an organosilicon precursor.
  • a "lubricity layer” or any similar term is generally defined as a coating that reduces the frictional resistance of the coated contact surface, relative to the uncoated contact surface. If the coated object is a syringe (or syringe part, e.g. syringe barrel) or any other item generally containing a plunger or movable part in sliding contact with the coated contact surface, the frictional resistance has two main aspects - breakout force and plunger sliding force.
  • the plunger sliding force test is a specialized test of the coefficient of sliding friction of the plunger within a syringe, accounting for the fact that the normal force associated with a coefficient of sliding friction as usually measured on a flat contact surface is addressed by standardizing the fit between the plunger or other sliding element and the tube or other vessel within which it slides.
  • the parallel force associated with a coefficient of sliding friction as usually measured is comparable to the plunger sliding force measured as described in this specification.
  • Plunger sliding force can be measured, for example, as provided in the ISO 7886- 1: 1993 test.
  • the plunger sliding force test can also be adapted to measure other types of frictional resistance, for example the friction retaining a stopper within a tube, by suitable variations on the apparatus and procedure.
  • the plunger can be replaced by a closure and the withdrawing force to remove or insert the closure can be measured as the counterpart of plunger sliding force.
  • the breakout force can be measured.
  • the breakout force is the force required to start a stationary plunger moving within a syringe barrel, or the comparable force required to unseat a seated, stationary closure and begin its movement.
  • the breakout force is measured by applying a force to the plunger that starts at zero or a low value and increases until the plunger begins moving.
  • the breakout force tends to increase with storage of a syringe, after the prefilled syringe plunger has pushed away the intervening lubricant or adhered to the barrel due to decomposition of the lubricant between the plunger and the barrel.
  • the breakout force is the force needed to overcome "sticktion," an industry term for the adhesion between the plunger and barrel that needs to be overcome to break out the plunger and allow it to begin moving.
  • V.C Some utilities of coating a vessel in whole or in part with a lubricity layer, such as selectively at contact surfaces contacted in sliding relation to other parts, is to ease the insertion or removal of a stopper or passage of a sliding element such as a piston in a syringe or a stopper in a sample tube.
  • the vessel can be made of glass or a polymer material such as polyester, for example polyethylene terephthalate (PET), a cyclic olefin copolymer (COC), an olefin such as polypropylene, or other materials.
  • Applying a lubricity layer by PECVD can avoid or reduce the need to coat the vessel wall or closure with a sprayed, dipped, or otherwise applied organosilicon or other lubricant that commonly is applied in a far larger quantity than would be deposited by a PECVD process.
  • V.C In any of the above embodiments V.C, a plasma, optionally a non-hollow- cathode plasma, optionally can be formed in the vicinity of the substrate
  • the precursor optionally can be provided in the substantial absence of oxygen.
  • V.C. In any of embodiments V.C, the precursor optionally can be provided in the substantial absence of a carrier gas.
  • V.C. In any of embodiments V.C, in which the precursor optionally can be provided in the substantial absence of nitrogen.
  • V.C. In any of embodiments V.C, in which the precursor optionally can be provided at less than 1 Torr absolute pressure.
  • the precursor optionally can be provided to the vicinity of a plasma emission.
  • the coating optionally can be applied to the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm, or 10-200 nm, or 20 to 100 nm thick.
  • the thickness of this and other coatings can be measured, for example, by transmission electron microscopy (TEM).
  • the TEM can be carried out, for example, as follows.
  • Samples can be prepared for Focused Ion Beam (FIB) cross-sectioning in two ways. Either the samples can be first coated with a thin layer of carbon (50-100nm thick) and then coated with a sputtered layer of platinum (50-100nm thick) using a K575X Emitech coating system, or the samples can be coated directly with the protective sputtered Pt layer.
  • the coated samples can be placed in an FEI FIB200 FIB system.
  • An additional layer of platinum can be FIB-deposited by injection of an oregano- metallic gas while rastering the 30kV gallium ion beam over the area of interest.
  • the area of interest for each sample can be chosen to be a location half way down the length of the syringe barrel.
  • Thin cross sections measuring approximately 15 ⁇ ("micrometers") long, 2 ⁇ wide and 15 ⁇ deep can be extracted from the die contact surface using a proprietary in-situ FIB lift-out technique.
  • the cross sections can be attached to a 200 mesh copper TEM grid using FIB- deposited platinum.
  • One or two windows in each section, measuring ⁇ 8 ⁇ wide, can be thinned to electron transparency using the gallium ion beam of the FEI FIB.
  • V.C. Cross-sectional image analysis of the prepared samples can be performed utilizing either a Transmission Electron Microscope (TEM), or a Scanning Transmission
  • STEM Electron Microscope
  • V.C For TEM analysis the sample grids can be transferred to a Hitachi HF2000 transmission electron microscope. Transmitted electron images can be acquired at appropriate magnifications. The relevant instrument settings used during image acquisition can be those given below.
  • the substrate can comprise glass or a polymer, for example a polycarbonate polymer, an olefin polymer, a cyclic olefin copolymer, a polypropylene polymer, a polyester polymer, a polyethylene terephthalate polymer or a combination of any two or more of these.
  • a polymer for example a polycarbonate polymer, an olefin polymer, a cyclic olefin copolymer, a polypropylene polymer, a polyester polymer, a polyethylene terephthalate polymer or a combination of any two or more of these.
  • the PECVD optionally can be performed by energizing the gaseous reactant containing the precursor with electrodes powered at a RF frequency as defined above, for example a frequency from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • a RF frequency as defined above, for example a frequency from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • the plasma can be generated by energizing the gaseous reactant comprising the precursor with electrodes supplied with electric power sufficient to form a lubricity layer.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W.
  • the ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml.
  • These power levels are suitable for applying lubricity coatings to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
  • V.C One contemplated product optionally can be a syringe having a barrel treated by the method of any one or more of embodiments V.C.
  • a suitable barrier or other type of coating usable in conjunction with PECVD-applied coatings or other PECVD treatment as disclosed here, can be a liquid barrier, lubricant, contact surface energy tailoring, or other type of coating 90 applied to the interior contact surface of a vessel, either directly or with one or more intervening PECVD- applied coatings described in this specification, for example SiO x , a lubricity layer characterized as defined in the Definition Section, or both.
  • Suitable liquid barriers or other types of coatings 90 also optionally can be applied, for example, by applying a liquid monomer or other polymerizable or curable material to the interior contact surface of the vessel 80 and curing, polymerizing, or crosslinking the liquid monomer to form a solid polymer.
  • Suitable liquid barrier or other types of coatings 90 can also be provided by applying a solvent-dispersed polymer to the contact surface 88 and removing the solvent.
  • V.D Either of the above methods can include as a step forming a coating 90 on the interior 88 of a vessel 80 via the vessel port 92 at a processing station or device 28.
  • a liquid coating for example of a curable monomer, prepolymer, or polymer dispersion
  • PVdC acrylic and polyvinylidene chloride
  • V.D Either of the above methods can also or include as a step forming a coating on the exterior outer wall of a vessel 80.
  • the coating optionally can be a barrier coating, optionally an oxygen barrier coating, or optionally a water barrier coating.
  • a suitable coating is polyvinylidene chloride, which functions both as a water barrier and an oxygen barrier.
  • the barrier coating can be applied as a water-based coating.
  • the coating optionally can be applied by dipping the vessel in it, spraying it on the vessel, or other expedients.
  • a vessel having an exterior barrier coating as described above is also contemplated.
  • barrier coating 90 (shown in FIG. 2, for example), which can be an SiO x coating applied to a thickness of at least 2 nm, or at least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at least 700 nm, or at least 800 nm, or at least 900 nm.
  • the coating can be up to 1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most 500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or at most 100 nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nm thick.
  • the thickness of the SiO x or other coating can be measured, for example, by transmission electron microscopy (TEM), and its composition can be measured by X-ray photoelectron spectroscopy (XPS).
  • TEM transmission electron microscopy
  • XPS X-ray photoelectron spectroscopy
  • Oxygen transmission is affected by the physical features of the coating, such as its thickness, the presence of cracks, and other physical details of the coating.
  • the concentration ratio of organic moieties (carbon and hydrogen compounds) to OH moieties in the deposited coating can be increased. This can be done, for example, by increasing the proportion of oxygen in the feed gases (as by increasing the oxygen feed rate or by lowering the feed rate of one or more other constituents). The lowered incidence of OH moieties is believed to result from increasing the degree of reaction of the oxygen feed with the hydrogen in the silicone source to yield more volatile water in the PECVD exhaust and a lower
  • Distortion of the medical devices can be reduced or eliminated by employing the energy in a series of two or more pulses separated by cooling time, by cooling the vessels while applying energy, by applying the coating in a shorter time (commonly thus making it thinner), by selecting a frequency of the applied coating that is absorbed minimally by the base material selected for being coated, and/or by applying more than one coating, with time in between the respective energy application steps.
  • high power pulsing can be used with a duty cycle of 1 millisecond on, 99 milliseconds off, while continuing to feed the process gas. The process gas is then the coolant, as it keeps flowing between pulses.
  • Another alternative is to reconfigure the power applicator, as by adding magnets to confine the plasma increase the effective power application (the power that actually results in incremental coating, as opposed to waste power that results in heating or unwanted coating). This expedient results in the application of more coating-formation energy per total Watt-hour of energy applied. See for example U.S. Patent 5,904,952.
  • An oxygen post-treatment of the coating can be applied to remove OH moieties from the previously-deposited coating. This treatment is also contemplated to remove residual volatile organosilicon compounds or silicones or oxidize the coating to form additional SiO x .
  • the plastic base material tube can be preheated.
  • a different volatile source of silicon such as hexamethyldisilazane (HMDZ)
  • HMDZ hexamethyldisilazane
  • changing the feed gas to HMDZ will address the problem because this compound has no oxygen moieties in it, as supplied.
  • one source of OH moieties in the HMDSO-sourced coating is hydrogenation of at least some of the oxygen atoms present in unreacted HMDSO.
  • a composite coating can be used, such as a carbon-based coating combined with SiO x . This can be done, for example, by changing the reaction conditions or by adding a substituted or unsubstituted hydrocarbon, such as an alkane, alkene, or alkyne, to the feed gas as well as an organosilicon-based compound. See for example U.S. Patent 5,904,952, which states in relevant part: "For example, inclusion of a lower hydrocarbon such as propylene provides carbon moieties and improves most properties of the deposited films (except for light transmission), and bonding analysis indicates the film to be silicon dioxide in nature. Use of methane, methanol, or acetylene, however, produces films that are silicone in nature.
  • the inclusion of a minor amount of gaseous nitrogen to the gas stream provides nitrogen moieties in the deposited films and increases the deposition rate, improves the transmission and reflection optical properties on glass, and varies the index of refraction in response to varied amounts of N 2 .
  • the addition of nitrous oxide to the gas stream increases the deposition rate and improves the optical properties, but tends to decrease the film hardness.”
  • a diamond-like carbon (DLC) coating can be formed as the primary or sole coating deposited. This can be done, for example, by changing the reaction conditions or by feeding methane, hydrogen, and helium to a PECVD process. These reaction feeds have no oxygen, so no OH moieties can be formed.
  • an SiO x coating can be applied on the interior of a tube or syringe barrel and an outer DLC coating can be applied on the exterior contact surface of a tube or syringe barrel.
  • the SiO x and DLC coatings can both be applied as a single layer or plural layers of an interior tube or syringe barrel coating.
  • the barrier or other type of coating 90 reduces the transmission of atmospheric gases into the vessel 80 through its interior contact surface 88. Or, the barrier or other type of coating 90 reduces the contact of the contents of the vessel 80 with the interior contact surface 88.
  • the barrier or other type of coating can comprise, for example, SiO x , amorphous (for example, diamond-like) carbon, or a combination of these.
  • Any coating described herein can be used for coating a contact surface, for example a plastic contact surface. It can further be used as a barrier layer, for example as a barrier against a gas or liquid, optionally against water vapor, oxygen and/or air.
  • It can also be used for preventing or reducing mechanical and/or chemical effects which the coated contact surface would have on a compound or composition if the contact surface were uncoated. For example, it can prevent or reduce the precipitation of a compound or composition, for example insulin precipitation or blood clotting or platelet activation.
  • the illustrated vessel 80 can be generally tubular, having an opening 82 at one end of the vessel, opposed by a closed end 84.
  • the vessel 80 also has a wall 86 defining an interior contact surface 88.
  • a medical sample tube such as an evacuated blood collection tube, as commonly is used by a phlebotomist for receiving a venipuncture sample of a patient's blood for use in a medical laboratory.
  • the vessel 80 can be made, for example, of thermoplastic material.
  • suitable thermoplastic material are polyethylene terephthalate or a polyolefin such as polypropylene or a cyclic polyolefin copolymer.
  • the vessel 80 can be made by any suitable method, such as by injection molding, by blow molding, by machining, by fabrication from tubing stock, or by other suitable means. PECVD can be used to form a coating on the internal contact surface of SiO x .
  • the vessel 80 desirably can be strong enough to withstand a substantially total internal vacuum substantially without deformation when exposed to an external pressure of 760 Torr or atmospheric pressure and other coating processing conditions.
  • This property can be provided, in a thermoplastic vessel 80, by providing a vessel 80 made of suitable materials having suitable dimensions and a glass transition temperature higher than the processing temperature of the coating process, for example a cylindrical wall 86 having sufficient wall thickness for its diameter and material.
  • VH.A. l. Medical vessels or containers like sample collection tubes and syringes are relatively small and are injection molded with relatively thick walls, which renders them able to be evacuated without being crushed by the ambient atmospheric pressure. They are thus stronger than carbonated soft drink bottles or other larger or thinner- walled plastic containers. Since sample collection tubes designed for use as evacuated vessels typically are constructed to withstand a full vacuum during storage, they can be used as vacuum chambers.
  • Vn.A. l Such adaptation of the vessels to be their own vacuum chambers might eliminate the need to place the vessels into a vacuum chamber for PECVD treatment, which typically is carried out at very low pressure.
  • the use of a vessel as its own vacuum chamber can result in faster processing time (since loading and unloading of the parts from a separate vacuum chamber is not necessary) and can lead to simplified equipment configurations.
  • a vessel holder is contemplated, for certain embodiments, that will hold the device (for alignment to gas tubes and other apparatus), seal the device (so that the vacuum can be created by attaching the vessel holder to a vacuum pump) and move the device between molding and subsequent processing steps.
  • a vessel 80 used as an evacuated blood collection tube should be able to withstand external atmospheric pressure, while internally evacuated to a reduced pressure useful for the intended application, without a substantial volume of air or other atmospheric gas leaking into the tube (as by bypassing the closure) or permeating through the wall 86 during its shelf life. If the as-molded vessel 80 cannot meet this requirement, it can be processed by coating the interior contact surface 88 with a barrier or other type of coating 90. It is desirable to treat and/or coat the interior contact surfaces of these devices (such as sample collection tubes and syringe barrels) to impart various properties that will offer advantages over existing polymeric devices and/or to mimic existing glass products. It is also desirable to measure various properties of the devices before and/or after treatment or coating.
  • VILA.1.a A process is contemplated for applying a lubricity layer characterized as defined in the Definition Section on a substrate, for example the interior of the barrel of a syringe, comprising applying one of the described precursors on or in the vicinity of a substrate at a thickness of 1 to 5000 nm, optionally 10 to 1000 nm, optionally 10-200 nm, optionally 20 to 100 nm thick and crosslinking or polymerizing (or both) the coating, optionally in a PECVD process, to provide a lubricated contact surface.
  • the coating applied by this process is also contemplated to be new.
  • a coating of Si w O x C y H z as defined in the Definition Section can have utility as a hydrophobic layer. Coatings of this kind are contemplated to be hydrophobic, independent of whether they function as lubricity layers. A coating or treatment is defined as "hydrophobic" if it lowers the wetting tension of a contact surface, compared to the
  • Hydrophobicity is thus a function of both the untreated substrate and the treatment.
  • the degree of hydrophobicity of a coating can be varied by varying its composition, properties, or deposition method. For example, a coating of SiOx having little or no hydrocarbon content is more hydrophilic than a coating of Si w O x C y H z as defined in the Definition Section. Generally speaking, the higher the C-H x (e.g. CH, CH 2 , or CH 3 ) moiety content of the coating, either by weight, volume, or molarity, relative to its silicon content, the more hydrophobic the coating.
  • C-H x e.g. CH, CH 2 , or CH 3
  • a hydrophobic layer can be very thin, having a thickness of at least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at least 700 nm, or at least 800 nm, or at least 900 nm.
  • the coating can be up to 1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most 500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or at most 100 nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nm thick. Specific thickness ranges composed of any one of the minimum thicknesses expressed above, plus any equal or greater one of the maximum thicknesses expressed above, are expressly contemplated.
  • VILA.1.a One utility for such a hydrophobic layer is to isolate a thermoplastic tube wall, made for example of polyethylene terephthalate (PET), from blood collected within the tube.
  • the hydrophobic layer can be applied on top of a hydrophilic SiO x coating on the internal contact surface of the tube.
  • the SiO x coating increases the barrier properties of the thermoplastic tube and the hydrophobic layer changes the contact surface energy of blood contact surface with the tube wall.
  • the hydrophobic layer can be made by providing a precursor selected from those identified in this specification.
  • the hydrophobic layer precursor can comprise hexamethyldisiloxane (HMDSO), octamethylcyclotetrasiloxane (OMCTS), or
  • TMDSO tetramethyldisiloxane
  • VILA.1.a Another use for a hydrophobic layer is to prepare a glass cell preparation tube.
  • the tube has a wall defining a lumen, a hydrophobic layer in the internal contact surface of the glass wall, and contains a citrate reagent.
  • the hydrophobic layer can be made by providing a precursor selected from those identified elsewhere in this specification.
  • the hydrophobic layer precursor can comprise hexamethyldisiloxane (HMDSO) or
  • OCTS octamethylcyclotetrasiloxane
  • R is a hydrogen atom or an organic substituent, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, epoxide, or others. Combinations of two or more of these are also contemplated.
  • VILA.1. Combinations of acid or base catalysis and heating, using an alkyl trimethoxysilane precursor as described above, can condense the precursor (removing ROH byproducts) to form crosslinked polymers, which can optionally be further crosslinked via an alternative method.
  • One specific example is by Shimojima et. al. J. Mater. Chem., 2007, 17, 658 - 663.
  • a lubricity layer characterized as defined in the Definition Section, can be applied as a subsequent coating after applying an SiO x barrier coating to the interior contact surface 88 of the vessel 80 to provide a lubricity layer, particularly if the lubricity layer is a liquid organosiloxane compound at the end of the coating process.
  • VILA.1.a after the lubricity layer is applied, it can be post-cured after the PECVD process. Radiation curing approaches, including UV-initiated (free radial or cationic), electron-beam (E-beam), and thermal as described in Development Of Novel Cycloaliphatic Siloxanes For Thermal And UV-Curable Applications (Ruby Chakraborty Dissertation, can 2008) be utilized.
  • UV-initiated free radial or cationic
  • E-beam electron-beam
  • thermal as described in Development Of Novel Cycloaliphatic Siloxanes For Thermal And UV-Curable Applications (Ruby Chakraborty Dissertation, can 2008) be utilized.
  • VILA.1.a. Another approach for providing a lubricity layer is to use a silicone demolding agent when injection-molding the thermoplastic vessel to be lubricated.
  • a silicone demolding agent when injection-molding the thermoplastic vessel to be lubricated.
  • any of the demolding agents and latent monomers causing in-situ thermal lubricity layer formation during the molding process can be used.
  • the aforementioned monomers can be doped into traditional demolding agents to accomplish the same result.
  • a lubricity layer characterized as defined in the Definition Section, is particularly contemplated for the internal contact surface of a syringe barrel as further described below.
  • a lubricated internal contact surface of a syringe barrel can reduce the plunger sliding force needed to advance a plunger in the barrel during operation of a syringe, or the breakout force to start a plunger moving after the prefilled syringe plunger has pushed away the intervening lubricant or adhered to the barrel, for example due to decomposition of the lubricant between the plunger and the barrel.
  • a lubricity layer also can be applied to the interior contact surface 88 of the vessel 80 to improve adhesion of a subsequent coating of SiO x .
  • the coating 90 can comprise a layer of SiO x and a lubricity layer and/or hydrophobic layer, characterized as defined in the Definition Section.
  • the lubricity layer and/or hydrophobic layer of Si w O x C y H z can be deposited between the layer of SiO x and the interior contact surface of the vessel.
  • the layer of SiO x can be deposited between the lubricity layer and/or hydrophobic layer and the interior contact surface of the vessel.
  • three or more layers, either alternating or graduated between these two coating compositions: (1) a layer of SiO x and (2) the lubricity layer and/or hydrophobic layer; can also be used.
  • the layer of SiO x can be deposited adjacent to the lubricity layer and/or hydrophobic layer or remotely, with at least one intervening layer of another material.
  • the layer of SiO x can be deposited adjacent to the interior contact surface of the vessel.
  • the lubricity layer and/or hydrophobic layer can be deposited adjacent to the interior contact surface of the vessel.
  • VILA.1.a Another expedient contemplated here, for adjacent layers of SiO x and a lubricity layer and/or hydrophobic layer, is a graded composite of Si w O x C y H z , as defined in the Definition Section.
  • a graded composite can be separate layers of a lubricity layer and/or hydrophobic layer and SiO x with a transition or interface of intermediate composition between them, or separate layers of a lubricity layer and/or hydrophobic layer and SiO x with an intermediate distinct layer of intermediate composition between them, or a single layer that changes continuously or in steps from a composition of a lubricity layer and/or hydrophobic layer to a composition more like SiO x , going through the coating in a normal direction.
  • the grade in the graded composite can go in either direction.
  • the a lubricity layer and/or hydrophobic layer can be applied directly to the substrate and graduate to a composition further from the contact surface of SiO x .
  • the composition of SiO x can be applied directly to the substrate and graduate to a composition further from the contact surface of a lubricity layer and/or hydrophobic layer.
  • a graduated coating is particularly contemplated if a coating of one composition is better for adhering to the substrate than the other, in which case the better-adhering composition can, for example, be applied directly to the substrate.
  • the more distant portions of the graded coating can be less compatible with the substrate than the adjacent portions of the graded coating, since at any point the coating is changing gradually in properties, so adjacent portions at nearly the same depth of the coating have nearly identical composition, and more widely physically separated portions at substantially different depths can have more diverse properties. It is also contemplated that a coating portion that forms a better barrier against transfer of material to or from the substrate can be directly against the substrate, to prevent the more remote coating portion that forms a poorer barrier from being contaminated with the material intended to be barred or impeded by the barrier.
  • VILA.1. The coating, instead of being graded, optionally can have sharp transitions between one layer and the next, without a substantial gradient of composition. Such coatings can be made, for example, by providing the gases to produce a layer as a steady state flow in a non- plasma state, then energizing the system with a brief plasma discharge to form a coating on the substrate. If a subsequent coating is to be applied, the gases for the previous coating are cleared out and the gases for the next coating are applied in a steady-state fashion before energizing the plasma and again forming a distinct layer on the contact surface of the substrate or its outermost previous coating, with little if any gradual transition at the interface.
  • VILA.l.b Citrate Blood Tube Having Wall Coated With Hydrophobic layer Deposited from an Organosilicon Precursor
  • VILA.1.b Another embodiment is a cell preparation tube having a wall provided with a hydrophobic layer on its inside contact surface and containing an aqueous sodium citrate reagent.
  • the hydrophobic layer can be also be applied on top of a hydrophilic SiO x coating on the internal contact surface of the tube.
  • the SiO x coating increases the barrier properties of the thermoplastic tube and the hydrophobic layer changes the contact surface energy of blood contact surface with the tube wall.
  • VILA. l.b. The wall is made of thermoplastic material having an internal contact surface defining a lumen.
  • a blood collection tube according to the embodiment VILA.1.b can have a first layer of SiO x on the internal contact surface of the tube, applied as explained in this specification, to function as an oxygen barrier and extend the shelf life of an evacuated blood collection tube made of thermoplastic material.
  • a second layer of a hydrophobic layer, characterized as defined in the Definition Section, can then be applied over the barrier layer on the internal contact surface of the tube to provide a hydrophobic contact surface.
  • the coating is effective to reduce the platelet activation of blood plasma treated with a sodium citrate additive and exposed to the inner contact surface, compared to the same type of wall uncoated.
  • VILA.1.b. PECVD is used to form a hydrophobic layer on the internal contact surface, characterized as defined in the Definition Section. Unlike conventional citrate blood collection tubes, the blood collection tube having a hydrophobic layer, characterized as defined in the Definition Section does not require a coating of baked on silicone on the vessel wall, as is conventionally applied to make the contact surface of the tube hydrophobic.
  • VILA. l.b. Both layers can be applied using the same precursor, for example HMDSO or OMCTS, and different PECVD reaction conditions.
  • VILA.1.b A sodium citrate anticoagulation reagent is then placed within the tube and it is evacuated and sealed with a closure to produce an evacuated blood collection tube.
  • the components and formulation of the reagent are known to those skilled in the art.
  • the aqueous sodium citrate reagent is disposed in the lumen of the tube in an amount effective to inhibit coagulation of blood introduced into the tube.
  • VILA.l.c SiO x Barrier Coated Double Wall Plastic Vessel- COC, PET, SiO x layers
  • VILA.1.c Another embodiment is a vessel having a wall at least partially enclosing a lumen.
  • the wall has an interior polymer layer enclosed by an exterior polymer layer.
  • One of the polymer layers is a layer at least 0.1 mm thick of a cyclic olefin copolymer (COC) resin defining a water vapor barrier.
  • Another of the polymer layers is a layer at least 0.1 mm thick of a polyester resin.
  • the wall includes an oxygen barrier layer of SiO x having a thickness of from about 10 to about 500 angstroms.
  • the vessel 80 can be a double- walled vessel having an inner wall 408 and an outer wall 410, respectively made of the same or different materials.
  • One particular embodiment of this type can be made with one wall molded from a cyclic olefin copolymer (COC) and the other wall molded from a polyester such as polyethylene terephthalate (PET), with an SiO x coating as previously described on the interior contact surface 412.
  • COC cyclic olefin copolymer
  • PET polyethylene terephthalate
  • SiO x coating as previously described on the interior contact surface 412.
  • a tie coating or layer can be inserted between the inner and outer walls to promote adhesion between them.
  • the inner wall 408 can be made of PET coated on the interior contact surface 412 with an SiO x barrier layer, and the outer wall 410 can be made of COC.
  • PET coated with SiO x is an excellent oxygen barrier, while COC is an excellent barrier for water vapor, providing a low water vapor transition rate (WVTR).
  • WVTR water vapor transition rate
  • This composite vessel can have superior barrier properties for both oxygen and water vapor.
  • This construction is contemplated, for example, for an evacuated medical sample collection tube that contains an aqueous reagent as manufactured, and has a substantial shelf life, so it should have a barrier preventing transfer of water vapor outward or transfer of oxygen or other gases inward through its composite wall during its shelf life.
  • the inner wall 408 can be made of COC coated on the interior contact surface 412 with an SiO x barrier layer, and the outer wall 410 can be made of PET.
  • This construction is contemplated, for example, for a prefilled syringe that contains an aqueous sterile fluid as manufactured.
  • the SiO x barrier will prevent oxygen from entering the syringe through its wall.
  • the COC inner wall will prevent ingress or egress of other materials such as water, thus preventing the water in the aqueous sterile fluid from leaching materials from the wall material into the syringe.
  • the COC inner wall is also contemplated to prevent water derived from the aqueous sterile fluid from passing out of the syringe (thus undesirably concentrating the aqueous sterile fluid), and will prevent non-sterile water or other fluids outside the syringe from entering through the syringe wall and causing the contents to become non- sterile.
  • the COC inner wall is also contemplated to be useful for decreasing the breaking force or friction of the plunger against the inner wall of a syringe.
  • VILA.1.d Another embodiment is a method of making a vessel having a wall having an interior polymer layer enclosed by an exterior polymer layer, one layer made of COC and the other made of polyester.
  • the vessel is made by a process including introducing COC and polyester resin layers into an injection mold through concentric injection nozzles.
  • VILA. l.d. An optional additional step is applying an amorphous carbon coating to the vessel by PECVD, as an inside coating, an outside coating, or as an interlayer coating located between the layers.
  • An optional additional step is applying an SiO x barrier layer to the inside of the vessel wall, where SiO x is defined as before.
  • Another optional additional step is post- treating the SiO x layer with a process gas consisting essentially of oxygen and essentially free of a volatile silicon compound.
  • the SiO x coating can be formed at least partially from a silazane feed gas.
  • VILA. l.d The vessel 80 shown in FIG. 36 can be made from the inside out, for one example, by injection molding the inner wall in a first mold cavity, then removing the core and molded inner wall from the first mold cavity to a second, larger mold cavity, then injection molding the outer wall against the inner wall in the second mold cavity.
  • a tie layer can be provided to the exterior contact surface of the molded inner wall before over-molding the outer wall onto the tie layer.
  • a tie layer can be provided to the interior contact surface of the molded outer wall before over-molding the inner wall onto the tie layer.
  • the vessel 80 shown in FIG. 36 can be made in a two shot mold. This can be done, for one example, by injection molding material for the inner wall from an inner nozzle and the material for the outer wall from a concentric outer nozzle.
  • a tie layer can be provided from a third, concentric nozzle disposed between the inner and outer nozzles. The nozzles can feed the respective wall materials simultaneously.
  • One useful expedient is to begin feeding the outer wall material through the outer nozzle slightly before feeding the inner wall material through the inner nozzle. If there is an intermediate concentric nozzle, the order of flow can begin with the outer nozzle and continue in sequence from the intermediate nozzle and then from the inner nozzle. Or, the order of beginning feeding can start from the inside nozzle and work outward, in reverse order compared to the preceding description.
  • VILA. l.e. Another embodiment is a vessel including a vessel, a barrier coating, and a closure.
  • the vessel is generally tubular and made of thermoplastic material.
  • the vessel has a mouth and a lumen bounded at least in part by a wall having an inner contact surface interfacing with the lumen.
  • a closure covers the mouth and isolates the lumen of the vessel from ambient air.
  • the vessel 80 can also be made, for example of glass of any type used in medical or laboratory applications, such as soda-lime glass, borosilicate glass, or other glass formulations.
  • Other vessels having any shape or size, made of any material, are also possible.
  • One function of coating a glass vessel can be to reduce the ingress of ions in the glass, either intentionally or as impurities, for example sodium, calcium, or others, from the glass to the contents of the vessel, such as a reagent or blood in an evacuated blood collection tube.
  • Another function of coating a glass vessel in whole or in part, such as selectively at contact surfaces contacted in sliding relation to other parts, is to provide lubricity to the coating, for example to ease the insertion or removal of a stopper or passage of a sliding element such as a piston in a syringe.
  • Still another reason to coat a glass vessel is to prevent a reagent or intended sample for the vessel, such as blood, from sticking to the wall of the vessel or an increase in the rate of coagulation of the blood in contact with the wall of the vessel.
  • VILA I.e. i.
  • a related embodiment is a vessel as described in the previous paragraph, in which the barrier coating is made of soda lime glass, borosilicate glass, or another type of glass.
  • FIGS. 23-25 illustrate a vessel 268, which can be an evacuated blood collection tube, having a closure 270 to isolate the lumen 274 from the ambient environment.
  • the closure 270 comprises a interior-facing contact surface 272 exposed to the lumen 274 of the vessel 268 and a wall-contacting contact surface 276 that is in contact with the inner contact surface 278 of the vessel wall 280.
  • the closure 270 is an assembly of a stopper 282 and a shield 284.
  • VILA.2. a. Another embodiment is a method of applying a coating on an elastomeric stopper such as 282.
  • the stopper 282, separate from the vessel 268, is placed in a substantially evacuated chamber.
  • a reaction mixture is provided including plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas. Plasma is formed in the reaction mixture, which is contacted with the stopper.
  • a lubricity and/or hydrophobic layer characterized as defined in the Definition Section, is deposited on at least a portion of the stopper.
  • the wall-contacting contact surface 276 of the closure 270 is coated with a lubricity layer 286.
  • elastomeric compositions of the type useful for fabricating a stopper 282 contain trace amounts of one or more metal ions. These ions sometimes should not be able to migrate into the lumen 274 or come in substantial quantities into contact with the vessel contents, particularly if the sample vessel 268 is to be used to collect a sample for trace metal analysis. It is contemplated for example that coatings containing relatively little organic content, i.e.
  • y and z of Si w O x C y H z as defined in the Definition Section are particularly useful as a metal ion barrier in this application.
  • silica as a metal ion barrier see, for example, Anupama Mallikarjunan, Jasbir Juneja, Guangrong Yang, Shyam P. Murarka, and Toh-Ming Lu, The Effect of Interfacial Chemistry on Metal Ion Penetration into Polymeric Films, Mat. Res. Soc. Symp. Proa, Vol. 734, pp. B9.60.1 to B9.60.6 (Materials Research Society, 2003); U.S. Patents 5578103 and 6200658, and European Appl. EP0697378 A2, which are all incorporated here by reference. It is contemplated, however, that some organic content can be useful to provide a more elastic coating and to adhere the coating to the elastomeric contact surface of the stopper 282.
  • the lubricity and/or hydrophobic layer can be a composite of material having first and second layers, in which the first or inner layer 288 interfaces with the elastomeric stopper 282 and is effective to reduce the transmission of one or more constituents of the stopper 282 into the vessel lumen.
  • the second layer 286 can interface with the inner wall 280 of the vessel and is effective as a lubricity layer to reduce friction between the stopper 282 and the inner wall 280 of the vessel when the stopper 282 is seated on or in the vessel 268.
  • Such composites are described in connection with syringe coatings elsewhere in this specification.
  • the first and second layers 288 and 286 are defined by a coating of graduated properties, in which the values of y and z defined in the Definition Section are greater in the first layer than in the second layer.
  • the lubricity and/or hydrophobic layer can be applied, for example, by PECVD substantially as previously described.
  • the lubricity and/or hydrophobic layer can be, for example, between 0.5 and 5000 nm (5 to 50,000 Angstroms) thick, or between 1 and 5000 nm thick, or between 5 and 5000 nm thick, or between 10 and 5000 nm thick, or between 20 and 5000 nm thick, or between 50 and 5000 nm thick, or between 100 and 5000 nm thick, or between 200 and 5000 nm thick, or between 500 and 5000 nm thick, or between 1000 and 5000 nm thick, or between 2000 and 5000 nm thick, or between 3000 and 5000 nm thick, or between 4000 and 10,000 nm thick.
  • Nanocoatings as applied by PECVD, are contemplated to offer lower resistance to sliding of an adjacent contact surface or flow of an adjacent fluid than micron coatings, as the plasma coating tends to provide a smoother contact surface.
  • VILA.2. a. Still another embodiment is a method of applying a coating of a lubricity and/or hydrophobic layer on an elastomeric stopper.
  • the stopper can be used, for example, to close the vessel previously described.
  • the method includes several parts.
  • a stopper is placed in a substantially evacuated chamber.
  • a reaction mixture is provided comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas. Plasma is formed in the reaction mixture.
  • the stopper is contacted with the reaction mixture, depositing the coating of a lubricity and/or hydrophobic layer on at least a portion of the stopper.
  • the reaction mixture can comprise a hydrocarbon gas, as further described above and below.
  • the reaction mixture can contain oxygen, if lower values of y and z or higher values of x are contemplated.
  • the reaction mixture can be essentially free of an oxidizing gas.
  • the wall-contacting and interior facing contact surfaces 276 and 272 of the stopper 282 are essentially convex, and thus readily treated by a batch process in which a multiplicity of stoppers such as 282 can be located and treated in a single substantially evacuated reaction chamber.
  • the coatings 286 and 288 do not need to present as daunting a barrier to oxygen or water as the barrier coating on the interior contact surface 280 of the vessel 268, as the material of the stopper 282 can serve this function to a large degree.
  • the stopper 282 can be contacted with the plasma.
  • the plasma can be formed upstream of the stopper 282, producing plasma product, and the plasma product can be contacted with the stopper 282.
  • the plasma can be formed by exciting the reaction mixture with electromagnetic energy and/or microwave energy.
  • the plasma forming gas can include an inert gas.
  • the inert gas can be, for example, argon or helium, or other gases described in this disclosure.
  • the organosilicon compound gas can be, or include, HMDSO, OMCTS, any of the other organosilicon compounds mentioned in this disclosure, or a combination of two or more of these.
  • the oxidizing gas can be oxygen or the other gases mentioned in this disclosure, or a combination of two or more of these.
  • the hydrocarbon gas can be, for example, methane, methanol, ethane, ethylene, ethanol, propane, propylene, propanol, acetylene, or a combination of two or more of these.
  • VII.A.2.b Another embodiment is a method of applying a coating of a composition including carbon and one or more elements of Groups III or IV on an elastomeric stopper.
  • a stopper is located in a deposition chamber.
  • VII.A.2.b A reaction mixture is provided in the deposition chamber, including a plasma forming gas with a gaseous source of a Group III element, a Group IV element, or a combination of two or more of these.
  • the reaction mixture optionally contains an oxidizing gas and optionally contains a gaseous compound having one or more C-H bonds.
  • Plasma is formed in the reaction mixture, and the stopper is contacted with the reaction mixture.
  • a coating of a Group III element or compound, a Group IV element or compound, or a combination of two or more of these is deposited on at least a portion of the stopper.
  • FIG. 1 Another embodiment is a vessel including a vessel, a barrier coating, and a closure.
  • the vessel is generally tubular and made of thermoplastic material.
  • the vessel has a mouth and a lumen bounded at least in part by a wall.
  • the wall has an inner contact surface interfacing with the lumen.
  • An at least essentially continuous barrier coating is applied on the inner contact surface of the wall.
  • the barrier coating is effective to provide a substantial shelf life.
  • a closure is provided covering the mouth of the vessel and isolating the lumen of the vessel from ambient air.
  • a vessel 268 such as an evacuated blood collection tube or other vessel is shown.
  • the vessel is, in this embodiment, a generally tubular vessel having an at least essentially continuous barrier coating and a closure.
  • the vessel is made of thermoplastic material having a mouth and a lumen bounded at least in part by a wall having an inner contact surface interfacing with the lumen.
  • the barrier coating is deposited on the inner contact surface of the wall, and is effective to maintain at least 95%, or at least 90%, of the initial vacuum level of the vessel for a shelf life of at least 24 months, optionally at least 30 months, optionally at least 36 months.
  • the closure covers the mouth of the vessel and isolates the lumen of the vessel from ambient air.
  • closure for example the closure 270 illustrated in the Figures or another type of closure, is provided to maintain a partial vacuum and/or to contain a sample and limit or prevent its exposure to oxygen or contaminants.
  • FIGS. 23-25 are based on figures found in U.S. Patent No. 6,602,206, but the present discovery is not limited to that or any other particular type of closure.
  • the closure 270 comprises a interior-facing contact surface 272 exposed to the lumen 274 of the vessel 268 and a wall-contacting contact surface 276 that is in contact with the inner contact surface 278 of the vessel wall 280.
  • the closure 270 is an assembly of a stopper 282 and a shield 284.
  • the stopper 282 defines the wall-contacting contact surface 276 and the inner contact surface 278, while the shield is largely or entirely outside the stoppered vessel 268, retains and provides a grip for the stopper 282, and shields a person removing the closure 270 from being exposed to any contents expelled from the vessel 268, such as due to a pressure difference inside and outside of the vessel 268 when the vessel 268 is opened and air rushes in or out to equalize the pressure difference.
  • the coatings on the vessel wall 280 and the wall contacting contact surface 276 of the stopper can be coordinated.
  • the stopper can be coated with a lubricity silicone layer
  • the vessel wall 280 made for example of PET or glass, can be coated with a harder SiO x layer, or with an underlying SiO x layer and a lubricity overcoat.
  • FIGS 20-22 Another example of a suitable vessel, shown in FIGS 20-22, is a syringe barrel 250 for a medical syringe 252.
  • syringes 252 are sometimes supplied prefilled with saline solution, a pharmaceutical preparation, or the like for use in medical techniques.
  • Pre-filled syringes 252 are also contemplated to benefit from an SiO x barrier or other type of coating on the interior contact surface 254 to keep the contents of the prefilled syringe 252 out of contact with the plastic of the syringe, for example of the syringe barrel 250 during storage.
  • the barrier or other type of coating can be used to avoid leaching components of the plastic into the contents of the barrel through the interior contact surface 254.
  • the front end 260 can optionally be capped and the plunger 258 optionally can be fitted in place before the prefilled syringe 252 is used, closing the barrel 250 at both ends.
  • a cap 262 can be installed either for the purpose of processing the syringe barrel 250 or assembled syringe, or to remain in place during storage of the prefilled syringe 252, up to the time the cap 262 is removed and (optionally) a hypodermic needle or other delivery conduit is fitted on the front end 260 to prepare the syringe 252 for use. VII.B.l. Assemblies
  • FIG. 42 also shows an alternative syringe barrel construction usable, for example, with the embodiments of FIGS. 21, 26, 28, 30, and 34 and adapted for use with the vessel holder 450 of that Figure..
  • FIG. 50 is an exploded view and FIG. 51 is an assembled view of a syringe.
  • the syringe barrel can be processed with the vessel treatment and inspection apparatus of FIGS. 1-22, 26-28, 33-35, 37-39, 44, and 53-54.
  • VII.B.l The installation of a cap 262 makes the barrel 250 a closed-end vessel that can be provided with an SiO x barrier or other type of coating on its interior contact surface 254 in the previously illustrated apparatus, optionally also providing a coating on the interior 264 of the cap and bridging the interface between the cap interior 264 and the barrel front end 260.
  • Suitable apparatus adapted for this use is shown, for example, in FIG. 21, which is analogous to FIG. 2 except for the substitution of the capped syringe barrel 250 for the vessel 80 of FIG. 2.
  • FIG. 52 is a view similar to FIG. 42, but showing a syringe barrel being treated that has no flange or finger stops 440.
  • the syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-51, and 53-54.
  • Still another embodiment is a vessel having a lubricity layer
  • VII.B. l.a The precursor is applied to a substrate under conditions effective to form a coating.
  • the coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • the applying step is carried out by vaporizing the precursor and providing it in the vicinity of the substrate.
  • any of the Embodiments VII.A. l.a.i optionally a plasma, optionally a non-hollow-cathode plasma, is formed in the vicinity of the substrate.
  • the precursor is provided in the substantial absence of oxygen.
  • the precursor is provided in the substantial absence of a carrier gas.
  • the precursor is provided in the substantial absence of nitrogen.
  • the precursor is provided at less than 1 Torr absolute pressure.
  • the precursor is provided to the vicinity of a plasma emission.
  • the precursor its reaction product is applied to the substrate at a thickness of 1 to 5000 nm thick, or 10 to 1000 nm thick, or 10-200 nm thick, or 20 to 100 nm thick.
  • the substrate comprises glass.
  • the substrate comprises a polymer, optionally a polycarbonate polymer, optionally an olefin polymer, optionally a cyclic olefin copolymer, optionally a polypropylene polymer, optionally a polyester polymer, optionally a polyethylene terephthalate polymer.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes powered, for example, at a RF frequency as defined above, for example a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • a RF frequency as defined above, for example a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W.
  • the ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml.
  • power levels are suitable for applying lubricity layers to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
  • VH.B.l.a Another embodiment is a lubricity layer, characterized as defined in the Definition Section, on the inner wall of a syringe barrel.
  • the coating is produced from a PECVD process using the following materials and conditions.
  • a cyclic precursor is optionally employed, selected from a monocyclic siloxane, a polycyclic siloxane, or a combination of two or more of these, as defined elsewhere in this specification for lubricity layers.
  • a suitable cyclic precursor comprises octamethylcyclotetrasiloxane (OMCTS), optionally mixed with other precursor materials in any proportion.
  • the cyclic precursor consists essentially of octamethycyclotetrasiloxane (OMCTS), meaning that other precursors can be present in amounts which do not change the basic and novel properties of the resulting lubricity layer, i.e. its reduction of the plunger sliding force or breakout force of the coated contact surface.
  • OCTS octamethycyclotetrasiloxane
  • VH.B.l.a At least essentially no oxygen, as defined in the Definition Section, is added to the process.
  • VII.B.1. Another embodiment is a vessel having a hydrophobic layer, characterized as defined in the Definition Section, on the inside wall.
  • the coating is made as explained for the lubricant coating of similar composition, but under conditions effective to form a hydrophobic contact surface having a higher contact angle than the untreated substrate.
  • the substrate comprises glass or a polymer.
  • the glass optionally is borosilicate glass.
  • the polymer is optionally a polycarbonate polymer, optionally an olefin polymer, optionally a cyclic olefin copolymer, optionally a polypropylene polymer, optionally a polyester polymer, optionally a polyethylene terephthalate polymer.
  • a syringe including a plunger, a syringe barrel, and a lubricity layer, characterized as defined in the Definition Section.
  • the syringe barrel includes an interior contact surface receiving the plunger for sliding.
  • the lubricity layer is disposed on the interior contact surface of the syringe barrel.
  • the lubricity layer is less than 1000 nm thick and effective to reduce the breakout force or the plunger sliding force necessary to move the plunger within the barrel. Reducing the plunger sliding force is alternatively expressed as reducing the coefficient of sliding friction of the plunger within the barrel or reducing the plunger force; these terms are regarded as having the same meaning in this specification.
  • the syringe 544 of FIGS. 50-51 comprises a plunger 546 and a syringe barrel 548.
  • the syringe barrel 548 has an interior contact surface 552 receiving the plunger for sliding 546.
  • the interior contact surface 552 of the syringe barrel 548 further comprises a lubricity layer 554, characterized as defined in the Definition Section.
  • the lubricity layer is less than 1000 nm thick, optionally less than 500 nm thick, optionally less than 200 nm thick, optionally less than 100 nm thick, optionally less than 50 nm thick, and is effective to reduce the breakout force necessary to overcome adhesion of the plunger after storage or the plunger sliding force necessary to move the plunger within the barrel after it has broken away.
  • the lubricity layer is characterized by having a plunger sliding force or breakout force lower than that of the uncoated contact surface.
  • VH.B.l.a Any of the above precursors of any type can be used alone or in combinations of two or more of them to provide a lubricity layer.
  • VH.B.l.a In addition to utilizing vacuum processes, low temperature atmospheric (non-vacuum) plasma processes can also be utilized to induce molecular ionization and deposition through precursor monomer vapor delivery optionally in a non-oxidizing atmosphere such as helium or argon. Separately, thermal CVD can be considered via flash thermolysis deposition.
  • VH.B.l.a The approaches above are similar to vacuum PECVD in that the contact surface coating and crosslinking mechanisms can occur simultaneously.
  • VH.B.l.a Yet another expedient contemplated for any coating or coatings described here is a coating that is not uniformly applied over the entire interior 88 of a vessel. For example, a different or additional coating can be applied selectively to the cylindrical portion of the vessel interior, compared to the hemispherical portion of the vessel interior at its closed end 84, or vice versa. This expedient is particularly contemplated for a syringe barrel or a sample collection tube as described below, in which a lubricity layer might be provided on part or all of the cylindrical portion of the barrel, where the plunger or piston or closure slides, and not elsewhere. [00301] VH.B.l.a.
  • the precursor can be provided in the presence, substantial absence, or absence of oxygen, in the presence, substantial absence, or absence of nitrogen, or in the presence, substantial absence, or absence of a carrier gas.
  • the precursor alone is delivered to the substrate and subjected to PECVD to apply and cure the coating.
  • the precursor can be provided at less than 1 Torr absolute pressure.
  • the precursor can be provided to the vicinity of a plasma emission.
  • the precursor its reaction product can be applied to the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm., or 10-200 nm, or 20 to 100 nm.
  • the substrate can comprise glass, or a polymer, for example one or more of a polycarbonate polymer, an olefin polymer (for example a cyclic olefin copolymer or a polypropylene polymer), or a polyester polymer (for example, a polyethylene terephthalate polymer).
  • a polymer for example one or more of a polycarbonate polymer, an olefin polymer (for example a cyclic olefin copolymer or a polypropylene polymer), or a polyester polymer (for example, a polyethylene terephthalate polymer).
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes powered at a RF frequency as defined in this description.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with sufficient electric power to generate a lubricity layer.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W.
  • the ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml.
  • These power levels are suitable for applying lubricity layers to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
  • the coating can be cured, as by polymerizing or crosslinking the coating, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate. Curing can occur during the application process such as PECVD, or can be carried out or at least completed by separate processing.
  • VH.B.l.a Although plasma deposition has been used herein to demonstrate the coating characteristics, alternate deposition methods can be used as long as the chemical composition of the starting material is preserved as much as possible while still depositing a solid film that is adhered to the base substrate.
  • the coating material can be applied onto the syringe barrel (from the liquid state) by spraying the coating or dipping the substrate into the coating, where the coating is either the neat precursor a solvent-diluted precursor (allowing the mechanical deposition of a thinner coating).
  • the coating optionally can be crosslinked using thermal energy, UV energy, electron beam energy, plasma energy, or any combination of these.
  • VH.B.l.a Application of a silicone precursor as described above onto a contact surface followed by a separate curing step is also contemplated.
  • the conditions of application and curing can be analogous to those used for the atmospheric plasma curing of pre-coated polyfluoroalkyl ethers, a process practiced under the trademark TriboGlide®. More details of this process can be found at http://www.triboglide.com/process.htm.
  • the area of the part to be coated can optionally be pre- treated with an atmospheric plasma. This pretreatment cleans and activates the contact surface so that it is receptive to the lubricant that is sprayed in the next step.
  • VII.B.l.a The lubrication fluid, in this case one of the above precursors or a polymerized precursor, is then sprayed on to the contact surface to be treated.
  • IVEK precision dispensing technology can be used to accurately atomize the fluid and create a uniform coating.
  • VH.B.l.a The coating is then bonded or crosslinked to the part, again using an atmospheric plasma field. This both immobilizes the coating and improves the lubricant's performance.
  • the atmospheric plasma can be generated from ambient air in the vessel, in which case no gas feed and no vacuum drawing equipment is needed.
  • the vessel is at least substantially closed while plasma is generated, to minimize the power requirement and prevent contact of the plasma with contact surfaces or materials outside the vessel.
  • Lubricity layer SiO x Barrier, Lubricity Layer, Contact surface Treatment Contact surface treatment
  • VH.B.l.a.i. Another embodiment is a syringe comprising a barrel defining a lumen and having an interior contact surface slidably receiving a plunger, i.e. receiving a plunger for sliding contact to the interior contact surface.
  • VH.B.l.a.i The syringe barrel is made of thermoplastic base material.
  • VH.B.l.a.i the interior contact surface of the barrel is coated with an SiO x barrier layer as described elsewhere in this specification.
  • VH.B.l.a.i A lubricity layer is applied to the barrel interior contact surface, the plunger, or both, or to the previously applied SiO x barrier layer.
  • the lubricity layer can be provided, applied, and cured as set out in embodiment VH.B.l.a or elsewhere in this
  • the lubricity layer can be applied, in any embodiment, by PECVD.
  • the lubricity layer is deposited from an organosilicon precursor, and is less than 1000 nm thick.
  • a contact surface treatment is carried out on the lubricity layer in an amount effective to reduce the leaching or extractables of the lubricity layer, the thermoplastic base material, or both.
  • the treated contact surface can thus act as a solute retainer.
  • This contact surface treatment can result in a skin coating, e.g.
  • a skin coating which is at least 1 nm thick and less than 100 nm thick, or less than 50 nm thick, or less than 40 nm thick, or less than 30 nm thick, or less than 20 nm thick, or less than 10 nm thick, or less than 5 nm thick, or less than 3 nm thick, or less than 2 nm thick, or less than 1 nm thick, or less than 0.5 nm thick.
  • leaching refers to material transferred out of a substrate, such as a vessel wall, into the contents of a vessel, for example a syringe. Commonly, leachables are measured by storing the vessel filled with intended contents, then analyzing the contents to determine what material leached from the vessel wall into the intended contents. “Extraction” refers to material removed from a substrate by introducing a solvent or dispersion medium other than the intended contents of the vessel, to determine what material can be removed from the substrate into the extraction medium under the conditions of the test.
  • the contact surface treatment resulting in a solute retainer optionally can be a SiO x layer as previously defined in this specification or a hydrophobic layer, characterized as defined in the Definition Section.
  • the contact surface treatment can be applied by PECVD deposit of SiO x or a hydrophobic layer.
  • the contact surface treatment can be applied using higher power or stronger oxidation conditions than used for creating the lubricity layer, or both, thus providing a harder, thinner, continuous solute retainer 539.
  • Contact surface treatment can be less than 100 nm deep, optionally less than 50 nm deep, optionally less than 40 nm deep, optionally less than 30 nm deep, optionally less than 20 nm deep, optionally less than 10 nm deep, optionally less than 5 nm deep, optionally less than 3 nm deep, optionally less than 1 nm deep, optionally less than 0.5 nm deep, optionally between 0.1 and 50 nm deep in the lubricity layer.
  • the solute retainer is contemplated to provide low solute leaching performance to the underlying lubricity and other layers, including the substrate, as required.
  • This retainer would only need to be a solute retainer to large solute molecules and oligomers (for example siloxane monomers such as HMDSO, OMCTS, their fragments and mobile oligomers derived from lubricants, for example a "leachables retainer") and not a gas (Oi/Ni/CC water vapor) barrier layer.
  • a solute retainer can, however, also be a gas barrier (e.g. the SiOx coating according to present invention.
  • the "leachables barrier” will be sufficiently thin that, upon syringe plunger movement, the plunger will readily penetrate the "solute retainer” exposing the sliding plunger nipple to the lubricity layer immediately below to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • the contact surface treatment can be performed by oxidizing the contact surface of a previously applied lubricity layer, as by exposing the contact surface to oxygen in a plasma environment.
  • the plasma environment described in this specification for forming SiO x coatings can be used.
  • atmospheric plasma conditions can be employed in an oxygen-rich environment.
  • the lubricity layer and solute retainer optionally can be cured at the same time.
  • the lubricity layer can be at least partially cured, optionally fully cured, after which the contact surface treatment can be provided, applied, and the solute retainer can be cured.
  • the lubricity layer and solute retainer are composed, and present in relative amounts, effective to provide a breakout force, plunger sliding force, or both that is less than the corresponding force required in the absence of the lubricity layer and contact surface treatment.
  • the thickness and composition of the solute retainer are such as to reduce the leaching of material from the lubricity layer into the contents of the syringe, while allowing the underlying lubricity layer to lubricate the plunger. It is contemplated that the solute retainer will break away easily and be thin enough that the lubricity layer will still function to lubricate the plunger when it is moved.
  • the lubricity and contact surface treatments can be applied on the barrel interior contact surface. In another contemplated embodiment, the lubricity and contact surface treatments can be applied on the plunger. In still another contemplated embodiment, the lubricity and contact surface treatments can be applied both on the barrel interior contact surface and on the plunger. In any of these embodiments, the optional SiO x barrier layer on the interior of the syringe barrel can either be present or absent.
  • VH.B.l.a.i One embodiment contemplated is a plural-layer, e.g. a 3-layer, configuration applied to the inside contact surface of a syringe barrel.
  • Layer 1 can be an SiO x gas barrier made by PECVD of HMDSO, OMCTS, or both, in an oxidizing atmosphere. Such an atmosphere can be provided, for example, by feeding HMDSO and oxygen gas to a PECVD coating apparatus as described in this specification.
  • Layer 2 can be a lubricity layer using OMCTS applied in a non-oxidizing atmosphere. Such a non-oxidizing atmosphere can be provided, for example, by feeding OMCTS to a PECVD coating apparatus as described in this specification, optionally in the substantial or complete absence of oxygen.
  • a subsequent solute retainer can be formed by a treatment forming a thin skin layer of SiO x or a hydrophobic layer as a solute retainer using higher power and oxygen using OMCTS and/or HMDSO.
  • VH.B.l.a.i Certain of these plural-layer coatings are contemplated to have one or more of the following optional advantages, at least to some degree. They can address the reported difficulty of handling silicone, since the solute retainer can confine the interior silicone and prevent if from migrating into the contents of the syringe or elsewhere, resulting in fewer silicone particles in the deliverable contents of the syringe and less opportunity for interaction between the lubricity layer and the contents of the syringe. They can also address the issue of migration of the lubricity layer away from the point of lubrication, improving the lubricity of the interface between the syringe barrel and the plunger. For example, the break-free force can be reduced and the drag on the moving plunger can be reduced, or optionally both.
  • VH.B.l.a.i It is contemplated that when the solute retainer is broken, the solute retainer will continue to adhere to the lubricity layer and the syringe barrel, which can inhibit any particles from being entrained in the deliverable contents of the syringe.
  • VH.B.l.a.i Certain of these coatings will also provide manufacturing advantages, particularly if the barrier coating, lubricity layer and contact surface treatment are applied in the same apparatus, for example the illustrated PECVD apparatus.
  • the SiO x barrier coating, lubricity layer, and contact surface treatment can all be applied in one PECVD apparatus, thus greatly reducing the amount of handling necessary.
  • barrier coating can be formed using the same precursors and varying the process.
  • an SiO x gas barrier layer can be applied using an OMCTS precursor under high power/high 0 2 conditions, followed by applying a lubricity layer applied using an OMCTS precursor under low power and/or in the substantial or complete absence of oxygen, finishing with a contact surface treatment using an OMCTS precursor under intermediate power and oxygen.
  • VII.B.l.b Syringe having barrel with SiO x coated interior and barrier coated exterior
  • a syringe 544 including a plunger 546, a barrel 548, and interior and exterior barrier coatings 554 and 602.
  • the barrel 548 can be made of thermoplastic base material defining a lumen 604.
  • the barrel 548 can have an interior contact surface 552 receiving the plunger for sliding 546 and an exterior contact surface 606.
  • a barrier coating 554 of SiO x in which x is from about 1.5 to about 2.9, can be provided on the interior contact surface 552 of the barrel 548.
  • a barrier coating 602 of a resin can be provided on the exterior contact surface 606 of the barrel 548.
  • the thermoplastic base material optionally can include a polyolefin, for example polypropylene or a cyclic olefin copolymer (for example the material sold under the trademark TOPAS®), a polyester, for example polyethylene terephthalate, a polycarbonate, for example a bisphenol A polycarbonate thermoplastic, or other materials.
  • a polyolefin for example polypropylene or a cyclic olefin copolymer (for example the material sold under the trademark TOPAS®)
  • a polyester for example polyethylene terephthalate
  • a polycarbonate for example a bisphenol A polycarbonate thermoplastic, or other materials.
  • Composite syringe barrels are contemplated having any one of these materials as an outer layer and the same or a different one of these materials as an inner layer. Any of the material combinations of the composite syringe barrels or sample tubes described elsewhere in this specification can also be used.
  • the resin optionally can include polyvinylidene chloride in homopolymer or copolymer form.
  • the PVdC homopolymers (trivial name: Saran) or copolymers described in US Patent 6,165,566, incorporated here by reference, can be employed.
  • the resin optionally can be applied onto the exterior contact surface of the barrel in the form of a latex or other dispersion.
  • the syringe barrel 548 optionally can include a lubricity layer disposed between the plunger and the barrier coating of SiO x . Suitable lubricity layers are described elsewhere in this specification.
  • the lubricity layer optionally can be applied by PECVD and optionally can include material characterized as defined in the Definition Section.
  • the syringe barrel 548 optionally can include a contact surface treatment covering the lubricity layer in an amount effective to reduce the leaching of the lubricity layer, constituents of the thermoplastic base material, or both into the lumen 604.
  • VII.B.l.c Even another embodiment is a method of making a syringe as described in any of the embodiments of part VII.B. l.b, including a plunger, a barrel, and interior and exterior barrier coatings.
  • a barrel is provided having an interior contact surface for receiving the plunger for sliding and an exterior contact surface.
  • a barrier coating of SiO x is provided on the interior contact surface of the barrel by PECVD.
  • a barrier coating of a resin is provided on the exterior contact surface of the barrel.
  • the plunger and barrel are assembled to provide a syringe.
  • the resin optionally can be applied via dip coating of the latex onto the exterior contact surface of the barrel, spray coating of the latex onto the exterior contact surface of the barrel, or both, providing plastic-based articles offering improved gas and vapor barrier performance.
  • Polyvinylidene chloride plastic laminate articles can be made that provide significantly improved gas barrier performance versus the non-laminated plastic article.
  • the resin optionally can be heat cured.
  • the resin optionally can be cured by removing water. Water can be removed by heat curing the resin, exposing the resin to a partial vacuum or low-humidity environment, catalytically curing the resin, or other expedients.
  • VII.B.l.c An effective thermal cure schedule is contemplated to provide final drying to permit PVdC crystallization, offering barrier performance.
  • Primary curing can be carried out at an elevated temperature, for example between 180-310°F (82-154°C), of course depending on the heat tolerance of the thermoplastic base material.
  • Barrier performance after the primary cure optionally can be about 85% of the ultimate barrier performance achieved after a final cure.
  • a final cure can be carried out at temperatures ranging from ambient temperature, such as about 65-75°F (18-24°C) for a long time (such as 2 weeks) to an elevated temperature, such as 122°F (50°C), for a short time, such as four hours.
  • PVdC -plastic laminate articles in addition to superior barrier performance, are optionally contemplated to provide one or more desirable properties such as colorless transparency, good gloss, abrasion resistance, printability, and mechanical strain resistance.
  • a plunger for a syringe including a piston and a push rod.
  • the piston has a front face, a generally cylindrical side face, and a back portion, the side face being configured to movably seat within a syringe barrel.
  • the front face has a barrier coating.
  • the push rod engages the back portion and is configured for advancing the piston in a syringe barrel.
  • a plunger for a syringe including a piston, a lubricity layer, and a push rod.
  • the piston has a front face, a generally cylindrical side face, and a back portion.
  • the side face is configured to movably seat within a syringe barrel.
  • the lubricity layer interfaces with the side face.
  • the push rod engages the back portion of the piston and is configured for advancing the piston in a syringe barrel.
  • a syringe including a plunger, a syringe barrel, and a Luer fitting.
  • the syringe includes a barrel having an interior contact surface receiving the plunger for sliding.
  • the Luer fitting includes a Luer taper having an internal passage defined by an internal contact surface.
  • the Luer fitting is formed as a separate piece from the syringe barrel and joined to the syringe barrel by a coupling.
  • the internal passage of the Luer taper has a barrier coating of SiO x .
  • the syringe 544 optionally can include a Luer fitting 556 comprising a Luer taper 558 to receive a cannula mounted on a complementary Luer taper (not shown, conventional).
  • the Luer taper 558 has an internal passage 560 defined by an internal contact surface 562.
  • the Luer fitting 556 optionally is formed as a separate piece from the syringe barrel 548 and joined to the syringe barrel 548 by a coupling 564.
  • the coupling 564 in this instance has a male part 566 and a female part 568 that snap together to secure the Luer fitting in at least substantially leak proof fashion to the barrel 548.
  • the internal contact surface 562 of the Luer taper can include a barrier coating 570 of SiO x .
  • the barrier coating can be less than 100 nm thick and effective to reduce the ingress of oxygen into the internal passage of the Luer fitting.
  • the barrier coating can be applied before the Luer fitting is joined to the syringe barrel.
  • the syringe of FIGS. 50-51 also has an optional locking collar 572 that is internally threaded so to lock the complementary Luer taper of a cannula in place on the taper 558.
  • Still another embodiment is a lubricity layer.
  • This coating can be of the type made by the following process.
  • any of the precursors mentioned elsewhere in this specification can be used, alone or in combination.
  • the precursor is applied to a substrate under conditions effective to form a coating.
  • the coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • VII.B.4. a. Another embodiment is a method of applying a lubricity layer.
  • An organosilicon precursor is applied to a substrate under conditions effective to form a coating.
  • the coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • Even another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising an organometallic precursor, optionally an organosilicon precursor, optionally a linear siloxane, a linear silazane, a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has a density between 1.25 and 1.65 g/cm optionally between 1.35 and 1.55 g/cm 3 , optionally between 1.4 and 1.5 g/cm 3 , optionally between 1.44 and 1.48 g/cm 3 as determined by X-ray reflectivity (XRR).
  • XRR X-ray reflectivity
  • Still another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising an organometallic precursor, optionally an organosilicon precursor, optionally a linear siloxane, a linear silazane, a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has as an outgas component one or more oligomers containing repeating - (Me) 2 SiO- moieties, as determined by gas chromatography / mass spectrometry.
  • the coating meets the limitations of any of embodiments VII.B.4.a or VII.B.4.b.A.585h.
  • the coating outgas component as determined by gas chromatography / mass spectrometry is substantially free of trimethylsilanol.
  • the coating outgas component can be at least 10 ng/test of oligomers containing repeating -(Me) 2 SiO- moieties, as determined by gas chromatography / mass spectrometry using the following test conditions:
  • MSD Mass Selective Detector
  • the outgas component can include at least 20 ng/test of oligomers containing repeating -(Me) 2 SiO- moieties.
  • the feed gas comprises a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these, for example a monocyclic siloxane, a monocyclic silazane, or any combination of two or more of these, for example octamethylcyclotetrasiloxane.
  • the lubricity layer of any embodiment can have a thickness measured by transmission electron microscopy (TEM) between 1 and 500 nm, optionally between 10 and 500 nm, optionally between 20 and 200 nm, optionally between 20 and 100 nm, optionally between 30 and 100 nm.
  • TEM transmission electron microscopy
  • VII.BAb Another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has an atomic concentration of carbon, normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), greater than the atomic concentration of carbon in the atomic formula for the feed gas.
  • XPS X-ray photoelectron spectroscopy
  • the coating meets the limitations of embodiments VII.BAa or VII.BAb.A.
  • the atomic concentration of carbon increases by from 1 to 80 atomic percent (as calculated and based on the XPS conditions in Example 15), alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 50 atomic percent, alternatively from 35 to 45 atomic percent, alternatively from 37 to 41 atomic percent.
  • VTI.BAb An additional aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has an atomic concentration of silicon, normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), less than the atomic concentration of silicon in the atomic formula for the feed gas.
  • XPS X-ray photoelectron spectroscopy
  • the coating meets the limitations of embodiments VII.BAa or VII.BAb.A.
  • VII.BAb Optionally, the atomic concentration of silicon decreases by from 1 to 80 atomic percent (as calculated and based on the XPS conditions in Example 15), alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 55 atomic percent, alternatively from 40 to 50 atomic percent, alternatively from 42 to 46 atomic percent.
  • VII.BAb Lubricity layers having combinations of any two or more properties recited in Section VII.B.4 are also expressly contemplated.
  • a coated vessel or container as described herein and/or prepared according to a method described herein can be used for reception and/or storage and/or delivery of a compound or composition.
  • the compound or composition can be sensitive, for example air- sensitive, oxygen-sensitive, sensitive to humidity and/or sensitive to mechanical influences. It can be a biologically active compound or composition, for example a medicament like insulin or a composition comprising insulin. In another aspect, it can be a biological fluid, optionally a bodily fluid, for example blood or a blood fraction.
  • the compound or composition is a product to be administrated to a subject in need thereof, for example a product to be injected, like blood (as in transfusion of blood from a donor to a recipient or reintroduction of blood from a patient back to the patient) or insulin.
  • a product to be injected like blood (as in transfusion of blood from a donor to a recipient or reintroduction of blood from a patient back to the patient) or insulin.
  • a coated vessel or container as described herein and/or prepared according to a method described herein can further be used for protecting a compound or composition contained in its interior space against mechanical and/or chemical effects of the contact surface of the uncoated vessel material. For example, it can be used for preventing or reducing precipitation and/or clotting or platelet activation of the compound or a component of the composition, for example insulin precipitation or blood clotting or platelet activation.
  • VII.C It can further be used for protecting a compound or composition contained in its interior against the environment outside of the vessel, for example by preventing or reducing the entry of one or more compounds from the environment surrounding the vessel into the interior space of the vessel.
  • Such environmental compound can be a gas or liquid, for example an atmospheric gas or liquid containing oxygen, air, and/or water vapor.
  • a coated vessel as described herein can also be evacuated and stored in an evacuated state.
  • the coating allows better maintenance of the vacuum in comparison to a corresponding uncoated vessel.
  • the coated vessel is a blood collection tube.
  • the tube can also contain an agent for preventing blood clotting or platelet activation, for example EDTA or heparin.
  • any of the above-described embodiments can be made, for example, by providing as the vessel a length of tubing from about 1 cm to about 200 cm, optionally from about 1 cm to about 150 cm, optionally from about 1 cm to about 120 cm, optionally from about 1 cm to about 100 cm, optionally from about 1 cm to about 80 cm, optionally from about 1 cm to about 60 cm, optionally from about 1 cm to about 40 cm, optionally from about 1 cm to about 30 cm long, and processing it with a probe electrode as described below.
  • relative motion between the probe and the vessel can be useful during coating formation. This can be done, for example, by moving the vessel with respect to the probe or moving the probe with respect to the vessel.
  • the coating can be thinner or less complete than can be preferred for a barrier coating, as the vessel in some embodiments will not require the high barrier integrity of an evacuated blood collection tube.
  • the vessel has a central axis.
  • the vessel wall is sufficiently flexible to be flexed at least once at 20 °C, without breaking the wall, over a range from at least substantially straight to a bending radius at the central axis of not more than 100 times as great as the outer diameter of the vessel.
  • the bending radius at the central axis is not more than 90 times as great as, or not more than 80 times as great as, or not more than 70 times as great as, or not more than 60 times as great as, or not more than 50 times as great as, or not more than 40 times as great as, or not more than 30 times as great as, or not more than 20 times as great as, or not more than 10 times as great as, or not more than 9 times as great as, or not more than 8 times as great as, or not more than 7 times as great as, or not more than 6 times as great as, or not more than 5 times as great as, or not more than 4 times as great as, or not more than 3 times as great as, or not more than 2 times as great as, or not more than, the outer diameter of the vessel.
  • the vessel wall can be a fluid-contacting contact surface made of flexible material.
  • the vessel lumen can be the fluid flow passage of a pump.
  • the vessel can be a blood bag adapted to maintain blood in good condition for medical use.
  • the polymeric material can be a silicone elastomer or a thermoplastic polyurethane, as two examples, or any material suitable for contact with blood, or with insulin.
  • the vessel has an inner diameter of at least 2 mm, or at least 4 mm.
  • the vessel is a tube.
  • the lumen has at least two open ends.
  • Even another embodiment is a blood containing vessel.
  • a blood transfusion bag a blood sample collection vessel in which a sample has been collected
  • the tubing of a heart-lung machine a flexible-walled blood collection bag, or tubing used to collect a patient' s blood during surgery and reintroduce the blood into the patient's vasculature.
  • a particularly suitable pump is a centrifugal pump or a peristaltic pump.
  • the vessel has a wall; the wall has an inner contact surface defining a lumen.
  • the inner contact surface of the wall has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section.
  • the coating can be as thin as monomolecular thickness or as thick as about 1000 nm.
  • the vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
  • An embodiment is a blood containing vessel including a wall and having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer.
  • the coating can also comprise or consist essentially of SiO x , where x is as defined in this specification.
  • the thickness of the coating is within the range from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • the vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
  • VII.C.2. Another embodiment is a vessel having a wall.
  • the wall has an inner contact surface defining a lumen and has an at least partial coating of a hydrophobic layer, where optionally w, x, y, and z are as previously defined in the Definition Section.
  • the thickness of the coating is from monomolecular thickness to about 1000 nm thick on the inner contact surface. The coating is effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface, compared to the same type of wall uncoated with a hydrophobic layer.
  • VII.C.2. Another embodiment is a vessel including a wall and having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer, the thickness of the coating being from monomolecular thickness to about 1000 nm thick on the inner contact surface, the coating being effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface.
  • Another embodiment is a blood containing vessel having a wall having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a composition comprising one or more elements of Group III, one or more elements of Group IV , or a combination of two or more of these.
  • the thickness of the coating is between monomolecular thickness and about 1000 nm thick, inclusive, on the inner contact surface.
  • the vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
  • the coating of the Group III or IV Element is effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface of the vessel wall.
  • a coated vessel or container as described herein can be used for preventing or reducing the escape of a compound or composition contained in the vessel into the environment surrounding the vessel.
  • Another embodiment is an insulin containing vessel including a wall having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section.
  • the coating can be from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • Insulin is disposed within the lumen in contact with the Si w O x C y H z coating.
  • Still another embodiment is an insulin containing vessel including a wall and having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section, the thickness of the coating being from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • Insulin for example pharmaceutical insulin FDA approved for human use, is disposed within the lumen in contact with the hydrophobic layer.
  • hydrophobic layer characterized as defined in the Definition Section, will reduce the adhesion or precipitation forming tendency of the insulin in a delivery tube of an insulin pump, as compared to its properties in contact with an unmodified polymeric contact surface. This property is
  • the coating of a hydrophobic layer is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface, compared to the same contact surface absent the hydrophobic layer.
  • Even another embodiment is a vessel again comprising a wall and having an inner contact surface defining a lumen.
  • the inner contact surface includes an at least partial coating of a hydrophobic layer.
  • the thickness of the coating is in the range from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • the coating is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface.
  • FIG. 1 Another embodiment is an insulin containing vessel including a wall having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a composition comprising carbon, one or more elements of Group III, one or more elements of Group IV, or a combination of two or more of these.
  • the coating can be from monomolecular thickness to about 1000 nm thick on the inner contact surface. Insulin is disposed within the lumen in contact with the coating.
  • the coating of a composition comprising carbon, one or more elements of Group III, one or more elements of Group IV, or a combination of two or more of these is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface, compared to the same contact surface absent the coating.
  • a second antimicrobially effective treatment is applied to the contact surface with its first treatment.
  • the second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
  • antimicrobial agent is silver or a silver compound.
  • Suitable antimicrobial treatments include the following.
  • a silver ion coating is applied by dip or paint to inhibit infections in invasive medical devices and to create burn and wound treatments.
  • the device must be properly prepared first through sterilization and removal of debris before any coating process is performed.
  • This traditional coating method has worked well, and several companies have proprietary application methods using nano-sized silver crystals for wound treatments.
  • Devices and wound dressings treated with silver must be able to withstand the high heat associated with coating technologies. For example, certain coating technologies, such as plating, could not be used to apply silver oxide to a gauze bandage or disposable diaper-the fabric would disintegrate.
  • silver is used in conjunction with certain surfaces or coatings.
  • many medical devices such as catheters, are manufactured with a hydrophobic polymer matrix, which limits the silver ion concentration near the device surface.
  • Silver oxide requires the presence of moisture to release its anti-microbial properties. Affixing silver oxide to a hydrophobic polymer reduces the moisture present and thus decreases silver's antimicrobial effect.
  • Commercially available devices coated with these processes may experience limited effectiveness.
  • silver-antimicrobial compounds address this problem by adding silver mixed with a ceramic, such as zirconium phosphate, directly into the polymer material before it is manufactured into a medical device.
  • a ceramic such as zirconium phosphate
  • incorporation of the antimicrobial material into the polymer from which the contact surface is made is regarded as an antimicrobial treatment of the surface.
  • iontophoric polymers are designed to release silver ions when wet with body fluids.
  • an electrolytic fluid such as saline, blood, drug preparations, or urine
  • the metal powders become a mass of tiny electrodes.
  • Each molecule becomes an anode or a cathode, making the polymer conductive, which causes it to release the silver ions.
  • the ion exchange is a slow process, which is a benefit because it may extend the antimicrobial effect.8
  • This application technique has been used in catheters. Other uses being explored include orthopedic implants, pacemaker leads, suture leads, and feeding tubes.
  • the newest innovation for silver oxide antimicrobials involves surface-engineered ordered nanostructures of silver oxide that are built on the medical device surface.
  • the approach employs nanotechnology to apply antimicrobial silver to medical devices.
  • Nanotechnology may provide the most effective platform to maximize the antimicrobial capability of silver.
  • the nanostructures comprise silver particles. Because each tiny particle in a nanostmcture has its own surface area, it increases the overall surface area of the silver oxide. A larger surface area means more silver can interact with body fluids to encounter and inhibit microbes. Surface engineering of ordered nanostructures takes place on the nanometer scale.
  • IPD ionic plasma deposition
  • Depositing material ions are accelerated to ensure that the depositing species are the correct energy for the desired process and for the medical device polymer material. This allows for a broad range of custom stoichiometries and demonstrates that IPD technology is adaptable when used to treat medical polymers.
  • Low-temperature polymers are used in soft-tissue implants. These polymers, such as polyethylene, polyester, polypropylene, and even Teflon (PTFE), can be treated with IPD nanotechnology.
  • IPD can be controlled for particle size, density, and rate of deposition. Because it incorporates a high degree of control and low heat application, IPD also has traits of adhesion and repeatability for silver application. The structures are laid down in a highly ordered surface. Deposition is possible in concentric plasma to almost any length. Source-material use is very efficient, so that high- volume precious-metal applications such as silver, platinum, and gold are economical.
  • Silver oxide application should maintain conformal quality of the medical device surface regardless of surface morphology.
  • the silver is deposited into blind holes, vias, and cavities with aspect ratios of 5: 1. Coatings are now measured in angstroms, and application layers must be extremely thin.9 IPD surface-engineered
  • nanotechnology has ultra-thin-film capability, which can be used to treat flexible, porous materials such as antimicrobial bandages.
  • silver ions can be incorporated in carrier particles - like zeolites - which can then be applied to the contact surface, preferably after it is treated by PECVD to provide a functional coating.
  • nanoparticles or ions of silver can be entrained in an airstream, conveyed into plasma enhanced chemical vapor deposition or similar apparatus, and driven into the contact surface or a surface coating on the contact surface, as by applying a DC bias to an electrode behind the contact surface relative to the source of nanoparticles.
  • the invention is believed to function as follows, although this theory of operation does not limit the invention, and any inaccuracy of this theory does not change the scope of the invention.
  • Silver ions are believed to work at the surface of a product through the controlled release of silver ions which attack microbes and inhibit their growth.
  • the silver ions exchange with other positive ions (often sodium) from the moisture in the environment, effecting a release of silver "on demand".
  • Silver ions are randomly oriented and distributed through the surface of a fiber, polymer or coating. In conditions that support bacterial growth, positive ions, in ambient moisture, exchange with silver ions. The exchanged silver ions are now available to control microbial growth. Silver ions attack multiple targets in the microbe to prevent it from growing to a destructive population. They are believed to fight cell growth in three ways:
  • Example 0 Basic Protocols for Forming and Coating Tubes and Syringe Barrels
  • Protocol for Forming COC Tube (used, e.g., in Examples 1, 19)
  • Cyclic olefin copolymer (COC) tubes of the shape and size commonly used as evacuated blood collection tubes (“COC tubes”) were injection molded from Topas® 8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG, Frankfurt am Main, Germany, having these dimensions: 75 mm length, 13 mm outer diameter, and 0.85 mm wall thickness, each having a volume of about 7.25 cm and a closed, rounded end.
  • Protocol for Forming PET Tube (used, e.g., in Examples 2, 4, 8, 9, 10)
  • PET tubes Polyethylene terephthalate (PET) tubes of the type commonly used as evacuated blood collection tubes (“PET tubes”) were injection molded in the same mold used for the Protocol for Forming COC Tube, having these dimensions: 75 mm length, 13 mm outer diameter, and 0.85 mm wall thickness, each having a volume of about 7.25 cm and a closed, rounded end.
  • PET tubes Polyethylene terephthalate
  • the vessel holder 50 was made from Delrin® acetal resin, available from E.I. du Pont de Nemours and Co., Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm).
  • the vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode (160).
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the tube used as the vessel 80 was inserted into the vessel holder 50 base sealing with Viton® O-rings 490, 504 (Viton® is a trademark of DuPont Performance Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube (FIG. 45).
  • the tube 80 was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen 610 was a perforated copper foil material (K&S).
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was 12 holes in the probe or counter electrode 108 along the length of the tube (three on each of four sides oriented 90 degrees from each other) and two holes in the aluminum cap that plugged the end of the gas delivery port 110.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the tube.
  • HMDSO hexamethyldisiloxane
  • the gas system was comprised of a Aalborg® GFC17 mass flow meter (Part # EW- 32661-34, Cole-Parmer Instrument Co., Barrington Illinois USA) for controllably flowing oxygen at 90 seem (or at the specific flow reported for a particular example) into the process and a polyether ether ketone (“PEEK”) capillary (outside diameter, "OD” 1/16-inch (1.5-mm.), inside diameter, "ID” 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m).
  • PEEK capillary end was inserted into liquid hexamethyldisiloxane ("HMDSO," Alfa Aesar® Part Number L16970, NMR Grade, available from Johnson Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to the lower pressure in the tube during processing. The HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
  • HMDSO liquid hexamethyldisi
  • the gas stream (including the oxygen) was diverted to the pumping line when it was not flowing into the interior of the tube for processing via a Swagelok® 3-way valve.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the tube.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system. The pumping system allowed the interior of the tube to be reduced to pressure(s) of less than 200 mTorr while the process gases were flowing at the indicated rates.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream oxygen and HMDSO vapor
  • Pressure inside the tube was approximately 300 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 50 Watts.
  • the RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the tube) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 50 Watts (or the specific amount reported for a particular example) and the reflected power was 0 Watts so that the applied power was delivered to the interior of the tube.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 5 seconds (or the specific time period reported for a particular example). Upon initiation of the RF power, a uniform plasma was established inside the interior of the tube. The plasma was maintained for the entire 5 seconds until the RF power was terminated by the timer.
  • the plasma produced a silicon oxide coating of approximately 20 nm thickness (or the specific thickness reported in a particular example) on the interior of the tube contact surface.
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed. The vent valve was then opened, returning the interior of the tube to atmospheric pressure (approximately 760 Torr). The tube was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • the vessel holder 50 was made from Delrin® acetal resin, available from E.I. du Pont de Nemours and Co., Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm).
  • the vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode (160).
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the tube used as the vessel 80 was inserted into the vessel holder 50 base sealing with Viton® O-rings 490, 504 (Viton® is a trademark of DuPont Performance Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube (FIG. 45).
  • the tube 80 was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen 610 was a perforated copper foil material (K&S).
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was 12 holes in the probe or counter electrode 108 along the length of the tube (three on each of four sides oriented 90 degrees from each other) and two holes in the aluminum cap that plugged the end of the gas delivery port 110.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the tube.
  • HMDSO hexamethyldisiloxane
  • the gas system was comprised of a Aalborg® GFC17 mass flow meter (Part # EW- 32661-34, Cole-Parmer Instrument Co., Barrington Illinois USA) for controllably flowing oxygen at 60 seem (or at the specific flow reported for a particular example) into the process and a polyether ether ketone (“PEEK”) capillary (outside diameter, "OD” 1/16-inch (1.5-mm.), inside diameter, "ID” 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m).
  • PEEK capillary end was inserted into liquid hexamethyldisiloxane ("HMDSO," Alfa Aesar® Part Number L16970, NMR Grade, available from Johnson Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to the lower pressure in the tube during processing. The HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
  • HMDSO liquid hexamethyldisi
  • the gas stream (including the oxygen) was diverted to the pumping line when it was not flowing into the interior of the tube for processing via a Swagelok® 3-way valve.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the tube.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system.
  • the pumping system allowed the interior of the tube to be reduced to pressure(s) of less than 200 mTorr while the process gases were flowing at the indicated rates.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream oxygen and HMDSO vapor
  • Pressure inside the tube was approximately 270 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 39 Watts.
  • the RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the tube) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 39 Watts (or the specific amount reported for a particular example) and the reflected power was 0 Watts so that the applied power was delivered to the interior of the tube.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 7 seconds (or the specific time period reported for a particular example). Upon initiation of the RF power, a uniform plasma was established inside the interior of the tube. The plasma was maintained for the entire 7 seconds until the RF power was terminated by the timer. The plasma produced a silicon oxide coating of approximately 20 nm thickness (or the specific thickness reported in a particular example) on the interior of the tube contact surface.
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed.
  • the vent valve was then opened, returning the interior of the tube to atmospheric pressure (approximately 760 Torr).
  • the tube was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • Syringe barrels (“COC syringe barrels”), CV Holdings Part 11447, each having a 2.8 mL overall volume (excluding the Luer fitting) and a nominal 1 mL delivery volume or plunger displacement, Luer adapter type, were injection molded from Topas® 8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG, Frankfurt am Main, Germany, having these dimensions: about 51 mm overall length, 8.6 mm inner syringe barrel diameter and 1.27 mm wall thickness at the cylindrical portion, with an integral 9.5 millimeter length needle capillary Luer adapter molded on one end and two finger flanges molded near the other end.
  • COC cyclic olefin copolymer
  • An injection molded COC syringe barrel was interior coated with SiOx.
  • the apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45 was modified to hold a COC syringe barrel with butt sealing at the base of the COC syringe barrel.
  • a cap was fabricated out of a stainless steel Luer fitting and a polypropylene cap that sealed the end of the COC syringe barrel (illustrated in FIG. 26), allowing the interior of the COC syringe barrel to be evacuated.
  • the vessel holder 50 was made from Delrin® with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode 160.
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the COC syringe barrel was inserted into the vessel holder 50, base sealing with an Viton® O- rings.
  • the COC syringe barrel was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen was a perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter of the COC syringe barrel and was held in place by a abutment contact surface 494 that acted as a stop for the COC syringe barrel insertion. Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108 insuring good electrical contact.
  • the probe or counter electrode 108 extended approximately 20 mm into the interior of the COC syringe barrel and was open at its end.
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and
  • HMDSO hexamethyldisiloxane
  • the gas system was comprised of a Aalborg® GFC17 mass flow meter (Cole Parmer Part # EW-32661-34) for controllably flowing oxygen at 90 seem (or at the specific flow reported for a particular example) into the process and a PEEK capillary (OD 1/16-inch (3-mm) ID 0.004 inches (0.1 mm)) of length 49.5 inches (1.26 m).
  • the PEEK capillary end was inserted into liquid hexamethyldisiloxane (Alfa Aesar® Part Number L16970, NMR Grade).
  • the liquid HMDSO was pulled through the capillary due to the lower pressure in the COC syringe barrel during processing.
  • the HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the COC syringe barrel.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system.
  • the pumping system allowed the interior of the COC syringe barrel to be reduced to pressure(s) of less than 150 mTorr while the process gases were flowing at the indicated rates.
  • a lower pumping pressure was achievable with the COC syringe barrel, as opposed to the tube, because the COC syringe barrel has a much smaller internal volume.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream oxygen and HMDSO vapor
  • the pressure inside the COC syringe barrel was approximately 200 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 30 Watts.
  • the RF power supply was connected to a COMDEL CPMX1000 auto match that matched the complex impedance of the plasma (to be created in the COC syringe barrel) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 30 Watts (or whatever value is reported in a working example) and the reflected power was 0 Watts so that the power was delivered to the interior of the COC syringe barrel.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 5 seconds (or the specific time period reported for a particular example).
  • a uniform plasma was established inside the interior of the COC syringe barrel.
  • the plasma was maintained for the entire 5 seconds (or other coating time indicated in a specific example) until the RF power was terminated by the timer.
  • the plasma produced a silicon oxide coating of approximately 20 nm thickness (or the thickness reported in a specific example) on the interior of the COC syringe barrel contact surface.
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed.
  • the vent valve was then opened, returning the interior of the COC syringe barrel to atmospheric pressure (approximately 760 Torr).
  • the COC syringe barrel was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • COC syringe barrels as previously identified were interior coated with a lubricity layer.
  • the apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45 was modified to hold a COC syringe barrel with butt sealing at the base of the COC syringe barrel.
  • a cap was fabricated out of a stainless steel Luer fitting and a polypropylene cap that sealed the end of the COC syringe barrel (illustrated in FIG. 26).
  • the installation of a Buna-N O-ring onto the Luer fitting allowed a vacuum tight seal, allowing the interior of the COC syringe barrel to be evacuated.
  • the vessel holder 50 was made from Delrin® with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode 160.
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the COC syringe barrel was inserted into the vessel holder 50, base sealing with Viton® O-rings around the bottom of the finger flanges and lip of the COC syringe barrel.
  • the COC syringe barrel was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen was a perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter of the COC syringe barrel and was held in place by a abutment contact surface 494 that acted as a stop for the COC syringe barrel insertion. Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108 insuring good electrical contact.
  • the probe or counter electrode 108 extended approximately 20mm (unless otherwise indicated) into the interior of the COC syringe barrel and was open at its end.
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gas,
  • OCTS octamethylcyclotetrasiloxane
  • the gas system was comprised of a commercially available Horiba VC1310/SEF8240 OMCTS 10SC 4CR heated mass flow vaporization system that heated the OMCTS to about 100°C.
  • the Horiba system was connected to liquid octamethylcyclotetrasiloxane (Alfa Aesar® Part Number A12540, 98%) through a 1/8-inch (3-mm) outside diameter PFA tube with an inside diameter of 1/16 in (1.5 mm).
  • the OMCTS flow rate was set to 1.25 seem (or the specific organosilicon precursor flow reported for a particular example). To ensure no condensation of the vaporized OMCTS flow past this point, the gas stream was diverted to the pumping line when it was not flowing into the interior of the COC syringe barrel for processing via a Swagelok® 3-way valve.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the COC syringe barrel.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system.
  • the pumping system allowed the interior of the COC syringe barrel to be reduced to pressure(s) of less than 100 mTorr while the process gases were flowing at the indicated rates. A lower pressure could be obtained in this instance, compared to the tube and previous COC syringe barrel examples, because the overall process gas flow rate is lower in this instance.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream (OMCTS vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3-way valve from the pumping line to the gas delivery port 110).
  • Pressure inside the COC syringe barrel was approximately 140 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 6 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 7.5 Watts (or other power level indicated in a specific example).
  • the RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the COC syringe barrel) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 7.5 Watts and the reflected power was 0 Watts so that 7.5 Watts of power (or a different power level delivered in a given example) was delivered to the interior of the COC syringe barrel.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 10 seconds (or a different time stated in a given example).
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed.
  • the vent valve was then opened, returning the interior of the COC syringe barrel to atmospheric pressure (approximately 760 Torr).
  • the COC syringe barrel was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • HMDSO hexamethyldisiloxane
  • O-Si organosilicon
  • COC cyclic olefin copolymer
  • OTR oxygen transmission rate
  • WVTR water vapor transmission rate
  • the uncoated COC tube had an OTR of 0.215 cc/tube/day.
  • Tubes A and B subjected to PECVD for 14 seconds had an average OTR of 0.0235 cc/tube/day.
  • Tube C subjected to PECVD for 7 seconds had an OTR of 0.026.
  • This result shows that the SiO x coating provided an OTR BIF over the uncoated tube of 8.3.
  • the SiO x barrier coating applied in 7 seconds reduced the oxygen transmission through the tube to less than one eighth of its value without the coating.
  • a series of syringe barrels were made according to the Protocol for Forming COC Syringe barrel.
  • the syringe barrels were either barrier coated with SiO x or not under the conditions reported in the Protocol for Coating COC Syringe barrel Interior with SiO x modified as indicated in Table 3.
  • OTR and WVTR samples of the syringe barrels were prepared by epoxy- sealing the open end of each syringe barrel to an aluminum adaptor. Additionally, the syringe barrel capillary ends were sealed with epoxy.
  • the syringe-adapter assemblies were tested for OTR or WVTR in the same manner as the PET tube samples, again using a MOCON® Oxtran 2/21 Oxygen Permeability Instrument and a MOCON® Permatran- W 3/31 Water Vapor Permeability Instrument. The results are reported in Table 3.
  • V.A PET tubes made according to the Protocol for Forming PET Tube and coated according to the Protocol for Coating Tube Interior with SiO x were cut in half to expose the inner tube contact surface, which was then analyzed using X-ray photoelectron spectroscopy (XPS).
  • XPS X-ray photoelectron spectroscopy
  • V.A The XPS data was quantified using relative sensitivity factors and a model which assumes a homogeneous layer.
  • the analysis volume is the product of the analysis area (spot size or aperture size) and the depth of information. Photoelectrons are generated within the X-ray penetration depth (typically many microns), but only the photoelectrons within the top three photoelectron escape depths are detected. Escape depths are on the order of 15-35 A, which leads to an analysis depth of -50-100 A. Typically, 95% of the signal originates from within this depth.
  • V.A. Table 5 provides the atomic ratios of the elements detected.
  • the analytical parameters used in for XPS are as follows:
  • V.A The Inventive Example has an Si/O ratio of 2.4 indicating an SiO x composition, with some residual carbon from incomplete oxidation of the coating. This analysis demonstrates the composition of an SiO x barrier layer applied to a polyethylene terephthalate tube according to the present invention.
  • V.A. Table 4 shows the thickness of the SiO x samples, determined using TEM according to the following method. Samples were prepared for Focused Ion Beam (FIB) cross- sectioning by coating the samples with a sputtered layer of platinum (50-100nm thick) using a K575X Emitech coating system. The coated samples were placed in an FEI FIB200 FIB system. An additional layer of platinum was FIB-deposited by injection of an organo-metallic gas while rastering the 30kV gallium ion beam over the area of interest. The area of interest for each sample was chosen to be a location half way down the length of the tube.
  • FIB Focused Ion Beam
  • Thin cross sections measuring approximately 15 ⁇ ("micrometers") long, 2 ⁇ wide and 15 ⁇ deep were extracted from the die contact surface using a proprietary in-situ FIB lift-out technique.
  • the cross sections were attached to a 200 mesh copper TEM grid using FIB-deposited platinum.
  • One or two windows in each section, measuring about 8 ⁇ wide, were thinned to electron transparency using the gallium ion beam of the FEI FIB.
  • V.C Cross-sectional image analysis of the prepared samples was performed utilizing a Transmission Electron Microscope (TEM). The imaging data was recorded digitally. [00484] The sample grids were transferred to a Hitachi HF2000 transmission electron microscope. Transmitted electron images were acquired at appropriate magnifications. The relevant instrument settings used during image acquisition are given below.
  • TEM Transmission Electron Microscope
  • V.A COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were treated using the Protocol for Coating COC Syringe Barrel Interior with SiO x> with the following variations. Three different modes of plasma generation were tested for coating syringe barrels such as 250 with SiO x films. V.A. In Mode 1, hollow cathode plasma ignition was generated in the gas inlet 310, restricted area 292 and processing vessel lumen 304, and ordinary or non-hollow-cathode plasma was generated in the remainder of the vessel lumen 300.
  • V.A The syringe barrels 250 were then exposed to a ruthenium oxide staining technique.
  • the stain was made from sodium hypochlorite bleach and Ru (III) chloride hydrate.
  • Ru (EI) chloride hydrate was put into a vial. 10ml bleach were added and mixed thoroughly until the Ru(III) chloride hydrate dissolved.
  • V.A Each syringe barrel was sealed with a plastic Luer seal and 3 drops of the staining mixture were added to each syringe barrel. The syringe barrels were then sealed with aluminum tape and allowed to sit for 30-40 minutes. In each set of syringe barrels tested, at least one uncoated syringe barrel was stained. The syringe barrels were stored with the restricted area 292 facing up.
  • V.A. The stain started to attack the uncoated (or poorly coated) areas within 0.25 hours of exposure;
  • V.A. 3 The best syringe barrel was produced by the test with no hollow cathode plasma ignition in either the gas inlet 310 or the restricted area 292. Only the restricted opening 294 was stained, most likely due to leaking of the stain; and
  • V.A Based on all of the above, we concluded: V.A. 1. Under the conditions of the test, hollow cathode plasma in either the gas inlet 310 or the restricted area 292 led to poor uniformity of the coating; and
  • V.A. 2 The best uniformity was achieved with no hollow cathode plasma in either the gas inlet 310 or the restricted area 292.
  • Tungsten 200-1000nm Tungsten 200-1000nm
  • a fiber optic reflection probe combination emitter/collector Ocean Optics QR400-7 SR/BX with approximately 3mm probe area
  • miniature detector Ocean Optics HR4000CG UV-NIR Spectrometer
  • software converting the spectrometer signal to a transmittance/wavelength graph on a laptop computer, an uncoated PET tube Becton Dickinson (Franklin Lakes, New Jersey, USA) Product No.
  • 366703 13x75 mm (no additives) is scanned (with the probe emitting and collecting light radially from the centerline of the tube, thus normal to the coated contact surface) both about the inner circumference of the tube and longitudinally along the inner wall of the tube, with the probe, with no observable interference pattern observed. Then a Becton Dickinson Product No. 366703 13x75 mm (no additives) SiO x plasma- coated BD 366703 tube is coated with a 20 nanometer thick Si0 2 coating as described in Protocol for Coating Tube Interior with SiO x. This tube is scanned in a similar manner as the uncoated tube. A clear interference pattern is observed with the coated tube, in which certain wavelengths were reinforced and others canceled in a periodic pattern, indicating the presence of a coating on the PET tube.
  • VIA The equipment used was a Xenon light source (Ocean Optics HL-2000-HP- FHSA - 20W output Halogen Lamp Source (185-2000nm)), an Integrating Sphere detector (Ocean Optics ISP-80-8-I) machined to accept a PET tube into its interior, and HR2000+ES Enhanced Sensitivity UV.VIS spectrometer, with light transmission source and light
  • receiver fiber optic sources QP600-2-UV-VIS - 600um Premium Optical FIBER, UV/VIS, 2m
  • signal conversion software SPECTRASUITE - Cross-platform Spectroscopy
  • An uncoated PET tube made according to the Protocol for Forming PET Tube was inserted onto a TEFZEL Tube Holder (Puck), and inserted into the integrating sphere. With the Spectrasuite software in absorbance mode, the absorption (at 615nm) was set to zero.
  • An SiOx coated tube made according to the Protocol for Forming PET Tube and coated according to the Protocol for Coating Tube Interior with SiOx was then mounted on the puck, inserted into the integrating sphere and the absorbance recorded at 615nm wavelength. The data is recorded in Table 16.
  • VIA VIA. These spectroscopic methods should not be considered limited by the mode of collection (for example, reflectance vs. transmittance vs. absorbance), the frequency or type of radiation applied, or other parameters.
  • FIG. 30, adapted from FIG. 15 of U.S. Patent 6,584,828, is a schematic view of a test set-up that was used in a working example for measuring outgassing through an SiO x barrier coating 348 applied according to the Protocol for Coating Tube Interior with SiO x on the interior of the wall 346 of a PET tube 358 made according to the Protocol for Forming PET Tube seated with a seal 360 on the upstream end of a Micro-Flow Technology measurement cell generally indicated at 362.
  • VLB VLB.
  • a vacuum pump 364 was connected to the downstream end of a commercially available measurement cell 362 (an Intelligent Gas Leak System with Leak Test Instrument Model ME2, with second generation IMFS sensor, ( ⁇ /min full range), Absolute Pressure Sensor range: 0-10 Torr, Flow measurement uncertainty: +/- 5% of reading, at calibrated range, employing the Leak-Tek Program for automatic data acquisition (with PC) and signatures/plots of leak flow vs. time.
  • This equipment is supplied by ATC Inc.), and was configured to draw gas from the interior of the PET vessel 358 in the direction of the arrows through the measurement cell 362 for determination of the mass flow rate outgassed vapor into the vessel 358 from its walls.
  • VLB The measurement cell 362 shown and described schematically here was understood to work substantially as follows, though this information might deviate somewhat from the operation of the equipment actually used.
  • the cell 362 has a conical passage 368 through which the outgassed flow is directed.
  • the pressure is tapped at two longitudinally spaced lateral bores 370 and 372 along the passage 368 and fed respectively to the chambers 374 and 376 formed in part by the diaphragms 378 and 380.
  • the pressures accumulated in the respective chambers 374 and 376 deflect the respective diaphragms 378 and 380.
  • a bypass 386 can optionally be provided to speed up the initial pump-down by bypassing the measurement cell 362 until the desired vacuum level for carrying out the test is reached.
  • VLB The PET walls 350 of the vessels used in this test were on the order of 1 mm thick, and the coating 348 was on the order of 20 nm (nanometers) thick. Thus, the wall 350 to coating 348 thickness ratio was on the order of 50,000 : 1.
  • VLB To determine the flow rate through the measurement cell 362, including the vessel seal 360, 15 glass vessels substantially identical in size and construction to the vessel 358 were successively seated on the vessel seal 360, pumped down to an internal pressure of 1 Torr, then capacitance data was collected with the measurement cell 362 and converted to an
  • outgassing flow rate The test was carried out two times on each vessel. After the first run, the vacuum was released with nitrogen and the vessels were allowed recovery time to reach equilibrium before proceeding with the second run. Since a glass vessel is believed to have very little outgassing, and is essentially impermeable through its wall, this measurement is understood to be at least predominantly an indication of the amount of leakage of the vessel and connections within the measurement cell 362, and reflects little if any true outgassing or permeation. The results are in Table 7.
  • VLB The family of plots 390 in FIG. 31 shows the "outgas" flow rate, also in micrograms per minute, of individual tubes corresponding to the second run data in previously- mentioned Table 7. Since the flow rates for the plots do not increase substantially with time, and are much lower than the other flow rates shown, the flow rate is attributed to leakage.
  • VLB Table 8 and the family of plots 392 in FIG. 31 show similar data for uncoated tubes made according to the Protocol for Forming PET Tube.
  • VLB This data for uncoated tubes shows much larger flow rates: the increases are attributed to outgas flow of gases captured on or within the inner region of the vessel wall.
  • VLB VLB.
  • Table 9 and the families of plots 394 and 396 in FIG. 31 show similar data for an SiO x barrier coating 348 applied according to the Protocol for Coating PET Tube Interior with SiO x on the interior of the wall 346 of a PET tube made according to the Protocol for Forming PET Tube.
  • VLB The family of curves 394 for the SiO x coated, injection-molded PET tubes of this example shows that the SiO x coating acts as a barrier to limit outgassing from the PET vessel walls, since the flow rate is consistently lower in this test than for the uncoated PET tubes. (The SiO x coating itself is believed to outgas very little.) The separation between the curves 394 for the respective vessels indicates that this test is sensitive enough to distinguish slightly differing barrier efficacy of the SiO x coatings on different tubes.
  • VLB Referring to Tables 8 and 9 previously mentioned and FIG. 32, the data was analyzed statistically to find the mean and the values of the first and third standard deviations above and below the mean (average). These values are plotted in FIG. 32.
  • VLB This statistical analysis also shows the power of an outgassing measurement to very quickly and accurately analyze the barrier efficacy of nano-thickness barrier coatings and to distinguish coated tubes from uncoated tubes (which are believed to be indistinguishable using the human senses at the present coating thickness).
  • This data shows no overlap of the data to a level of certainty exceeding 6 ⁇ (six-sigma).
  • VLB VLB
  • the wetting tension method is a modification of the method described in ASTM D 2578. Wetting tension is a specific measure for the hydrophobicity or hydrophilicity of a contact surface. This method uses standard wetting tension solutions (called dyne solutions) to determine the solution that comes nearest to wetting a plastic film contact surface for exactly two seconds. This is the film's wetting tension.
  • VILA.1.a.ii The procedure utilized is varied from ASTM D 2578 in that the substrates are not flat plastic films, but are tubes made according to the Protocol for Forming PET Tube and (except for controls) coated according to the Protocol for Coating Tube Interior with Hydrophobic layer.
  • a silicone coated glass syringe (Becton Dickinson Hypak® PRTC glass prefillable syringe with Luer-lok® tip) (1 mL) was also tested. The results of this test are listed in Table 10.
  • VH.A. l.a.ii Surprisingly, plasma coating of uncoated PET tubes (40 dynes/cm) can achieve either higher (more hydrophilic) or lower (more hydrophobic) energy contact surfaces using the same hexamethyldisiloxane (HMDSO) feed gas, by varying the plasma process conditions.
  • a thin (approximately 20-40 nanometers) SiO x coating made according to the Protocol for Coating Tube Interior with SiO x (data not shown in the tables) provides similar wettability as hydrophilic bulk glass substrates.
  • a thin (less than about 100 nanometers) hydrophobic layer made according to the Protocol for Coating Tube Interior with Hydrophobic layer provides similar non- wettability as hydrophobic silicone fluids (data not shown in the tables).
  • PET tubes made according to the Protocol for Forming PET Tube, closed with the same type of Hemogard® system red stopper and uncolored guard [internal control];
  • Water volume draw change determinations were made by (a) removing 3-5 samples at increasing time intervals, (b) permitting water to draw into the evacuated tubes through a 20 gauge blood collection adaptor from a one liter plastic bottle reservoir, (c) and measuring the mass change before and after water draw.
  • VH.B.l.a The jig was installed on the Dillon Test Stand. The platform probe movement was adjusted to 6 in/min (2.5 mm/sec) and upper and lower stop locations were set. The stop locations were verified using an empty syringe and barrel. The commercial saline- filled syringes were labeled, the plungers were removed, and the saline solution was drained via the open ends of the syringe barrels for re-use. Extra plungers were obtained in the same manner for use with the COC and glass barrels.
  • VH.B.l.a Syringe plungers were inserted into the COC syringe barrels so that the second horizontal molding point of each plunger was even with the syringe barrel lip (about 10 mm from the tip end).
  • the test syringes were filled via the capillary end with 2-3 milliliters of saline solution, with the capillary end uppermost. The sides of the syringe were tapped to remove any large air bubbles at the plunger/ fluid interface and along the walls, and any air bubbles were carefully pushed out of the syringe while maintaining the plunger in its vertical orientation.
  • VH.B.l.a Each filled syringe barrel/plunger assembly was installed into the syringe jig. The test was initiated by pressing the down switch on the test stand to advance the moving metal hammer toward the plunger. When the moving metal hammer was within 5mm of contacting the top of the plunger, the data button on the Dillon module was repeatedly tapped to record the force at the time of each data button depression, from before initial contact with the syringe plunger until the plunger was stopped by contact with the front wall of the syringe barrel.
  • VH.B.l.a All benchmark and coated syringe barrels were run with five replicates (using a new plunger and barrel for each replicate).
  • VH.B.l.a COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were coated with an OMCTS lubricity layer according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer, assembled and filled with saline, and tested as described above in this Example for lubricity layers.
  • the polypropylene chamber used per the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer allowed the OMCTS vapor (and oxygen, if added - see Table 13) to flow through the syringe barrel and through the syringe capillary into the polypropylene chamber (although a lubricity layer can not be needed in the capillary section of the syringe in this instance).
  • OMCTS vapor and oxygen, if added - see Table 13
  • Table 13 Several different coating conditions were tested, as shown in previously mentioned Table 13. All of the depositions were completed on COC syringe barrels from the same production batch.
  • VH.B.l.a The samples were created by coating COC syringe barrels according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer.
  • VH.B.l.a The force required to expel a 0.9 percent saline payload from a syringe through a capillary opening using a plastic plunger was determined for inner wall-coated syringes.
  • VH.B.l.a Three types of COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were tested: one type having no internal coating [Uncoated Control], another type with a hexamethyldisiloxane (HMDSO)-based plasma coated internal wall coating [HMDSO Control] according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating, and a third type with an octamethylcyclotetrasiloxane [OMCTS - Inventive Example] -based plasma coated internal wall coating applied according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer.
  • Fresh plastic plungers with elastomeric tips taken from BD Product Becton-Dickinson Product No. 306507 were used for all examples. Saline from Product No. 306507 was also used.
  • VH.B.l.a The plasma coating method and apparatus for coating the syringe barrel inner walls is described in other experimental sections of this application.
  • the specific coating parameters for the HMDSO-based and OMCTS-based coatings are listed in the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating, the Protocol for Coating COC Syringe barrel Interior with OMCTS Lubricity layer, and Table 14.
  • VH.B.l.a The plunger is inserted into the syringe barrel to about 10 millimeters, followed by vertical filling of the experimental syringe through the open syringe capillary with a separate saline-filled syringe/needle system.
  • the syringe is tapped to permit any air bubbles adhering to the inner walls to release and rise through the capillary opening.
  • VH.B.l.a The filled experimental syringe barrel/plunger assembly is placed vertically into a home-made hollow metal jig, the syringe assembly being supported on the jig at the finger flanges.
  • the jig has a drain tube at the base and is mounted on Dillon Test Stand with Advanced Force Gauge (Model AFG-50N).
  • the test stand has a metal hammer, moving vertically downward at a rate of six inches (152 millimeters) per minute. The metal hammer contacts the extended plunger expelling the saline solution through the capillary. Once the plunger has contacted the syringe barrel/capillary interface the experiment is stopped.
  • VH.B.l.a During downward movement of the metal hammer/extended plunger, resistance force imparted on the hammer as measured on the Force Gauge is recorded on an electronic spreadsheet. From the spreadsheet data, the maximum force for each experiment is identified.
  • VH.B.l.a Table 14 lists for each Example the Maximum Force average from replicate coated COC syringe barrels and the Normalized Maximum Force as determined by division of the coated syringe barrel Maximum Force average by the uncoated Maximum Force average.
  • VII.B.1.a The data indicates all OMCTS-based inner wall plasma coated COC syringe barrels (Inventive Examples C,E,F,G,H) demonstrate much lower plunger sliding force than uncoated COC syringe barrels (uncoated Control Examples A & D) and surprisingly, also much lower plunger sliding force than HMDSO-based inner wall plasma coated COC syringe barrels (HMDSO control Example B).
  • an OMCTS-based coating over a silicon oxide (SiO x ) gas barrier coating maintains excellent low plunger sliding force (Inventive Example F).
  • a COC syringe barrel formed according to the Protocol for Forming COC Syringe barrel is sealed at both ends with disposable closures.
  • the capped COC syringe barrel is passed through a bath of Daran® 8100 Saran Latex (Owensboro Specialty Plastics). This latex contains five percent isopropyl alcohol to reduce the contact surface tension of the composition to 32 dynes/cm).
  • the latex composition completely wets the exterior of the COC syringe barrel.
  • the coated COC syringe barrel is exposed to a heating schedule comprising 275°F (135°C) for 25 seconds (latex coalescence) and 122°F (50°C) for four hours (finish cure) in respective forced air ovens.
  • the resulting PVdC film is 1/10 mil (2.5 microns) thick.
  • the COC syringe barrel and PVdC-COC laminate COC syringe barrel are measured for OTR and WVTR using a MOCON brand Oxtran 2/21 Oxygen Permeability Instrument and Permatran- W 3/31 Water Vapor Permeability Instrument, respectively.
  • COC syringe barrel samples made according to the Protocol for Forming COC Syringe barrel, coated with OMCTS (according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer) or coated with HMDSO according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating were provided.
  • the atomic compositions of the coatings derived from OMCTS or HMDSO were characterized using X-Ray Photoelectron Spectroscopy (XPS).
  • XPS data is quantified using relative sensitivity factors and a model that assumes a homogeneous layer.
  • the analysis volume is the product of the analysis area (spot size or aperture size) and the depth of information. Photoelectrons are generated within the X-ray penetration depth (typically many microns), but only the photoelectrons within the top three photoelectron escape depths are detected. Escape depths are on the order of 15-35 A, which leads to an analysis depth of -50-100 A. Typically, 95% of the signal originates from within this depth.
  • VII.B.4 Table 17 provides the atomic concentrations of the elements detected. XPS does not detect hydrogen or helium. Values given are normalized to 100 percent using the elements detected. Detection limits are approximately 0.05 to 1.0 atomic percent. [00544] VII.B.4. From the coating composition results and calculated starting monomer precursor elemental percent in Table 17, while the carbon atom percent of the HMDSO-based coating is decreased relative to starting HMDSO monomer carbon atom percent (54.1% down to 44.4%), surprisingly the OMCTS-based coating carbon atom percent is increased relative to the OMCTS monomer carbon atom percent (34.8% up to 48.4%), an increase of 39 atomic %, calculated as follows:
  • COC syringe barrel samples made according to the Protocol for Forming COC Syringe barrel, coated with OMCTS (according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer) or with HMDSO (according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating) were provided.
  • Outgassing gas chromatography/mass spectroscopy (GC/MS) analysis was used to measure the volatile components released from the OMCTS or HMDSO coatings.
  • MSD Mass Selective Detector
  • HMDSO-based compositions outgassed trimethylsilanol [(Me) 3 SiOH] but outgassed no measured higher oligomers containing repeating -(Me) 2 SiO- moieties
  • OMCTS-based compositions outgassed no measured trimethylsilanol [(Me ⁇ SiOH] but outgassed higher oligomers containing repeating -(Me) 2 SiO- moieties. It is contemplated that this test can be useful for differentiating HMDSO-based coatings from OMCTS-based coatings.
  • OMCTS is contemplated to react by ring opening to form a diradical having repeating -(Me) 2 SiO- moieties which are already oligomers, and can condense to form higher oligomers.
  • HMDSO is contemplated to react by cleaving at one O-Si bond, leaving one fragment containing a single O-Si bond that recondenses as (Me ⁇ SiOH and the other fragment containing no O-Si bond that recondenses as [(Me) 3 Si] 2 .
  • the cyclic nature of OMCTS is believed to result in ring opening and condensation of these ring-opened moieties with outgassing of higher MW oligomers (26 ng/test).
  • HMDSO-based coatings are believed not to provide any higher oligomers, based on the relatively low-molecular- weight fragments from HMDSO.
  • HMDSO-based and OMCTS-based coatings there is a fundamental difference in reaction mechanism in the formation of the respective HMDSO-based and OMCTS-based coatings.
  • HMDSO fragments can more easily nucleate or react to form dense nanoparticles which then deposit on the contact surface and react further on the contact surface, whereas OMCTS is much less likely to form dense gas phase nanoparticles.
  • OMCTS reactive species are much more likely to condense on the contact surface in a form much more similar to the original OMCTS monomer, resulting in an overall less dense coating.
  • COC tubes were made according to the Protocol for Forming COC Tube. Some of the tubes were provided with an interior barrier coating of SiOx according to the Protocol for Coating Tube Interior with SiO x , and other COC tubes were uncoated. Commercial glass blood collection Becton Dickinson 13 x 75 mm tubes having similar dimensions were also provided as above. The tubes were stored for about 15 minutes in a room containing ambient air at 45% relative humidity and 70 ° F (21 ° C), and the following testing was done at the same ambient relative humidity.
  • Example 8 an Intelligent Gas Leak System with Leak Test Instrument Model ME2, with second generation IMFS sensor, ( ⁇ /min full range), Absolute Pressure Sensor range: 0-10 Torr, Flow measurement uncertainty: +/- 5% of reading, at calibrated range, employing the Leak-Tek Program for automatic data acquisition (with PC) and signatures/plots of leak flow vs. time).
  • each tube was subjected to a 22- second bulk moisture degassing step at a pressure of 1 mm Hg, was pressurized with nitrogen gas for 2 seconds (to 760 millimeters Hg), then the nitrogen gas was pumped down and the microflow measurement step was carried out for about one minute at 1 millimeter Hg pressure.

Abstract

A method of making an antimicrobial medical device is described. A medical device or material or portion thereof is provided comprising a contact surface. A first treatment of SiOx, SiOxCy, or SiNxCy is applied to the contact surface. Before or after the first treatment, a second antimicrobially effective treatment is applied to the contact surface. The second treatment is a treatment of a metal selected from silver (preferred), gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment. Medical devices or their parts made according to the above process are also described.

Description

ANTIMICROBIAL TREATMENT OF MEDICAL DEVICE SURFACES
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 61/808,272, filed April 4, 2013. The entire specification and all the drawings of the provisional application are incorporated here by reference to provide continuity of disclosure.
BACKGROUND
[0002] The invention concerns an improved medical device comprising: a surface which is configured to contact a human or animal fluid or tissue or a pharmaceutical preparation; and silver ions or other antimicrobial material coated in or incorporated on the surface in an amount effective to inhibit microbial growth on or adjacent to the surface.
[0003] Nosocomial, or hospital-related bacterial infections, are estimated to be the fifth- leading cause of death in the United States, after heart disease, cancer, stroke, and pneumonia or flu. The Centers for Disease Control estimate that nosocomial infections cost hospitals more than $2300 per patient for diagnosis and treatment. Many instances, such as vascular catheter infection, can cost $25,000 per episode. Overall, the infections cost hospitals $4.8 billion annually in extended care and treatment.
[0004] Pathogens mutate quickly and render antibiotics useless in fighting them. A great majority of healthcare-acquired infections involve many of the pathogens displaying
antimicrobial resistance. Therefore, silver's medicinal importance in combating these infections cannot be underestimated.
[0005] Silver is effective across a broad range of bacteria and against mutating pathogens. It is also effective in blocking fungi and yeasts known to cause disease.
[0006] Silver is harmless to the body at bacterial effective levels. Humans take in about
70-88 μg of silver each day. Other heavy metals, such as mercury and lead, can bond chemically and accumulate in the body, which can inhibit metabolism. By contrast, research suggests that 99% of silver is readily excreted. Silver is, for the most part, nontoxic. Cases of extreme exposure have caused upper respiratory or mild eye irritation, and prolonged exposure can cause argyria. However, silver oxide is an effective antimicrobial at levels as little as 1 ppm, so toxicity concerns are mostly irrelevant.
[0007] During the early 20th century, before the advent of antibiotics, silver was rediscovered as an antimicrobial agent from ancient times. However, use of metallic silver had inherent problems. Metallic silver can stain tissues and interfere with wound assessment. It also has a short shelf life requiring frequent reapplications to provide continuous antimicrobial activity. Metallic silver is biologically inert and passes through the body. In order to exhibit antimicrobial effects, silver must be in an ionic state. Ionic silver is a single atom missing one orbital electron. The antimicrobial character requires water to activate. Today, the use of silver oxide rather than metallic silver has eliminated these problems. However, application issues continue to emerge, and manufacturers continue to look for better techniques.
[0008] Manufacturers currently use silver oxide antimicrobial technologies. These methods include traditional coating technologies, silver ion incorporation into material compounds, and surface-engineered nanostructures. Each of these categories attempts to address the problems inherent in silver oxide antimicrobial applications with varying results.
[0009] U.S. Published Patent Application 2006-0198903 Al [Storey et al.] states that it relates to "efficient methods for depositing highly adherent anti-microbial materials onto a wide range of surfaces. A controlled cathodic arc process is described, which results in enhanced adhesion of silver oxide to polymers and other surfaces, such as surfaces of medical devices. Deposition of anti-microbial materials directly onto the contact surfaces is possible in a cost- effective manner that maintains high anti-microbial activity over several weeks when the coated devices are employed in vivo." This application is hereby incorporated by reference in its entirety here. See also PCT Published Application WO03044240A1.
[0010] Storey et al. also identifies several alternative metals for antimicrobial use: gold, platinum, copper, tantalum, titanium, zirconium, hafnium, and zinc. Storey et al. identifies a metal or polymeric surface as potential contact surfaces for antimicrobial treatment, and states that "the Ag/AgO impregnates the metal contact surface up to a depth of about 10 nanometers," and a polymeric contact surface "up to a depth of about 100 nanometers." Exemplary polymeric contact surfaces identified are: "polypropylene, polyurethane, EPTFE, PTFE, polyimide, polyester, PEEK, UHMWPE, and nylon." [0011] Storey et al. identifies the following types of medical devices as potentially benefitting from such treatment: "catheters, valves, stents and implants;"
[0012] Storey also mentions the following contact surfaces as potentially benefitting from antimicrobial treatment: "surgical and wound dressings and bandages, surgical sutures, catheters and other medical devices, implants, prosthetics, dental applications and tissue regeneration medical tools and surfaces, restaurant surfaces, face masks, clothing, door knobs and other fixtures, swimming pools, hot tubs, drinking water filters, cooling systems, porous hydrophilic materials, humidifiers and air handling systems." "Such medical devices include catheters, implants, stents, tracheal tubes, orthopedic pins, shunts, drains, prosthetic devices, dental implants, dressings and wound closures. However, it should be understood that the invention is not limited to such devices and may extend to other devices useful in the medical field, such as face masks, clothing, surgical tools and surfaces." Storey et al. is hereby incorporated by reference in its entirety here for its disclosure of antimicrobial silver application techniques.
[0013] Bruce Gibbins and Lenna Warner, The Role of Antimicrobial Silver
Nanotechnology, MEDICAL DEVICE & DIAGNOSTIC INDUSTRY, Aug. 2005, pp. 2-6, at p.4
[Gibbins et al.], states, "Biofilm formation is extremely difficult to eliminate once it has begun. Preventing biofilms on medical devices and implants is key to controlling their contribution to establishing infection. Because biofilm formation is dependent upon a surface, one strategy is to modify the surface to make it hostile to microorganisms. Ionic silver is becoming a favored substance for surface modification for a number of reasons, including the following: [0014] "It has broad-spectrum antimicrobial action.
[0015] "It is well tolerated by tissues.
[0016] "It is compatible with most materials used in making medical devices.
[0017] "It can be compounded into the submatrix or applied on the surface, and resistance to it is largely nonexistent."
[0018] Gibbins et al. goes on to identify technologies said to be useful for incorporating silver as nanoparticles, stating: "Nanosilver particles (as small as 1000th the diameter of a bacterium) constitute the reservoir for the antimicrobial effect." "Several methods are used to enable silver antimicrobial nanotechnologies to adhere to the surface of a medical device.
Typically, vacuum- sputter coating and plasma-arc deposition technologies direct vaporized silver at the device surface. * * * Ionic Plasma Deposition (IPD) ... silver antimicrobial nanotechnology is effective against pathogens associated with biofilms including Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, and Asperigus niger." Gibbins et al. is hereby incorporated by reference in its entirety here for its disclosure of antimicrobial silver application techniques.
[0019] Commonly owned U.S. Published Patent Application 2010-0298738 [Felts et al.] discloses improved medical devices such as vessels, for example syringes and syringe parts, blood and other sample collection tubes, vials, cuvettes, etc.. These medical devices are made of injection molded polymers or glass, then coated using plasma enhanced chemical vapor deposition (PECVD) with SiOx, SiOxCyHz, SiNxCyHz, and other materials. The coatings provide one or more of a gas barrier, lubricity, a modification of the surface properties of the contact surface (such as to make it more hydrophilic or hydrophobic than the contact surface) or other benefits.
SUMMARY OF THE INVENTION
[0020] An aspect of the present invention is a method of making an antimicrobial medical device. In the method, a medical device or material or portion thereof is provided comprising a contact surface. A first treatment of SiOx, SiOxCy, or SiNxCy is applied to the contact surface. Before or after the first treatment, a second antimicrobially effective treatment is applied to the contact surface. The second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
[0021] Medical devices or their parts made according to the above process are another aspect of the invention.
[0022] Other aspects of the invention will be apparent from this disclosure and the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 is a schematic diagram showing a vessel processing system according to an embodiment of the disclosure.
[0024] FIG. 2 is a schematic sectional view of a vessel holder in a coating station according to an embodiment of the disclosure.
[0025] FIG. 3 is a view similar to FIG. 2 of an alternative embodiment of the disclosure.
[0026] FIG. 4 is a diagrammatic plan view of an alternative embodiment of the vessel holder.
[0027] FIG. 5 is a diagrammatic plan view of another alternative embodiment of the vessel holder.
[0028] FIG. 6 is a view similar to FIG. 2 of vessel inspection apparatus.
[0029] FIG. 7 is a view similar to FIG. 2 of alternative vessel inspection apparatus.
[0030] FIG. 8 is a section taken along section lines A— A of FIG. 2.
[0031] FIG. 9 is an alternative embodiment of the structure shown in FIG. 8.
[0032] FIG. 10 is a view similar to FIG. 2 of a vessel holder in a coating station according to another embodiment of the disclosure, employing a CCD detector.
[0033] FIG. 11 is a detail view similar to FIG. 10 of a light source and detector that are reversed compared to the corresponding parts of FIG. 6.
[0034] FIG. 12 is a view similar to FIG. 2 of a vessel holder in a coating station according to still another embodiment of the disclosure, employing microwave energy to generate the plasma.
[0035] FIG. 13 is a view similar to FIG. 2 of a vessel holder in a coating station according to yet another embodiment of the disclosure, in which the vessel can be seated on the vessel holder at the process station.
[0036] FIG. 14 is a view similar to FIG. 2 of a vessel holder in a coating station according to even another embodiment of the disclosure, in which the electrode can be configured as a coil.
[0037] FIG. 15 is a view similar to FIG. 2 of a vessel holder in a coating station according to another embodiment of the disclosure, employing a tube transport to move a vessel to and from the coating station. [0038] FIG. 16 is a diagrammatic view of the operation of a vessel transport system, such as the one shown in FIG. 15, to place and hold a vessel in a process station.
[0039] FIG. 17 is a diagrammatic view of a mold and mold cavity for forming a vessel according to an aspect of the present disclosure.
[0040] FIG. 18 is a diagrammatic view of the mold cavity of FIG. 17 provided with a vessel coating device according to an aspect of the present disclosure.
[0041] FIG. 19 is a view similar to FIG. 17 provided with an alternative vessel coating device according to an aspect of the present disclosure.
[0042] FIG. 20 is an exploded longitudinal sectional view of a syringe and cap adapted for use as a prefilled syringe.
[0043] FIG. 21 is a view generally similar to FIG. 2 showing a capped syringe barrel and vessel holder in a coating station according to an embodiment of the disclosure.
[0044] FIG. 22 is a view generally similar to FIG. 21 showing an uncapped syringe barrel and vessel holder in a coating station according to yet another embodiment of the invention.
[0045] FIG. 23 is a perspective view of a blood collection tube assembly having a closure according to still another embodiment of the invention.
[0046] FIG. 24 is a fragmentary section of the blood collection tube and closure assembly of FIG. 23.
[0047] FIG. 25 is an isolated section of an elastomeric insert of the closure of FIGS. 23 and 24.
[0048] FIG. 26 is a view similar to FIG. 22 of another embodiment of the invention for processing syringe barrels and other vessels.
[0049] FIG. 27 is an enlarged detail view of the processing vessel of FIG. 26.
[0050] FIG. 28 is a schematic view of an alternative processing vessel.
[0051] FIG. 29 is a schematic view showing outgassing of a material through a coating. [0052] FIG. 30 is a schematic sectional view of a test set-up for causing outgassing of the wall of a vessel to the interior of the vessel and measurement of the outgassing using a measurement cell interposed between the vessel and a source of vacuum.
[0053] FIG. 31 is a plot of outgassing mass flow rate measured on the test-set-up of FIG. 30 for multiple vessels.
[0054] FIG. 32 is a bar graph showing a statistical analysis of the endpoint data shown in FIG. 31.
[0055] FIG. 33 is a longitudinal section of a combined syringe barrel and gas receiving volume according to another embodiment of the invention.
[0056] FIG. 34 is a view similar to FIG 34 of another embodiment of the invention including an electrode extension.
[0057] FIG. 35 is a view taken from section lines 35 - 35 of FIG. 34, showing the distal gas supply openings and extension electrode of FIG. 34.
[0058] FIG. 36 is a perspective view of a double-walled blood collection tube assembly according to still another embodiment of the invention.
[0059] FIG. 37 is a view similar to FIG. 22 showing another embodiment.
[0060] FIG. 38 is a view similar to FIG. 22 showing still another embodiment.
[0061] FIG. 39 is a view similar to FIG. 22 showing yet another embodiment.
[0062] FIG. 40 is a view similar to FIG. 22 showing even another embodiment.
[0063] FIG. 41 is a plan view of the embodiment of FIG. 40.
[0064] FIG. 42 is a fragmentary detail longitudinal section of an alternative sealing arrangement, usable for example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12- 16, 18, 19, 33, and 37-41 for seating a vessel on a vessel holder. FIG. 42 also shows an alternative syringe barrel construction usable, for example, with the embodiments of FIGS. 2, 3, 6-10, 12-22, 26-28, 33- 34, and 37-41.
[0065] FIG. 43 is a further enlarged detail view of the sealing arrangement shown in FIG. 42. [0066] FIG. 44 is a view similar to FIG. 2 of an alternative gas delivery tube/inner electrode usable, for example with the embodiments of FIGS. 1, 2, 3, 8, 9, 12-16, 18-19, 21-22, 33, 37-43, 46-49, and 52-54.
[0067] FIG. 45 is an alternative construction for a vessel holder usable, for example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12-16, 18, 19, 21, 22, 26, 28, 33-35, and 37-44.
[0068] FIG. 46 is a schematic sectional view of an array of gas delivery tubes and a mechanism for inserting and removing the gas delivery tubes from a vessel holder, showing a gas delivery tube in its fully advanced position.
[0069] FIG. 47 is a view similar to FIG. 46, showing a gas delivery tube in an intermediate position.
[0070] FIG. 48 is a view similar to FIG. 46, showing a gas delivery tube in a retracted position. The array of gas delivery tubes of FIGS. 46-48 are usable, for example, with the embodiments of FIGS. 1, 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-45, 49, and 52-54. The mechanism of FIGS. 46-48 is usable, for example, with the gas delivery tube embodiments of FIGS. 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-45, 49, and 52-54, as well as with the probes of the vessel inspection apparatus of FIGS. 6 and 7.
[0071] FIG. 49 is a view similar to FIG. 16 showing a mechanism for delivering vessels to be treated and a cleaning reactor to a PECVD coating apparatus. The mechanism of FIG. 49 is usable with the vessel inspection apparatus of FIGS. 1, 9, 15, and 16, for example.
[0072] FIG. 50 is an exploded view of a two-piece syringe barrel and Luer lock fitting. The syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-22, 26-28, 33-35, 37-39, 44, and 53-54.
[0073] FIG. 51 is an assembled view of the two-piece syringe barrel and Luer lock fitting of FIG. 50.
[0074] FIG. 52 is a view similar to FIG. 42 showing a syringe barrel being treated that has no flange or finger stops 440. The syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-51, and 53-54.
[0075] FIG. 53 is a schematic view of an assembly for treating vessels. The assembly is usable with the apparatus of FIGS. 1-3, 8-9, 12-16, 18-22, 26-28, 33-35, and 37-49. [0076] FIG. 54 is a diagrammatic view of the embodiment of FIG. 53.
[0077] FIG. 55 is a diagrammatic view similar to FIG. 2 of an embodiment of the invention including a plasma screen.
[0078] FIG. 56 is a schematic sectional view of an array of gas delivery tubes, having independent gas supplies and a mechanism for inserting and removing the gas delivery tubes from a vessel holder.
[0079] FIG. 57 is a plot of outgassing mass flow rate measured in Example 19.
[0080] FIG. 58 shows a linear rack, otherwise similar to FIG. 4.
[0081] FIG. 59 shows a schematic representation of a vessel processing system according to an exemplary embodiment of the present invention.
[0082] FIG. 60 shows a schematic representation of a vessel processing system according to another exemplary embodiment of the present invention.
[0083] FIG. 61 shows a processing station of a vessel processing system according to an exemplary embodiment of the present invention.
[0084] FIG. 62 shows a portable vessel holder according to an exemplary embodiment of the present invention.
[0085] The following reference characters are used in the drawing figures:
Vessel processing system 94 Vacuum duct
Injection molding machine 96 Vacuum port
Visual inspection station 98 Vacuum source
Inspection station (pre- 100 O-ring (of 92)
coating) 102 O-ring (of 96)
Coating station
104 Gas inlet port
Inspection station (post-
106 O-ring (of 100) coating)
Optical source transmission 108 Probe (counter electrode) station (thickness) 110 Gas delivery port (of 108)
Optical source transmission 112 Vessel holder (Fig. 3) station (defects) 114 Housing (of 50 or 112)
Output
116 Collar
Vessel holder Exterior contact surface (of
Vessel holder 118
80)
Vessel holder 120 Vessel holder (array)
Vessel holder 122 Vessel port (Fig. 4, 58)
Vessel holder 130 Frame (Fig. 5)
Vessel holder 132 Light source
Vessel holder 134 Side channel
Vessel holder 136 Shut-off valve
Vessel holder 138 Probe port
Vessel holder 140 Vacuum port
Vessel holder 142 PECVD gas inlet port
Vessel holder 144 PECVD gas source
Vessel holder 146 Vacuum line (to 98)
Vessel holder 148 Shut-off valve
Vessel holder 150 Flexible line (of 134)
Vessel holder 152 Pressure gauge
Conveyor 154 Interior of vessel 80
Transfer mechanism (on) 160 Electrode
Transfer mechanism (off) 162 Power supply
Vessel 164 Sidewall (of 160)
Opening 166 Sidewall (of 160)
Closed end 168 Closed end (of 160)
Wall 170 Light source (Fig. 10)
Interior contact surface 172 Detector
Barrier layer 174 Pixel (of 172)
Vessel port
Figure imgf000012_0001
type) 326 Vessel opening (of 324) 394 Main plot (Si02 coated)
328 Second opening (of 324) 396 Outliers (Si02 coated)
330 Vacuum port (receiving 328) Inner electrode and gas supply
398
332 First fitting (male Luer taper) tube
Second fitting (female Luer 400 Distal opening
334
taper) 402 Extension counter electrode
336 Locking collar (of 332) 404 Vent (Fig. 7)
338 First abutment (of 332) 406 Valve
340 Second abutment (of 332) 408 Inner wall (Fig. 36)
342 O-ring 410 Outer wall (Fig. 36)
344 Dog Interior contact surface (Fig.
412
346 Wall 36)
414 Plate electrode (Fig. 37)
348 Coating (on 346)
416 Plate electrode (Fig. 37)
350 Permeation path
418 Vacuum conduit
352 Vacuum
420 Vessel holder
354 Gas molecule
422 Vacuum chamber
355 Gas molecule
Interface (between 346 and 424 Vessel holder
356
348) 426 Counter electrode
357 Gas molecule 428 Vessel holder (Fig. 39)
358 PET vessel 430 Electrode assembly
359 Gas molecule 432 Volume enclosed by 430
360 Seal 434 Pressure proportioning valve
362 Measurement cell 436 Vacuum chamber conduit
364 Vacuum pump 438 Syringe barrel (Fig. 42)
366 Arrows 440 Flange (of 438)
368 Conical passage 442 Back opening (of 438)
370 Bore 444 Barrel wall (of 438)
372 Bore 450 Vessel holder (Fig 42)
374 Chamber 452 Annular lip
376 Chamber Generally cylindrical sidewall
454
378 Diaphragm (of 438)
Generally cylindrical inner
380 Diaphragm 456
contact surface (of 450)
382 Conductive contact surface 458 Abutment
384 Conductive contact surface 460 Pocket
386 Bypass 462 O-ring
390 Plot (glass tube) 464 Outside wall (of 460)
392 Plot (PET uncoated) 466 Bottom wall (of 460) 468 Top wall (of 460) 539 Solute retainer
470 Inner electrode (Fig. 44) 540 Open end (of 532)
472 Distal portion (of 470) 542 Interior space (of 532)
474 Porous side wall (of 472) 544 Syringe
476 Internal passage (of 472) 546 Plunger
478 Proximal portion (of 470) 548 Body
480 Distal end (of 470) 550 Barrel
482 Vessel holder body Interior contact surface (of
552
484 Upper portion (of 482) 550)
554 Coating
486 Base portion (of 482)
556 Luer fitting
488 Joint (between 484 and 486)
558 Luer taper
490 O-ring
560 Internal passage (of 558)
492 Annular pocket
Radially extending abutment 562 Internal contact surface
494
contact surface 564 Coupling
496 Radially extending wall 566 Male part (of 564)
498 Screw 568 Female part (of 564)
500 Screw 570 Barrier layer
502 Vessel port 572 Locking collar
504 Second O-ring 574 Main vacuum valve
506 Inner diameter (of 490) 576 Vacuum line
508 Vacuum duct (of 482) 578 Manual bypass valve
510 Inner electrode 580 Bypass line
512 Inner electrode 582 Vent valve
Insertion and removal
514 584 Main reactant gas valve
mechanism 586 Main reactant feed line
516 Flexible hose
588 Organosilicon liquid reservoir
518 Flexible hose Organosilicon feed line
520 Flexible hose 590
(capillary)
522 Valve 592 Organosilicon shut-off valve
524 Valve 594 Oxygen tank
526 Valve 596 Oxygen feed line
528 Electrode cleaning station 598 Mass flow controller
530 Inner electrode drive 600 Oxygen shut-off valve
532 Cleaning reactor 602 Syringe exterior barrier layer
534 Vent valve 604 Lumen
536 Second gripper 606 Barrel exterior contact surface
538 Conveyer 610 Plasma screen 612 Plasma screen cavity
614 Headspace
616 Pressure source
618 Pressure line
620 Capillary connection
630 Plots for uncoated COC
632 Plots for SiOx coated COC
634 Plots for glass
5501 First processing station
5502 Second processing station
5503 Third processing station
5504 Fourth processing station
5505 Processor
5506 User interface
5507 Bus
5701 PECVD apparatus
5702 First detector
5703 Second detector
5704 Detector
5705 Detector
5706 Detector
5707 Detector
7001 Conveyor exit branch
7002 Conveyor exit branch
7003 Conveyor exit branch
7004 Conveyor exit branch
DEFINITION SECTION
[0086] In the context of the present invention, the following definitions and abbreviations are used:
[0087] RF is radio frequency; seem is standard cubic centimeters per minute.
[0088] The term "at least" in the context of the present invention means "equal or more" than the integer following the term. The word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality unless indicated otherwise.
[0089] "First" and "second" or similar references to, e.g., processing stations or processing devices refer to the minimum number of processing stations or devices that are present, but do not necessarily represent the order or total number of processing stations and devices. These terms do not limit the number of processing stations or the particular processing carried out at the respective stations.
[0090] For purposes of the present invention, an "organosilicon precursor" is a compound having at least one of the linkage:
I
-O-Si-C-H
I which is a tetravalent silicon atom connected to an oxygen atom and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom). A volatile organosilicon precursor, defined as such a precursor that can be supplied as a vapor in a PECVD apparatus, is an optional organosilicon precursor. Optionally, the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors.
[0091] [405] In the context of the present invention, "essentially no oxygen" or
(synonymously) "substantially no oxygen" is added to the gaseous reactant in some
embodiments. This means that some residual atmospheric oxygen can be present in the reaction space, and residual oxygen fed in a previous step and not fully exhausted can be present in the reaction space, which are defined here as essentially no oxygen present. Essentially no oxygen is present in the gaseous reactant if the gaseous reactant comprises less than 1 vol 02, for example less than 0.5 vol 02, and optionally is 02-free. If no oxygen is added to the gaseous reactant, or if no oxygen at all is present during PECVD, this is also within the scope of
"essentially no oxygen."
[0092] The invention has particular application to "contact surfaces" of medical devices and the like used or usable in contact with human or animal fluids or tissues, whether or not associated with a vessel.
[0093] One category of contact surfaces is vessels. A "vessel" in the context of the present invention can be any type of article that is adapted to contain or convey a material. The material can be a liquid, a gas, a solid, or any two or more of these. One example of a vessel is an article with at least one opening and a wall defining an interior contact surface. Optionally, at least a portion of the interior contact surface defines a "contact surface" which is treated according to the present disclosure. The term "at least" in the context of the present invention means "equal or more" than the integer following the term. Thus, a vessel in the context of the present invention has one or more openings.
[0094] One or two openings, like the openings of a sample tube (one opening) or a syringe barrel (two openings) are preferred. If the vessel has two or more openings, they can be of same or different size. If there is more than one opening, one opening can be used for the gas inlet for a PECVD coating method according to the present invention, while the other openings are either capped or open.
[0095] A vessel according to the present invention can be a sample tube, e.g. for collecting or storing biological fluids like blood or urine, a syringe (or a part thereof, for example a syringe barrel) for storing or delivering a biologically active compound or composition, e.g. a medicament or pharmaceutical composition, a vial or ampoule for storing biological materials or biologically active compounds or compositions, a pipe, e.g. a catheter for transporting biological materials or biologically active compounds or compositions, or a cuvette for holding fluids, e.g. for holding biological materials or biologically active compounds or compositions. [0096] A vessel can be of any shape. One example of a vessel has a substantially cylindrical wall adjacent to at least one of its open ends. Generally, the interior wall of a vessel of this type is cylindrically shaped, like, e.g. in a sample tube or a syringe barrel. Sample tubes and syringes or their parts (for example syringe barrels), vials, and petri dishes, which commonly are generally cylindrical, are contemplated.
[0097] Some other non-limiting examples of contemplated vessels include well or non- well slides or plates, for example titer plates or microtiter plates. Still other non-limiting examples of contemplated vessels include pump contact surfaces in contact with the pumped material, including impeller contact surfaces, pump chamber contact surfaces and the like. Even other non-limiting examples of contemplated vessels include parts of an fluid containment, pumping, processing, filtering, and delivery system, such as an intravenous fluid delivery system, a blood processing system (such as a heart-lung machine or a blood component separator) a dialysis system, or the body or insulin contacting surfaces of an insulin delivery system, as several examples. Examples of such vessel parts are tubing, pump interior contact surfaces, drug or saline containing bags or bottles, adapters and tubing connectors for connecting parts of the system together, intravenous needles and needle assemblies, membranes and filters, etc. Other examples of vessels include measuring and delivery devices such as pipettes.
[0098] The invention has more general application to "contact surfaces" of medical devices and the like used or usable in contact with human or animal fluids or tissues, whether or not associated with a vessel. Some additional non-limiting examples of devices having contact surfaces are devices inserted in an orifice, through the skin, or otherwise within the body of a human or animal, such as thermometers, probes, guide wires, catheters, electrical leads, surgical drains, pacemakers, defibrillators, stents, contact lenses, artificial lens replacements, corneal replacements, and other devices placed in contact with the eye, orthopedic devices such as screws, plates, and rods, clothing, face masks, eye shields, and other equipment worn by medical personnel, surgical drapes, sheet or fabric material used to make the same, surgical instruments such as saws and saw blades, drills and drill bits, etc.
[0099] The invention further has application to any contact surfaces of devices used or usable in contact with pharmaceutical preparations or other materials, such as ampoules, vials, syringes, bottles, bags, or other containment vessels, stirring rods, impellers, stirring pellets, etc., also within the definition of "contact surfaces."
[00100] Some specific medical devices having fluid or tissue contacting surfaces that can be treated according to the present disclosure follow: an ACL/PCL Reconstruction System, an adapter, an adhesion barrier, an agar petri dish, an anesthesia unit, an anesthesia ventilator, an angiographic catheter, an ankle replacement, an aortic valve replacement, an apnea monitor, an applicator, an argon enhanced coagulation unit, an artificial facet replacement, an artificial heart, an artificial heart valve, an artificial organ, an artificial pacemaker, an artificial pancreas, an artificial urinary bladder, an aspirator, an atherectomy catheter, an auditory brainstem implant, an auto transfusion unit, a bag, a balloon catheter, a bare-metal stent, a beaker a bileaflet valve, a biliary stent, a bio implant, a bioceramic device, a bioresorbable stent, a biphasic cuirass ventilation, a blood culture device, a blood sample cassette, a blood sampling system, a bottle, a brain implant, a breast implant, a breast pump, a buccal sample cassette, a buttock augmentation, a caged-ball valve, a cannulated screw, a capillary blood collection device, a capsular contracture, a cardiac catheter, a cardiac defibrillator (external or internal), a cardiac output injectate kit and cable, a cardiac prosthesis, a cardiac shunt, a catheter, a cell lifter, a cell scraper, a cell spreader, a central cenous catheter, a centrifuge component, a cerebral shunt, a CHD stent, a chemical transfer pump, a chin augmentation, a chin sling, a cochlear implant, a collection and transport device, a colonic Stent, a compression pump, a connector, a container, a contraceptive implant, a cornea implant, a coronary stent, a Cotrel-Dubousset instrumentation, a cover glass, a cranio maxillofacial implant, a cryo/freezer box, a dehydrated culture media device, a deltec cozmo, a dental implant, a depression microscopic slide, a dewar flask, a DHS/DCS & angled blade plate, a diabetes accessory, a diaphragm pump, a diaphragmatic pacemaker, a direct testing and serology device, a disposable domes and kits, a double channel catheter, a double-lumen catheter, a drug-eluting stent, a duodenal stent, a dynamic compression plate, a dynamic hip screw, an elastomeric pump, an elbow replacement, an elbowed Catheter, an electrocardiograph (ECG), an electrode Catheter, an electroencephalograph (EEG), an electronic thermometer, an electro surgical unit, an endoscope, an enteral feeding pump, an environmental systems device, an esophageal stent, an external fixator, an external pacemaker, a female catheter, a fetal monitor, a film, a flat microscopic slide, a flow-restricted, oxygen-powered ventilation device, a fluid administration product, a fluid-filled catheter, a foley catheter, a forceps, a glaucoma valve, goggles, a Gouley catheter, a graft, a grommet, a Greuntzig balloon catheter, a Harrington rod, a heart valve, a heart-lung machine, a HeartMate left ventricular assist device, a hip prosthesis, a hip replacement, a hip resurfacing, a holder, a human-implantable RFID chip, a hypoxicator, a susceptibility device, an Implanon, an implant (medicine), an implantable cardioverter- defibrillator, an implantable defibrillator, an implantable device, an implantable gastric stimulation, an incubator, an in-dwelling catheter, an infusion set, an inhaler, an insulin pen, an insulin pump, an interlocking nail, an internal fixation, an intra-aortic balloon pump, an intramedullary rod, an intrathecal pump, an intravenous Catheter, an invasive blood pressure unit, an iron lung, an IV adapter, an IV catheter, an IV connector, an IV fluch syringe, an IV product, an IV site maintenance device, an IV stopcock, a joint replacement of the hand, a joint replacement, a keratometer, a Kirschner wire, a knee cartilage replacement therapy, a knee replacement, a lancet, a laparoscopic insufflator, large fragment implant, a lensometer, a liquid ventilator, a lytic bacteriophage, a medical grafting, a medical Pump, a medical ventilator, microbiology equipment and supplies, a microbiology testing device, a microchip implant (human), a microscopic Slide, a microtiter plate, a midline catheter, a mini dental implant, a mini Fragment Implant, a Minimplant, a molecular diagnostics device, a mycobacteria testing device, a nail, a wire, a pin, a needleless IV connector, a Nelaton urinary catheter, a Norplant
implantable birth control device, an O'Neil aspirating and irrigating needle, an O'Neil balloon infuser, an O'Neil intermittent urinary catheter, a contact lens, an orthopedic implant, an osseointegration implant, an oxinium replacement joint material, a pacemaker, a pacing Catheter, a pain management pump, a palatal obturator, a pancreatic Stent, a penile prosthesis, a penis enlargement device, a peripheral stent, a Peripherally Inserted Central Catheter (PICC), a peristaltic pump, a peritoneovenous shunt, a petri dish, a phonocardiograph, a phototherapy unit, a Pipette, a polyaxial screw, a port (medical), a portacaval shunt, a positive airway pressure device, a prepared media device, a pressure accessory or cable, a pressure transducer, a prostatic catheter, a prostatic stent, a pulmonary artery catheter, a pule oximeter, a radiant warmer, a radiation-therapy machine, a razor blade, a re-constructive prosthesis, a right-to-left shunt, a nerve stimulator, a safety supply, a sample collection container, a sample collection tube, a Sample Collection/Storage Device, a self-expandable metallic stent, a self-retaining catheter, a shaker flask, a shoulder replacement, a shunt (medical), a skin implant, a small fragment Implant, a snare catheter, Sphygmomanometer, a spinal cord stimulator, a spine surgery, a Stain, a Reagent, a static control supply, a stent graft, a stent, a sterility supply, a sterilizer, a stirrer, a subdermal implant, a surgical drill and saw, a surgical microscope, a suture, a swab, a Swan- Ganz catheter, a syringe driver, a temperature monitor, a Tenckhoff catheter, a Tiemann catheter, a tilting-disk valve, a tissue grinder, a toposcopic catheter, a transdermal implant, tubing, a tubing connector, a tubing link, a two-way catheter, ultrasonic nebulizer, an ultrasound sensor, an unicompartmental knee arthoplasty, an ureteral catheter, an ureteral stent, an urethral catheter, a urinary catheter, a urine sample cassette, a vascular ring connector, a vascular stent, a ventilator, ventricular assist device, vertebral fixation, a winged Catheter and X-ray diagnostic equipment..
[00101] A "hydrophobic layer" in the context of the present invention means that the coating lowers the wetting tension of a surface coated with the coating, compared to the corresponding uncoated surface. Hydrophobicity is thus a function of both the uncoated substrate and the coating. The same applies with appropriate alterations for other contexts wherein the term "hydrophobic" is used. The term "hydrophilic" means the opposite, i.e. that the wetting tension is increased compared to reference sample. The present hydrophobic layers are primarily defined by their hydrophobicity and the process conditions providing hydrophobicity, and optionally can have a composition according to the empirical composition or sum formula SiwOxCyHz, for example where w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9, optionally where w is 1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is from 6 to about 9. These values of w, x, y, and z are applicable to the empirical composition SiwOxCyHz throughout this specification. The values of w, x, y, and z used throughout this specification should be understood as ratios or an empirical formula (e.g. for a coating), rather than as a limit on the number or type of atoms in a molecule. For example, octamethylcyclotetrasiloxane, which has the molecular composition Si404C8H24, can be described by the following empirical formula, arrived at by dividing each of w, x, y, and z in the molecular formula by 4, the largest common factor: Sil01C2H6. The values of w, x, y, and z are also not limited to integers. For example, (acyclic) octamethyltrisiloxane, molecular composition S13O2C8H24, is reducible to SiiO0.67C2.67Hg.
[00102] "Wetting tension" is a specific measure for the hydrophobicity or hydrophilicity of a surface. An optional wetting tension measurement method in the context of the present invention is ASTM D 2578 or a modification of the method described in ASTM D 2578. This method uses standard wetting tension solutions (called dyne solutions) to determine the solution that comes nearest to wetting a plastic film surface for exactly two seconds. This is the film's wetting tension. The procedure utilized is varied herein from ASTM D 2578 in that the substrates are not flat plastic films, but are tubes made according to the Protocol for Forming PET Tube and (except for controls) coated according to the Protocol for Coating Tube Interior with
Hydrophobic Layer (see Example 9).
[00103] A "lubricity layer" according to the present invention is a coating which has a lower frictional resistance than the uncoated surface. In other words, it reduces the frictional resistance of the coated surface in comparison to a reference surface which is uncoated. The present lubricity layers are primarily defined by their lower frictional resistance than the uncoated surface and the process conditions providing lower frictional resistance than the uncoated surface, and optionally can have a composition according to the empirical composition SiwOxCyHz, as defined in this Definition Section. "Frictional resistance" can be static frictional resistance and/or kinetic frictional resistance. One of the optional embodiments of the present invention is a syringe part, e.g. a syringe barrel or plunger, coated with a lubricity layer. In this contemplated embodiment, the relevant static frictional resistance in the context of the present invention is the breakout force as defined herein, and the relevant kinetic frictional resistance in the context of the present invention is the plunger sliding force as defined herein. For example, the plunger sliding force as defined and determined herein is suitable to determine the presence or absence and the lubricity characteristics of a lubricity layer in the context of the present invention whenever the coating is applied to any syringe or syringe part, for example to the inner wall of a syringe barrel. The breakout force is of particular relevance for evaluation of the coating effect on a prefilled syringe, i.e. a syringe which is filled after coating and can be stored for some time, e.g. several months or even years, before the plunger is moved again (has to be "broken out").
[00104] The "plunger sliding force" in the context of the present invention is the force required to maintain movement of a plunger in a syringe barrel, e.g. during aspiration or dispense. It can advantageously be determined using the ISO 7886-1: 1993 test described herein and known in the art. A synonym for "plunger sliding force" often used in the art is "plunger force" or "pushing force". [00105] The "breakout force" in the context of the present invention is the initial force required to move the plunger in a syringe, for example in a prefilled syringe.
[00106] Both "plunger sliding force" and "breakout force" and methods for their measurement are described in more detail in subsequent parts of this description.
[00107] "Slidably" means that the plunger is permitted to slide in a syringe barrel.
[00108] An "antimicrobially effective" treatment means that the treated surface has greater antimicrobial activity, measured by a recognized test method, than a control represented by the same surface that has not been antimicrobially treated.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[00109] The present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which one or more embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are examples of the invention, which has the full scope indicated by the language of the claims. Like numbers refer to like elements throughout.
[00110] In the present method of making an antimicrobial medical device, a medical device or material or portion thereof is provided comprising a contact surface. A first treatment of SiOx, SiOxCy, or SiNxCy is applied to the contact surface. Then a second, antimicrobially effective, treatment is applied to the contact surface with its first treatment. The second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
[00111] The contact surface is defined in the definitions section above.
[00112] The first treatment of SiOx, SiOxCy, or SiNxCy is applied as described in US2010-
0298738, incorporated by reference above, parts of which are provided below, except that the description there of treating vessels refers to treatment of contact surfaces generally, exemplified by the contact surfaces of vessels. V. PECVD METHODS FOR TREATING CONTACT SURFACES
V.l Precursors for PECVD Coating
[00113] The precursor for the PECVD coating of the present invention is broadly defined as an organometallic precursor. An organometallic precursor is defined in this specification as comprehending compounds of metal elements from Group III and/or Group IV of the Periodic Table having organic residues, e.g. hydrocarbon, aminocarbon or oxycarbon residues.
Organometallic compounds as presently defined include any precursor having organic moieties bonded to silicon or other Group III/ IV metal atoms directly, or optionally bonded through oxygen or nitrogen atoms. The relevant elements of Group III of the Periodic Table are Boron, Aluminum, Gallium, Indium, Thallium, Scandium, Yttrium, and Lanthanum, Aluminum and Boron being preferred. The relevant elements of Group IV of the Periodic Table are Silicon, Germanium, Tin, Lead, Titanium, Zirconium, Hafnium, and Thorium, with Silicon and Tin being preferred. Other volatile organic compounds can also be contemplated. However, organosilicon compounds are preferred for performing present invention.
[00114] An organosilicon precursor is contemplated, where an "organosilicon precursor" is defined throughout this specification most broadly as a compound having at least one of the linkages:
-O-Si-C-H
or
-NH-Si-C-H
[00115] The first structure immediately above is a tetravalent silicon atom connected to an oxygen atom and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom). The second structure immediately above is a tetravalent silicon atom connected to an -NH- linkage and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom). Optionally, the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors. Also
contemplated as a precursor, though not within the two formulas immediately above, is an alkyl trimethoxysilane.
If an oxygen-containing precursor (e.g. a siloxane) is used, a representative predicted empirical composition resulting from PECVD under conditions forming a hydrophobic or lubricating coating would be SiwOxCyHz as defined in the Definition Section, while a representative predicted empirical composition resulting from PECVD under conditions forming a barrier coating would be SiOx, where x in this formula is from about 1.5 to about 2.9. If a nitrogen- containing precursor (e.g. a silazane) is used, the predicted composition would be Siw*Nx*Cy*Hz*, i.e. in SiwOxCyHz as specified in the Definition Section, O is replaced by N and the indices are adapted to the higher valency of N as compared to O (3 instead of 2). The latter adaptation will generally follow the ratio of w, x, y and z in a siloxane to the corresponding indices in its aza counterpart. In a particular aspect of the invention, Siw*Nx*Cy*Hz* in which w*, x*, y*, and z* are defined the same as w, x, y, and z for the siloxane counterparts, but for an optional deviation in the number of hydrogen atoms.
[00116] One type of precursor starting material having the above empirical formula is a linear siloxane, for example a material having the following formula:
Figure imgf000025_0001
in which each R is independently selected from alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others, and n is 1, 2, 3, 4, or greater, optionally two or greater. Several examples of contemplated linear siloxanes are
hexamethyldisiloxane (HMDSO),
octamethyltrisiloxane,
decamethyltetrasiloxane,
dodecamethylpentasiloxane, or combinations of two or more of these. The analogous silazanes in which -NH- is substituted for the oxygen atom in the above structure are also useful for making analogous coatings. Several examples of contemplated linear silazanes are octamethyltrisilazane,
decamethyltetrasilazane, or combinations of two or more of these.
[00117] V.C. Another type of precursor starting material is a monocyclic siloxane, for example a material having the following structural formula:
Figure imgf000026_0001
in which R is defined as for the linear structure and "a" is from 3 to about 10, or the analogous monocyclic silazanes. Several examples of contemplated hetero-substituted and unsubstituted monocyclic siloxanes and silazanes include
• l,3,5-trimethyl-l,3,5-tris(3,3,3-trifluoropropyl)methyl]cyclotrisiloxane
• 2,4,6, 8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane,
• pentamethylcyclopentasiloxane,
• pentavinylpentamethylcyclopentasiloxane,
• hexamethylcyclotrisiloxane,
• hexaphenylcyclotrisiloxane,
• octamethylcyclotetrasiloxane (OMCTS),
• octaphenylcyclotetrasiloxane,
• decamethylcyclopentasiloxane
• dodecamethylcyclohexasiloxane,
• methyl(3,3,3-trifluoropropl)cyclosiloxane,
• Cyclic organosilazanes are also contemplated, such as
• Octamethylcyclotetrasilazane,
• 1 ,3,5,7-tetravinyl- 1 ,3,5,7-tetramethylcyclotetrasilazane
hexamethylcyclotrisilazane,
• octamethylcyclotetrasilazane, • decamethylcyclopentasilazane,
• dodecamethylcyclohexasilazane, or
combinations of any two or more of these.
[00118] V.C. Another type of precursor starting material is a polycyclic siloxane, for example a material having one of the following structural formulas:
Figure imgf000027_0001
in which Y can be oxygen or nitrogen, E is silicon, and Z is a hydrogen atom or an organic substituent, for example alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others. When each Y is oxygen, the respective structures, from left to right, are a silatrane, a silquasilatrane, and a silproatrane. When Y is nitrogen, the respective structures are an azasilatrane, an azasilquasiatrane, and an azasilproatrane.
[00119] V.C. Another type of polycyclic siloxane precursor starting material is a
polysilsesquioxane, with the empirical formula RSiC .5 and the structural formula:
Figure imgf000027_0002
Tg cube in which each R is a hydrogen atom or an organic substituent, for example alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others. Two commercial materials of this sort are SST-eMOl poly(methylsilsesquioxane), in which each R is methyl, and SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which 90% of the R groups are methyl, 10% are hydrogen atoms. This material is available in a 10% solution in tetrahydrofuran, for example. Combinations of two or more of these are also contemplated. Other examples of a contemplated precursor are methylsilatrane, CAS No. 2288-13-3, in which each Y is oxygen and Z is methyl, methylazasilatrane, SST-eMOl poly(methylsilsesquioxane), in which each R optionally can be methyl, SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which 90% of the R groups are methyl and 10% are hydrogen atoms, or a combination of any two or more of these.
[00120] V.C. The analogous polysilsesquiazanes in which -NH- is substituted for the oxygen atom in the above structure are also useful for making analogous coatings. Examples of contemplated polysilsesquiazanes are a poly(methylsilsesquiazane), in which each R is methyl, and a poly(Methyl-Hydridosilsesquiazane, in which 90% of the R groups are methyl, 10% are hydrogen atoms. Combinations of two or more of these are also contemplated.
[00121] V.C. One particularly contemplated precursor for the lubricity layer according to the present invention is a monocyclic siloxane, for example is octamethylcyclotetrasiloxane.
[00122] One particularly contemplated precursor for the hydrophobic layer according to the present invention is a monocyclic siloxane, for example is octamethylcyclotetrasiloxane.
[00123] One particularly contemplated precursor for the barrier coating according to the present invention is a linear siloxane, for example is HMDSO.
[00124] V.C. In any of the coating methods according to the present invention, the applying step optionally can be carried out by vaporizing the precursor and providing it in the vicinity of the substrate. E.g., OMCTS is usually vaporized by heating it to about 50°C before applying it to the PECVD apparatus.
V.2 General PECVD Method
[00125] In the context of the present invention, the following PECVD method is generally applied, which contains the following steps:
(a) providing a gaseous reactant comprising a precursor as defined herein, optionally an organosilicon precursor, and optionally 02 in the vicinity of the substrate contact surface; and
(b) generating a plasma from the gaseous reactant, thus forming a coating on the substrate contact surface by plasma enhanced chemical vapor deposition (PECVD).
[00126] In the method, the coating characteristics are advantageously set by one or more of the following conditions: the plasma properties, the pressure under which the plasma is applied, the power applied to generate the plasma, the presence and relative amount of 02 in the gaseous reactant, the plasma volume, and the organosilicon precursor. Optionally, the coating
characteristics are set by the presence and relative amount of 02 in the gaseous reactant and/or the power applied to generate the plasma.
[00127] In all embodiments of the present invention, the plasma is in an optional aspect a non- hollow-cathode plasma.
In a further preferred aspect, the plasma is generated at reduced pressure (as compared to the ambient or atmospheric pressure). Optionally, the reduced pressure is less than 300 mTorr, optionally less than 200 mTorr, even optionally less than 100 mTorr.
[00128] The PECVD optionally is performed by energizing the gaseous reactant containing the precursor with electrodes powered at a frequency at microwave or radio frequency, and optionally at a radio frequency. The radio frequency preferred to perform an embodiment of the invention will also be addressed as "RF frequency". A typical radio frequency range for performing the present invention is a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz. A frequency of 13.56 MHz is most preferred, this being a government sanctioned frequency for conducting PECVD work.
[00129] There are several advantages for using a RF power source versus a microwave source: Since RF operates a lower power, there is less heating of the substrate/vessel. Because the focus of the present invention is putting a plasma coating on plastic substrates, lower processing temperature are desired to prevent melting/distortion of the substrate. To prevent substrate overheating when using microwave PECVD, the microwave PECVD is applied in short bursts, by pulsing the power. The power pulsing extends the cycle time for the coating, which is undesired in the present invention. The higher frequency microwave can also cause offgassing of volatile substances like residual water, oligomers and other materials in the plastic substrate. This offgassing can interfere with the PECVD coating. A major concern with using microwave for PECVD is delamination of the coating from the substrate. Delamination occurs because the microwaves change the contact surface of the substrate prior to depositing the coating layer. To mitigate the possibility of delamination, interface coating layers have been developed for microwave PECVD to achieve good bonding between the coating and the substrate. No such interface coating layer is needed with RF PECVD as there is no risk of delamination. Finally, the lubricity layer and hydrophobic layer according to the present invention are advantageously applied using lower power. RF power operates at lower power and provides more control over the PECVD process than microwave power. Nonetheless, microwave power, though less preferred, is usable under suitable process conditions.
[00130] Furthermore, for all PECVD methods described herein, there is a specific correlation between the power (in Watts) used to generate the plasma and the volume of the lumen wherein the plasma is generated. Typically, the lumen is the lumen of a vessel coated according to the present invention. The RF power should scale with the volume of the vessel if the same electrode system is employed. Once the composition of a gaseous reactant, for example the ratio of the precursor to 02, and all other parameters of the PECVD coating method but the power have been set, they will typically not change when the geometry of a vessel is maintained and only its volume is varied. In this case, the power will be directly proportional to the volume. Thus, starting from the power to volume ratios provided by present description, the power which has to be applied in order to achieve the same or a similar coating in a vessel of same geometry, but different size, can easily be found. The influence of the vessel geometry on the power to be applied is illustrated by the results of the Examples for tubes in comparison to the Examples for syringe barrels.
[00131] For any coating of the present invention, the plasma is generated with electrodes powered with sufficient power to form a coating on the substrate contact surface. For a lubricity layer or hydrophobic layer, in the method according to an embodiment of the invention the plasma is optionally generated
(i) with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, for example of 8 W; and/or (ii) wherein the ratio of the electrode power to the plasma volume is less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. For a barrier coating or SiOx coating, the plasma is optionally generated (i) with electrodes supplied with an electric power of from 8 to 500 W, optionally from 20 to 400 W, optionally from 35 to 350 W, even optionally from 44 to 300 W, optionally from 44 to 70 W; and/or
(ii) the ratio of the electrode power to the plasma volume is equal or more than 5 W/ml, optionally is from 6 W/ml to 150 W/ml, optionally is from 7 W/ml to 100 W/ml, optionally from 7 W/ml to 20 W/ml.
[00132] The vessel geometry can also influence the choice of the gas inlet used for the PECVD coating. In a particular aspect, a syringe can be coated with an open tube inlet, and a tube can be coated with a gas inlet having small holes which is extended into the tube.
[00133] The power (in Watts) used for PECVD also has an influence on the coating properties. Typically, an increase of the power will increase the barrier properties of the coating, and a decrease of the power will increase the lubricity and hydrophobicity of the coating. E.g., for a coating on the inner wall of syringe barrel having a volume of about 3 ml, a power of less than 30 W will lead to a coating which is predominantly a barrier coating, while a power of more than 30 W will lead to a coating which is predominantly a lubricity layer (see Examples).
[00134] A further parameter determining the coating properties is the ratio of 02 (or another oxidizing agent) to the precursor (e.g. organosilicon precursor) in the gaseous reactant used for generating the plasma. Typically, an increase of the 02 ratio in the gaseous reactant will increase the barrier properties of the coating, and a decrease of the 02 ratio will increase the lubricity and hydrophobicity of the coating.
[00135] If a lubricity layer is desired, then 02 is optionally present in a volume-volume ratio to the gaseous reactant of from 0: 1 to 5: 1, optionally from 0: 1 to 1: 1, even optionally from 0: 1 to 0.5: 1 or even from 0: 1 to 0.1: 1. Most advantageously, essentially no oxygen is present in the gaseous reactant. Thus, the gaseous reactant should comprise less than 1 vol 02, for example less than 0.5 vol 02, and optionally is 02-free.The same applies to a hydrophobic layer.
[00136] If, on the other hand, a barrier or SiOx coating is desired, then the 02 is optionally present in a volume : volume ratio to the gaseous reactant of from 1 : 1 to 100 : 1 in relation to the silicon containing precursor, optionally in a ratio of from 5 : 1 to 30 : 1, optionally in a ratio of from 10 : 1 to 20 : 1, even optionally in a ratio of 15 : 1.
V.A. PECVD to apply SiOx barrier coating, using plasma that is substantially free of hollow cathode plasma
[00137] V.A. A specific embodiment is a method of applying a barrier coating of SiOx, defined in this specification (unless otherwise specified in a particular instance) as a coating containing silicon, oxygen, and optionally other elements, in which x, the ratio of oxygen to silicon atoms, is from about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2. These alternative definitions of x apply to any use of the term SiOx in this specification. The barrier coating is applied to a contact surface, for example a sample collection tube, a syringe barrel, or another type of vessel. The method includes several steps.
[00138] V.A. A vessel wall is provided, as is a reaction mixture comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas.
[00139] V.A. Plasma is formed in the reaction mixture that is substantially free of hollow cathode plasma. The vessel wall is contacted with the reaction mixture, and the coating of SiOx is deposited on at least a portion of the vessel wall.
[00140] V.A. In certain embodiments, the generation of a uniform plasma throughout the portion of the vessel to be coated is contemplated, as it has been found in certain instances to generate an SiOx coating providing a better barrier against oxygen. Uniform plasma means regular plasma that does not include a substantial amount of hollow cathode plasma (which has a higher emission intensity than regular plasma and is manifested as a localized area of higher intensity interrupting the more uniform intensity of the regular plasma).
[00141] V.A. The hollow cathode effect is generated by a pair of conductive contact surfaces opposing each other with the same negative potential with respect to a common anode. If the spacing is made (depending on the pressure and gas type) such that the space charge sheaths overlap, electrons start to oscillate between the reflecting potentials of the opposite wall sheaths leading to multiple collisions as the electrons are accelerated by the potential gradient across the sheath region. The electrons are confined in the space charge sheath overlap which results in very high ionization and high ion density plasmas. This phenomenon is described as the hollow cathode effect. Those skilled in the art are able to vary the processing conditions, such as the power level and the feed rates or pressure of the gases, to form uniform plasma throughout or to form plasma including various degrees of hollow cathode plasma.
[00142] V.A. In an alternate method, using for example the apparatus of FIG. 12 previously described, microwave energy can be used to generate the plasma in a PECVD process. The processing conditions can be different, however, as microwave energy applied to a thermoplastic vessel will excite (vibrate) water molecules. Since there is a small amount of water in all plastic materials, the microwaves will heat the plastic. As the plastic heats, the large driving force created by the vacuum inside of the device relative to atmospheric pressure outside the device will pull free or easily desorb materials to the interior contact surface 88 where they will either become volatile or will be weakly bound to the contact surface. The weakly bound materials will then create an interface that can hinder subsequent coatings (deposited from the plasma) from adhering to the plastic interior contact surface 88 of the device.
[00143] V.A. As one way to negate this coating hindering effect, a coating can be deposited at very low power (in the example above 5 to 20 Watts at 2.45 GHz) creating a cap onto which subsequent coatings can adhere. This results in a two-step coating process (and two coating layers). In the example above, the initial gas flows (for the capping layer) can be changed to 2 seem ("standard cubic centimeters per minute") HMDSO and 20 seem oxygen with a process power of 5 to 20 Watts for approximately 2-10 seconds. Then the gases can be adjusted to the flows in the example above and the power level increased to 20-50 Watts so that an SiOx coating, in which x in this formula is from about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6, alternatively about 2, can be deposited. Note that the capping layer might provide little to no functionality in certain embodiments, except to stop materials from migrating to the vessel interior contact surface 88 during the higher power SiOx coating deposition. Note also that migration of easily desorbed materials in the device walls typically is not an issue at lower frequencies such as most of the RF range, since the lower frequencies do not excite (vibrate) molecular species.
[00144] V.A. As another way to negate the coating hindering effect described above, the vessel 80 can be dried to remove embedded water before applying microwave energy. Desiccation or drying of the vessel 80 can be accomplished, for example, by thermally heating the vessel 80, as by using an electric heater or forced air heating. Desiccation or drying of the vessel 80 also can be accomplished by exposing the interior of the vessel 80, or gas contacting the interior of the vessel 80, to a desiccant. Other expedients for drying the vessel, such as vacuum drying, can also be used. These expedients can be carried out in one or more of the stations or devices illustrated or by a separate station or device.
[00145] V.A. Additionally, the coating hindering effect described above can be addressed by selection or processing of the resin from which the vessels 80 are molded to minimize the water content of the resin.
V.B. PECVD Coating Restricted Opening of Vessel (Syringe Capillary)
[00146] V.B. FIGS. 26 and 27 show a method and apparatus generally indicated at 290 for coating an inner contact surface 292 of a restricted opening 294 of a generally tubular vessel 250 to be processed, for example the restricted front opening 294 of a syringe barrel 250, by PECVD. The previously described process is modified by connecting the restricted opening 294 to a processing vessel 296 and optionally making certain other modifications.
[00147] V.B. The generally tubular vessel 250 to be processed includes an outer contact surface 298, an inner or interior contact surface 254 defining a lumen 300, a larger opening 302 having an inner diameter, and a restricted opening 294 that is defined by an inner contact surface 292 and has an inner diameter smaller than the inner diameter of the larger opening 302.
[00148] V.B. The processing vessel 296 has a lumen 304 and a processing vessel opening 306, which optionally is the only opening, although in other embodiments a second opening can be provided that optionally is closed off during processing. The processing vessel opening 306 is connected with the restricted opening 294 of the vessel 250 to be processed to establish communication between the lumen 300 of the vessel 250 to be processed and the processing vessel lumen via the restricted opening 294.
[00149] V.B. At least a partial vacuum is drawn within the lumen 300 of the vessel 250 to be processed and lumen 304 of the processing vessel 296. A PECVD reactant is flowed from the gas source 144 (see FIG. 7) through the first opening 302, then through the lumen 300 of the vessel 250 to be processed, then through the restricted opening 294, then into the lumen 304 of the processing vessel 296.
[00150] V.B. The PECVD reactant can be introduced through the larger opening 302 of the vessel 250 by providing a generally tubular inner electrode 308 having an interior passage 310, a proximal end 312, a distal end 314, and a distal opening 316, in an alternative embodiment multiple distal openings can be provided adjacent to the distal end 314 and communicating with the interior passage 310. The distal end of the electrode 308 can be placed adjacent to or into the larger opening 302 of the vessel 250 to be processed. A reactant gas can be fed through the distal opening 316 of the electrode 308 into the lumen 300 of the vessel 250 to be processed. The reactant will flow through the restricted opening 294, then into the lumen 304, to the extent the PECVD reactant is provided at a higher pressure than the vacuum initially drawn before introducing the PECVD reactant.
[00151] V.B. Plasma 318 is generated adjacent to the restricted opening 294 under conditions effective to deposit a coating of a PECVD reaction product on the inner contact surface 292 of the restricted opening 294. In the embodiment shown in FIG. 26, the plasma is generated by feeding RF energy to the generally U-shaped outer electrode 160 and grounding the inner electrode 308. The feed and ground connections to the electrodes could also be reversed, though this reversal can introduce complexity if the vessel 250 to be processed, and thus also the inner electrode 308, are moving through the U-shaped outer electrode while the plasma is being generated.
[00152] V.B. The plasma 318 generated in the vessel 250 during at least a portion of processing can include hollow cathode plasma generated inside the restricted opening 294 and/or the processing vessel lumen 304. The generation of hollow cathode plasma 318 can contribute to the ability to successfully apply a barrier coating at the restricted opening 294, although the invention is not limited according to the accuracy or applicability of this theory of operation. Thus, in one contemplated mode of operation, the processing can be carried out partially under conditions generating a uniform plasma throughout the vessel 250 and the gas inlet, and partially under conditions generating a hollow cathode plasma, for example adjacent to the restricted opening 294. [00153] V.B. The process is desirably operated under such conditions, as explained here and shown in the drawings, that the plasma 318 extends substantially throughout the syringe lumen 300 and the restricted opening 294. The plasma 318 also desirably extends substantially throughout the syringe lumen 300, the restricted opening 294, and the lumen 304 of the processing vessel 296. This assumes that a uniform coating of the interior 254 of the vessel 250 is desired. In other embodiments non-uniform plasma can be desired.
[00154] V.B. It is generally desirable that the plasma 318 have a substantially uniform color throughout the syringe lumen 300 and the restricted opening 294 during processing, and optionally a substantially uniform color substantially throughout the syringe lumen 300, the restricted opening 294, and the lumen 304 of the processing vessel 296. The plasma desirably is substantially stable throughout the syringe lumen 300 and the restricted opening 294, and optionally also throughout the lumen 304 of the processing vessel 296.
[00155] V.B. The order of steps in this method is not contemplated to be critical.
[00156] V.B. In the embodiment of FIGS. 26 and 27, the restricted opening 294 has a first fitting 332 and the processing vessel opening 306 has a second fitting 334 adapted to seat to the first fitting 332 to establish communication between the lumen 304 of the processing vessel 296 and the lumen 300 of the vessel 250 to be processed.
[00157] V.B. In the embodiment of FIGS. 26 and 27, the first and second fittings are male and female Luer lock fittings 332 and 334, respectively integral with the structure defining the restricted opening 294 and the processing vessel opening 306. One of the fittings, in this case the male Luer lock fitting 332, comprises a locking collar 336 with a threaded inner contact surface and defining an axially facing, generally annular first abutment 338 and the other fitting 334 comprises an axially facing, generally annular second abutment 340 facing the first abutment 338 when the fittings 332 and 334 are engaged.
[00158] V.B. In the illustrated embodiment a seal, for example an O-ring 342 can be positioned between the first and second fittings 332 and 334. For example, an annular seal can be engaged between the first and second abutments 338 and 340. The female Luer fitting 334 also includes dogs 344 that engage the threaded inner contact surface of the locking collar 336 to capture the O-ring 342 between the first and second fittings 332 and 334. Optionally, the communication established between the lumen 300 of the vessel 250 to be processed and the lumen 304 of the processing vessel 296 via the restricted opening 294 is at least substantially leak proof.
[00159] V.B. As a further option, either or both of the Luer lock fittings 332 and 334 can be made of electrically conductive material, for example stainless steel. This construction material forming or adjacent to the restricted opening 294 might contribute to formation of the plasma in the restricted opening 294.
[00160] V.B. The desirable volume of the lumen 304 of the processing vessel 296 is contemplated to be a trade-off between a small volume that will not divert much of the reactant flow away from the product contact surfaces desired to be coated and a large volume that will support a generous reactant gas flow rate through the restricted opening 294 before filling the lumen 304 sufficiently to reduce that flow rate to a less desirable value (by reducing the pressure difference across the restricted opening 294). The contemplated volume of the lumen 304, in an embodiment, is less than three times the volume of the lumen 300 of the vessel 250 to be processed, or less than two times the volume of the lumen 300 of the vessel 250 to be processed, or less than the volume of the lumen 300 of the vessel 250 to be processed, or less than 50% of the volume of the lumen 300 of the vessel 250 to be processed, or less than 25% of the volume of the lumen 300 of the vessel 250 to be processed. Other effective relationships of the volumes of the respective lumens are also contemplated.
[00161] V.B. The inventors have found that the uniformity of coating can be improved in certain embodiments by repositioning the distal end of the electrode 308 relative to the vessel 250 so it does not penetrate as far into the lumen 300 of the vessel 250 as the position of the inner electrode shown in previous Figures. For example, although in certain embodiments the distal opening 316 can be positioned adjacent to the restricted opening 294, in other
embodiments the distal opening 316 can be positioned less than 7/8 the distance, optionally less than ¾ the distance, optionally less than half the distance to the restricted opening 294 from the larger opening 302 of the vessel to be processed while feeding the reactant gas. Or, the distal opening 316 can be positioned less than 40%, less than 30%, less than 20%, less than 15%, less than 10%, less than 8%, less than 6%, less than 4%, less than 2%, or less than 1% of the distance to the restricted opening 294 from the larger opening of the vessel to be processed while feeding the reactant gas. [00162] V.B. Or, the distal end of the electrode 308 can be positioned either slightly inside or outside or flush with the larger opening 302 of the vessel 250 to be processed while
communicating with, and feeding the reactant gas to, the interior of the vessel 250. The positioning of the distal opening 316 relative to the vessel 250 to be processed can be optimized for particular dimensions and other conditions of treatment by testing it at various positions. One particular position of the electrode 308 contemplated for treating syringe barrels 250 is with the distal end 314 penetrating about a quarter inch (about 6 mm) into the vessel lumen 300 above the larger opening 302.
[00163] V.B. The inventors presently contemplate that it is advantageous to place at least the distal end 314 of the electrode 308 within the vessel 250 so it will function suitably as an electrode, though that is not necessarily a requirement. Surprisingly, the plasma 318 generated in the vessel 250 can be made more uniform, extending through the restricted opening 294 into the processing vessel lumen 304, with less penetration of the electrode 308 into the lumen 300 than has previously been employed. With other arrangements, such as processing a closed-ended vessel, the distal end 314 of the electrode 308 commonly is placed closer to the closed end of the vessel than to its entrance.
[00164] V.B. Or, the distal end 314 of the electrode 308 can be positioned at the restricted opening 294 or beyond the restricted opening 294, for example within the processing vessel lumen 304, as illustrated for example in FIG. 33. Various expedients can optionally be provided, such as shaping the processing vessel 296 to improve the gas flow through the restricted opening 294.
[00165] V.B. As another alternative, illustrated in FIGS. 34-35, the composite inner electrode and gas supply tube 398 can have distal gas supply openings such as 400, optionally located near the larger opening 302, and an extension electrode 402 extending distal of the distal gas supply openings 400, optionally extending to a distal end adjacent to the restricted opening 294, and optionally further extending into the processing vessel 324. This construction is contemplated to facilitate formation of plasma within the inner contact surface 292 adjacent to the restricted opening 294.
[00166] V.B. In yet another contemplated embodiment, the inner electrode 308, as in FIG. 26, can be moved during processing, for example, at first extending into the processing vessel lumen 304, then being withdrawn progressively proximally as the process proceeds. This expedient is particularly contemplated if the vessel 250, under the selected processing conditions, is long, and movement of the inner electrode facilitates more uniform treatment of the interior contact surface 254. Using this expedient, the processing conditions, such as the gas feed rate, the vacuum draw rate, the electrical energy applied to the outer electrode 160, the rate of withdrawing the inner electrode 308, or other factors can be varied as the process proceeds, customizing the process to different parts of a vessel to be treated.
[00167] V.B. Conveniently, as in the other processes described in this specification, the larger opening of the generally tubular vessel 250 to be processed can be placed on a vessel support 320, as by seating the larger opening 302 of the vessel 250 to be processed on a port 322 of the vessel support 320. Then the inner electrode 308 can be positioned within the vessel 250 seated on the vessel support 320 before drawing at least a partial vacuum within the lumen 300 of the vessel 250 to be processed.
[00168] V.B. In an alternative embodiment, illustrated in FIG. 28, the processing vessel 324 can be provided in the form of a conduit having a first opening 306 secured to the vessel 250 to be processed, as shown in FIG. 26, and a second opening 328 communicating with a vacuum port 330 in the vessel support 320. In this embodiment, the PECVD process gases can flow into the vessel 250, then via the restricted opening 294 into the processing vessel 324, then return via the vacuum port 330. Optionally, the vessel 250 can be evacuated through both openings 294 and 302 before applying the PECVD reactants.
[00169] V.B. Or, an uncapped syringe barrel 250, as shown in FIG. 22, can be provided with an interior coating of SiOx, in which x in this formula is from about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6, alternatively about 2, barrier or other type of PECVD coating by introducing the reactants from the source 144 through the opening at the back end 256 of the barrel 250 and drawing a vacuum using the vacuum source 98 drawing through the opening at the front end 260 of the barrel. For example, the vacuum source 98 can be connected through a second fitting 266 seated on the front end 260 of the syringe barrel 250. Using this expedient, the reactants can flow through the barrel 250 in a single direction (upward as shown in FIG. 22, though the orientation is not critical), and there is no need to convey the reactants through a probe that separates the fed gas from the exhausted gas within the syringe barrel 250. The front and back ends 260 and 256 of the syringe barrel 250 can also be reversed relative to the coating apparatus, in an alternative arrangement. The probe 108 can act simply as an electrode, and can either be tubular or a solid rod in this embodiment. As before, the separation between the interior contact surface 254 and the probe 108 can be uniform over at least most of the length of the syringe barrel 250.
[00170] V.B. FIG. 37 is a view similar to FIG. 22 showing another embodiment in which the fitting 266 is independent of and not attached to the plate electrodes 414 and 416. The fitting 266 can have a Luer lock fitting adapted to be secured to the corresponding fitting of the syringe barrel 250. This embodiment allows the vacuum conduit 418 to pass over the electrode 416 while the vessel holder 420 and attached vessel 250 move between the electrodes 414 and 416 during a coating step.
[00171] V.B. FIG. 38 is a view similar to FIG. 22 showing still another embodiment in which the front end 260 of the syringe barrel 250 is open and the syringe barrel 250 is enclosed by a vacuum chamber 422 seated on the vessel holder 424. In this embodiment the pressures PI within the syringe barrel 250 and within the vacuum chamber 422 are approximately identical, and the vacuum in the vacuum chamber 422 optionally is drawn through the front end 260 of the syringe barrel 250. When the process gases flow into the syringe barrel 250, they flow through the front end 260 of the syringe barrel 250 until a steady composition is provided within the syringe barrel 250, at which time the electrode 160 is energized to form the coating. It is contemplated that due to the larger volume of the vacuum chamber 422 relative to the syringe barrel 250, and the location of the counter electrode 426 within the syringe barrel 250, the process gases passing through the front end 260 will not form substantial deposits on the walls of the vacuum chamber 422.
[00172] V.B. FIG. 39 is a view similar to FIG. 22 showing yet another embodiment in which the back flange of the syringe barrel 250 is clamped between a vessel holder 428 and an electrode assembly 430 to which a cylindrical electrode or pair of plate electrodes indicated as 160 and a vacuum source 98 are secured. The volume generally indicated as 432 enclosed outside the syringe barrel 250 is relatively small in this embodiment to minimize the pumping needed to evacuate the volume 432 and the interior of the syringe barrel 250 to operate the PECVD process. [00173] V.B. FIG. 40 is a view similar to FIG. 22 and FIG. 41 is a plan view showing even another embodiment as an alternative to FIG. 38 in which the ratio of pressures P1/P2 is maintained at a desired level by providing a pressure proportioning valve 434. It is contemplated that PI can be a lower vacuum, i.e. a higher pressure than P2 during a PECVD process so the waste process gases and by-products will pass through the front end 260 of the syringe barrel 250 and be exhausted. Also, the provision of a separate vacuum chamber conduit 436 to serve the vacuum chamber 422 allows the use of a separate vacuum pump to evacuate the greater enclosed volume 432 more quickly.
[00174] V.B. FIG. 41 is a plan view of the embodiment of FIG. 40, also showing the electrode 160 removed from FIG. 40.
V.C. Method of Applying a Lubricity Layer
[00175] V.C. Another embodiment is a method of applying a lubricity layer derived from an organosilicon precursor. A "lubricity layer" or any similar term is generally defined as a coating that reduces the frictional resistance of the coated contact surface, relative to the uncoated contact surface. If the coated object is a syringe (or syringe part, e.g. syringe barrel) or any other item generally containing a plunger or movable part in sliding contact with the coated contact surface, the frictional resistance has two main aspects - breakout force and plunger sliding force.
[00176] The plunger sliding force test is a specialized test of the coefficient of sliding friction of the plunger within a syringe, accounting for the fact that the normal force associated with a coefficient of sliding friction as usually measured on a flat contact surface is addressed by standardizing the fit between the plunger or other sliding element and the tube or other vessel within which it slides. The parallel force associated with a coefficient of sliding friction as usually measured is comparable to the plunger sliding force measured as described in this specification. Plunger sliding force can be measured, for example, as provided in the ISO 7886- 1: 1993 test.
[00177] The plunger sliding force test can also be adapted to measure other types of frictional resistance, for example the friction retaining a stopper within a tube, by suitable variations on the apparatus and procedure. In one embodiment, the plunger can be replaced by a closure and the withdrawing force to remove or insert the closure can be measured as the counterpart of plunger sliding force.
[00178] Also or instead of the plunger sliding force, the breakout force can be measured. The breakout force is the force required to start a stationary plunger moving within a syringe barrel, or the comparable force required to unseat a seated, stationary closure and begin its movement. The breakout force is measured by applying a force to the plunger that starts at zero or a low value and increases until the plunger begins moving. The breakout force tends to increase with storage of a syringe, after the prefilled syringe plunger has pushed away the intervening lubricant or adhered to the barrel due to decomposition of the lubricant between the plunger and the barrel. The breakout force is the force needed to overcome "sticktion," an industry term for the adhesion between the plunger and barrel that needs to be overcome to break out the plunger and allow it to begin moving.
[00179] V.C. Some utilities of coating a vessel in whole or in part with a lubricity layer, such as selectively at contact surfaces contacted in sliding relation to other parts, is to ease the insertion or removal of a stopper or passage of a sliding element such as a piston in a syringe or a stopper in a sample tube. The vessel can be made of glass or a polymer material such as polyester, for example polyethylene terephthalate (PET), a cyclic olefin copolymer (COC), an olefin such as polypropylene, or other materials. Applying a lubricity layer by PECVD can avoid or reduce the need to coat the vessel wall or closure with a sprayed, dipped, or otherwise applied organosilicon or other lubricant that commonly is applied in a far larger quantity than would be deposited by a PECVD process.
[00180] V.C. In any of the above embodiments V.C, a plasma, optionally a non-hollow- cathode plasma, optionally can be formed in the vicinity of the substrate
[00181] V.C. In any of embodiments V.C, the precursor optionally can be provided in the substantial absence of oxygen. V.C. In any of embodiments V.C, the precursor optionally can be provided in the substantial absence of a carrier gas. V.C. In any of embodiments V.C, in which the precursor optionally can be provided in the substantial absence of nitrogen. V.C. In any of embodiments V.C, in which the precursor optionally can be provided at less than 1 Torr absolute pressure. [00182] V.C. In any of embodiments V.C., the precursor optionally can be provided to the vicinity of a plasma emission.
[00183] V.C. In any of embodiments V.C, the coating optionally can be applied to the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm, or 10-200 nm, or 20 to 100 nm thick. The thickness of this and other coatings can be measured, for example, by transmission electron microscopy (TEM).
[00184] V.C. The TEM can be carried out, for example, as follows. Samples can be prepared for Focused Ion Beam (FIB) cross-sectioning in two ways. Either the samples can be first coated with a thin layer of carbon (50-100nm thick) and then coated with a sputtered layer of platinum (50-100nm thick) using a K575X Emitech coating system, or the samples can be coated directly with the protective sputtered Pt layer. The coated samples can be placed in an FEI FIB200 FIB system. An additional layer of platinum can be FIB-deposited by injection of an oregano- metallic gas while rastering the 30kV gallium ion beam over the area of interest. The area of interest for each sample can be chosen to be a location half way down the length of the syringe barrel. Thin cross sections measuring approximately 15μιη ("micrometers") long, 2μιη wide and 15μιη deep can be extracted from the die contact surface using a proprietary in-situ FIB lift-out technique. The cross sections can be attached to a 200 mesh copper TEM grid using FIB- deposited platinum. One or two windows in each section, measuring ~ 8μιη wide, can be thinned to electron transparency using the gallium ion beam of the FEI FIB.
[00185] V.C. Cross-sectional image analysis of the prepared samples can be performed utilizing either a Transmission Electron Microscope (TEM), or a Scanning Transmission
Electron Microscope (STEM), or both. All imaging data can be recorded digitally. For STEM imaging, the grid with the thinned foils can be transferred to a Hitachi HD2300 dedicated STEM. Scanning transmitted electron images can be acquired at appropriate magnifications in atomic number contrast mode (ZC) and transmitted electron mode (TE). The following instrument settings can be used. Scanning Transmission Electron
1. Instrument
Microscope
Manufacturer/Model Hitachi HD2300
Accelerating Voltage 200kV
Objective Aperture #2
Condenser Lens 1 Setting 1.672
Condenser Lens 2 Setting 1.747
Approximate Objective Lens Setting 5.86
ZC Mode Projector Lens 1.149
TE Mode Projector Lens 0.7
Image Acquisition
Pixel Resolution 1280x960
Acquisition Time 20sec.(x4)
[00186] V.C. For TEM analysis the sample grids can be transferred to a Hitachi HF2000 transmission electron microscope. Transmitted electron images can be acquired at appropriate magnifications. The relevant instrument settings used during image acquisition can be those given below.
Transmission Electron
Instrument
Microscope
Manufacturer/Model Hitachi HF2000
Accelerating Voltage 200 kV
Condenser Lens 1 0.78
Condenser Lens 2 0
Objective Lens 6.34
Condenser Lens Aperture #1
Objective Lens Aperture for #3
imaging
Selective Area Aperture for SAD N/A
[00187] V.C. In any of embodiments V.C, the substrate can comprise glass or a polymer, for example a polycarbonate polymer, an olefin polymer, a cyclic olefin copolymer, a polypropylene polymer, a polyester polymer, a polyethylene terephthalate polymer or a combination of any two or more of these. [00188] V.C. In any of embodiments V.C., the PECVD optionally can be performed by energizing the gaseous reactant containing the precursor with electrodes powered at a RF frequency as defined above, for example a frequency from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
[00189] V.C. In any of embodiments V.C, the plasma can be generated by energizing the gaseous reactant comprising the precursor with electrodes supplied with electric power sufficient to form a lubricity layer. Optionally, the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W. The ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. These power levels are suitable for applying lubricity coatings to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
[00190] V.C. One contemplated product optionally can be a syringe having a barrel treated by the method of any one or more of embodiments V.C.
V.D. Liquid-applied Coatings
[00191] V.D. Another example of a suitable barrier or other type of coating, usable in conjunction with PECVD-applied coatings or other PECVD treatment as disclosed here, can be a liquid barrier, lubricant, contact surface energy tailoring, or other type of coating 90 applied to the interior contact surface of a vessel, either directly or with one or more intervening PECVD- applied coatings described in this specification, for example SiOx, a lubricity layer characterized as defined in the Definition Section, or both.
[00192] V.D. Suitable liquid barriers or other types of coatings 90 also optionally can be applied, for example, by applying a liquid monomer or other polymerizable or curable material to the interior contact surface of the vessel 80 and curing, polymerizing, or crosslinking the liquid monomer to form a solid polymer. Suitable liquid barrier or other types of coatings 90 can also be provided by applying a solvent-dispersed polymer to the contact surface 88 and removing the solvent.
[00193] V.D. Either of the above methods can include as a step forming a coating 90 on the interior 88 of a vessel 80 via the vessel port 92 at a processing station or device 28. One example is applying a liquid coating, for example of a curable monomer, prepolymer, or polymer dispersion, to the interior contact surface 88 of a vessel 80 and curing it to form a film that physically isolates the contents of the vessel 80 from its interior contact surface 88. The prior art describes polymer coating technology as suitable for coating plastic blood collection tubes. For example, the acrylic and polyvinylidene chloride (PVdC) coating materials and coating methods described in US Patent 6,165,566, which is hereby incorporated by reference, optionally can be used.
[00194] V.D. Either of the above methods can also or include as a step forming a coating on the exterior outer wall of a vessel 80. The coating optionally can be a barrier coating, optionally an oxygen barrier coating, or optionally a water barrier coating. One example of a suitable coating is polyvinylidene chloride, which functions both as a water barrier and an oxygen barrier. Optionally, the barrier coating can be applied as a water-based coating. The coating optionally can be applied by dipping the vessel in it, spraying it on the vessel, or other expedients. A vessel having an exterior barrier coating as described above is also contemplated.
VII. PECVD TREATED VESSELS
[00195] VII. Vessels are contemplated having a barrier coating 90 (shown in FIG. 2, for example), which can be an SiOx coating applied to a thickness of at least 2 nm, or at least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at least 700 nm, or at least 800 nm, or at least 900 nm. The coating can be up to 1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most 500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or at most 100 nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nm thick. Specific thickness ranges composed of any one of the minimum thicknesses expressed above, plus any equal or greater one of the maximum thicknesses expressed above, are expressly contemplated. The thickness of the SiOx or other coating can be measured, for example, by transmission electron microscopy (TEM), and its composition can be measured by X-ray photoelectron spectroscopy (XPS).
[00196] VII. It is contemplated that the choice of the material to be barred from permeating the coating and the nature of the SiOx coating applied can affect its barrier efficacy. For example, two examples of material commonly intended to be barred are oxygen and water/water vapor. Materials commonly are a better barrier to one than to the other. This is believed to be so at least in part because oxygen is transmitted through the coating by a different mechanism than water is transmitted.
[00197] VII. Oxygen transmission is affected by the physical features of the coating, such as its thickness, the presence of cracks, and other physical details of the coating. Water
transmission, on the other hand, is believed to commonly be affected by chemical factors, i.e. the material of which the coating is made, more than physical factors. The inventors also believe that at least one of these chemical factors is a substantial concentration of OH moieties in the coating, which leads to a higher transmission rate of water through the barrier. An SiOx coating often contains OH moieties, and thus a physically sound coating containing a high proportion of OH moieties is a better barrier to oxygen than to water. A physically sound carbon-based barrier, such as amorphous carbon or diamond-like carbon (DLC) commonly is a better barrier to water than is a SiOx coating because the carbon-based barrier more commonly has a lower concentration of OH moieties.
[00198] VII. Other factors lead to a preference for an SiOx coating, however, such as its oxygen barrier efficacy and its close chemical resemblance to glass and quartz. Glass and quartz (when used as the base material of a vessel) are two materials long known to present a very high barrier to oxygen and water transmission as well as substantial inertness to many materials commonly carried in vessels. Thus, it is commonly desirable to optimize the water barrier properties such as the water vapor transmission rate (WVTR) of an SiOx coating, rather than choosing a different or additional type of coating to serve as a water transmission barrier.
[00199] VII. Several ways contemplated to improve the WVTR of an SiOx coating are as follow. [00200] VII. The concentration ratio of organic moieties (carbon and hydrogen compounds) to OH moieties in the deposited coating can be increased. This can be done, for example, by increasing the proportion of oxygen in the feed gases (as by increasing the oxygen feed rate or by lowering the feed rate of one or more other constituents). The lowered incidence of OH moieties is believed to result from increasing the degree of reaction of the oxygen feed with the hydrogen in the silicone source to yield more volatile water in the PECVD exhaust and a lower
concentration of OH moieties trapped or incorporated in the coating.
[00201] VII. Higher energy can be applied in the PECVD process, either by raising the plasma generation power level, by applying the power for a longer period, or both. An increase in the applied energy must be employed with care when used to coat a plastic tube or other device, as it also has a tendency to distort the vessel being treated, to the extent the tube absorbs the plasma generation power. This is why RF power is contemplated in the context of present application. Distortion of the medical devices can be reduced or eliminated by employing the energy in a series of two or more pulses separated by cooling time, by cooling the vessels while applying energy, by applying the coating in a shorter time (commonly thus making it thinner), by selecting a frequency of the applied coating that is absorbed minimally by the base material selected for being coated, and/or by applying more than one coating, with time in between the respective energy application steps. For example, high power pulsing can be used with a duty cycle of 1 millisecond on, 99 milliseconds off, while continuing to feed the process gas. The process gas is then the coolant, as it keeps flowing between pulses. Another alternative is to reconfigure the power applicator, as by adding magnets to confine the plasma increase the effective power application (the power that actually results in incremental coating, as opposed to waste power that results in heating or unwanted coating). This expedient results in the application of more coating-formation energy per total Watt-hour of energy applied. See for example U.S. Patent 5,904,952.
[00202] VII. An oxygen post-treatment of the coating can be applied to remove OH moieties from the previously-deposited coating. This treatment is also contemplated to remove residual volatile organosilicon compounds or silicones or oxidize the coating to form additional SiOx.
[00203] VII. The plastic base material tube can be preheated. [00204] VII. A different volatile source of silicon, such as hexamethyldisilazane (HMDZ), can be used as part or all of the silicone feed. It is contemplated that changing the feed gas to HMDZ will address the problem because this compound has no oxygen moieties in it, as supplied. It is contemplated that one source of OH moieties in the HMDSO-sourced coating is hydrogenation of at least some of the oxygen atoms present in unreacted HMDSO.
[00205] VII. A composite coating can be used, such as a carbon-based coating combined with SiOx. This can be done, for example, by changing the reaction conditions or by adding a substituted or unsubstituted hydrocarbon, such as an alkane, alkene, or alkyne, to the feed gas as well as an organosilicon-based compound. See for example U.S. Patent 5,904,952, which states in relevant part: "For example, inclusion of a lower hydrocarbon such as propylene provides carbon moieties and improves most properties of the deposited films (except for light transmission), and bonding analysis indicates the film to be silicon dioxide in nature. Use of methane, methanol, or acetylene, however, produces films that are silicone in nature. The inclusion of a minor amount of gaseous nitrogen to the gas stream provides nitrogen moieties in the deposited films and increases the deposition rate, improves the transmission and reflection optical properties on glass, and varies the index of refraction in response to varied amounts of N2. The addition of nitrous oxide to the gas stream increases the deposition rate and improves the optical properties, but tends to decrease the film hardness."
[00206] VII. A diamond-like carbon (DLC) coating can be formed as the primary or sole coating deposited. This can be done, for example, by changing the reaction conditions or by feeding methane, hydrogen, and helium to a PECVD process. These reaction feeds have no oxygen, so no OH moieties can be formed. For one example, an SiOx coating can be applied on the interior of a tube or syringe barrel and an outer DLC coating can be applied on the exterior contact surface of a tube or syringe barrel. Or, the SiOx and DLC coatings can both be applied as a single layer or plural layers of an interior tube or syringe barrel coating.
[00207] VII. Referring to FIG. 2, the barrier or other type of coating 90 reduces the transmission of atmospheric gases into the vessel 80 through its interior contact surface 88. Or, the barrier or other type of coating 90 reduces the contact of the contents of the vessel 80 with the interior contact surface 88. The barrier or other type of coating can comprise, for example, SiOx, amorphous (for example, diamond-like) carbon, or a combination of these. [00208] VII. Any coating described herein can be used for coating a contact surface, for example a plastic contact surface. It can further be used as a barrier layer, for example as a barrier against a gas or liquid, optionally against water vapor, oxygen and/or air. It can also be used for preventing or reducing mechanical and/or chemical effects which the coated contact surface would have on a compound or composition if the contact surface were uncoated. For example, it can prevent or reduce the precipitation of a compound or composition, for example insulin precipitation or blood clotting or platelet activation.
VILA. Evacuated Blood Collection Vessels
VILA.l. Tubes
[00209] VILA.L Referring to FIG. 2, more details of the vessel such as 80 are shown. The illustrated vessel 80 can be generally tubular, having an opening 82 at one end of the vessel, opposed by a closed end 84. The vessel 80 also has a wall 86 defining an interior contact surface 88. One example of the vessel 80 is a medical sample tube, such as an evacuated blood collection tube, as commonly is used by a phlebotomist for receiving a venipuncture sample of a patient's blood for use in a medical laboratory.
[00210] VILA. l. The vessel 80 can be made, for example, of thermoplastic material. Some examples of suitable thermoplastic material are polyethylene terephthalate or a polyolefin such as polypropylene or a cyclic polyolefin copolymer.
[00211] VILA. l. The vessel 80 can be made by any suitable method, such as by injection molding, by blow molding, by machining, by fabrication from tubing stock, or by other suitable means. PECVD can be used to form a coating on the internal contact surface of SiOx.
[00212] VILA.1. If intended for use as an evacuated blood collection tube, the vessel 80 desirably can be strong enough to withstand a substantially total internal vacuum substantially without deformation when exposed to an external pressure of 760 Torr or atmospheric pressure and other coating processing conditions. This property can be provided, in a thermoplastic vessel 80, by providing a vessel 80 made of suitable materials having suitable dimensions and a glass transition temperature higher than the processing temperature of the coating process, for example a cylindrical wall 86 having sufficient wall thickness for its diameter and material. [00213] VH.A. l. Medical vessels or containers like sample collection tubes and syringes are relatively small and are injection molded with relatively thick walls, which renders them able to be evacuated without being crushed by the ambient atmospheric pressure. They are thus stronger than carbonated soft drink bottles or other larger or thinner- walled plastic containers. Since sample collection tubes designed for use as evacuated vessels typically are constructed to withstand a full vacuum during storage, they can be used as vacuum chambers.
[00214] Vn.A. l. Such adaptation of the vessels to be their own vacuum chambers might eliminate the need to place the vessels into a vacuum chamber for PECVD treatment, which typically is carried out at very low pressure. The use of a vessel as its own vacuum chamber can result in faster processing time (since loading and unloading of the parts from a separate vacuum chamber is not necessary) and can lead to simplified equipment configurations. Furthermore, a vessel holder is contemplated, for certain embodiments, that will hold the device (for alignment to gas tubes and other apparatus), seal the device (so that the vacuum can be created by attaching the vessel holder to a vacuum pump) and move the device between molding and subsequent processing steps.
[00215] Vn.A. l. A vessel 80 used as an evacuated blood collection tube should be able to withstand external atmospheric pressure, while internally evacuated to a reduced pressure useful for the intended application, without a substantial volume of air or other atmospheric gas leaking into the tube (as by bypassing the closure) or permeating through the wall 86 during its shelf life. If the as-molded vessel 80 cannot meet this requirement, it can be processed by coating the interior contact surface 88 with a barrier or other type of coating 90. It is desirable to treat and/or coat the interior contact surfaces of these devices (such as sample collection tubes and syringe barrels) to impart various properties that will offer advantages over existing polymeric devices and/or to mimic existing glass products. It is also desirable to measure various properties of the devices before and/or after treatment or coating.
VILA.l.a. Coating Deposited from an Organosilicon Precursor Made By In Situ
Polymerizing Organosilicon Precursor
[00216] VILA.1.a. A process is contemplated for applying a lubricity layer characterized as defined in the Definition Section on a substrate, for example the interior of the barrel of a syringe, comprising applying one of the described precursors on or in the vicinity of a substrate at a thickness of 1 to 5000 nm, optionally 10 to 1000 nm, optionally 10-200 nm, optionally 20 to 100 nm thick and crosslinking or polymerizing (or both) the coating, optionally in a PECVD process, to provide a lubricated contact surface. The coating applied by this process is also contemplated to be new.
[00217] VILA.1. a. A coating of SiwOxCyHz as defined in the Definition Section can have utility as a hydrophobic layer. Coatings of this kind are contemplated to be hydrophobic, independent of whether they function as lubricity layers. A coating or treatment is defined as "hydrophobic" if it lowers the wetting tension of a contact surface, compared to the
corresponding uncoated or untreated contact surface. Hydrophobicity is thus a function of both the untreated substrate and the treatment.
[00218] VILA.1.a. The degree of hydrophobicity of a coating can be varied by varying its composition, properties, or deposition method. For example, a coating of SiOx having little or no hydrocarbon content is more hydrophilic than a coating of SiwOxCyHz as defined in the Definition Section. Generally speaking, the higher the C-Hx (e.g. CH, CH2, or CH3) moiety content of the coating, either by weight, volume, or molarity, relative to its silicon content, the more hydrophobic the coating.
[00219] VILA.1.a. A hydrophobic layer can be very thin, having a thickness of at least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at least 700 nm, or at least 800 nm, or at least 900 nm. The coating can be up to 1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most 500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or at most 100 nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nm thick. Specific thickness ranges composed of any one of the minimum thicknesses expressed above, plus any equal or greater one of the maximum thicknesses expressed above, are expressly contemplated.
[00220] VILA.1.a. One utility for such a hydrophobic layer is to isolate a thermoplastic tube wall, made for example of polyethylene terephthalate (PET), from blood collected within the tube. The hydrophobic layer can be applied on top of a hydrophilic SiOx coating on the internal contact surface of the tube. The SiOx coating increases the barrier properties of the thermoplastic tube and the hydrophobic layer changes the contact surface energy of blood contact surface with the tube wall. The hydrophobic layer can be made by providing a precursor selected from those identified in this specification. For example, the hydrophobic layer precursor can comprise hexamethyldisiloxane (HMDSO), octamethylcyclotetrasiloxane (OMCTS), or
tetramethyldisiloxane (TMDSO).
[00221] VILA.1.a. Another use for a hydrophobic layer is to prepare a glass cell preparation tube. The tube has a wall defining a lumen, a hydrophobic layer in the internal contact surface of the glass wall, and contains a citrate reagent. The hydrophobic layer can be made by providing a precursor selected from those identified elsewhere in this specification. For another example, the hydrophobic layer precursor can comprise hexamethyldisiloxane (HMDSO) or
octamethylcyclotetrasiloxane (OMCTS). Another source material for hydrophobic layers is an alkyl trimethoxysilane of the formula:
R-Si(OCH3)3
in which R is a hydrogen atom or an organic substituent, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, epoxide, or others. Combinations of two or more of these are also contemplated.
[00222] VILA.1. a. Combinations of acid or base catalysis and heating, using an alkyl trimethoxysilane precursor as described above, can condense the precursor (removing ROH byproducts) to form crosslinked polymers, which can optionally be further crosslinked via an alternative method. One specific example is by Shimojima et. al. J. Mater. Chem., 2007, 17, 658 - 663.
[00223] VILA.1. a. A lubricity layer, characterized as defined in the Definition Section, can be applied as a subsequent coating after applying an SiOx barrier coating to the interior contact surface 88 of the vessel 80 to provide a lubricity layer, particularly if the lubricity layer is a liquid organosiloxane compound at the end of the coating process.
[00224] VILA.1.a. Optionally, after the lubricity layer is applied, it can be post-cured after the PECVD process. Radiation curing approaches, including UV-initiated (free radial or cationic), electron-beam (E-beam), and thermal as described in Development Of Novel Cycloaliphatic Siloxanes For Thermal And UV-Curable Applications (Ruby Chakraborty Dissertation, can 2008) be utilized.
[00225] VILA.1.a. Another approach for providing a lubricity layer is to use a silicone demolding agent when injection-molding the thermoplastic vessel to be lubricated. For example, it is contemplated that any of the demolding agents and latent monomers causing in-situ thermal lubricity layer formation during the molding process can be used. Or, the aforementioned monomers can be doped into traditional demolding agents to accomplish the same result.
[00226] VILA.1. a. A lubricity layer, characterized as defined in the Definition Section, is particularly contemplated for the internal contact surface of a syringe barrel as further described below. A lubricated internal contact surface of a syringe barrel can reduce the plunger sliding force needed to advance a plunger in the barrel during operation of a syringe, or the breakout force to start a plunger moving after the prefilled syringe plunger has pushed away the intervening lubricant or adhered to the barrel, for example due to decomposition of the lubricant between the plunger and the barrel. As explained elsewhere in this specification, a lubricity layer also can be applied to the interior contact surface 88 of the vessel 80 to improve adhesion of a subsequent coating of SiOx.
[00227] VILA.1. a. Thus, the coating 90 can comprise a layer of SiOx and a lubricity layer and/or hydrophobic layer, characterized as defined in the Definition Section. The lubricity layer and/or hydrophobic layer of SiwOxCyHz can be deposited between the layer of SiOx and the interior contact surface of the vessel. Or, the layer of SiOx can be deposited between the lubricity layer and/or hydrophobic layer and the interior contact surface of the vessel. Or, three or more layers, either alternating or graduated between these two coating compositions: (1) a layer of SiOx and (2) the lubricity layer and/or hydrophobic layer; can also be used. The layer of SiOx can be deposited adjacent to the lubricity layer and/or hydrophobic layer or remotely, with at least one intervening layer of another material. The layer of SiOx can be deposited adjacent to the interior contact surface of the vessel. Or, the lubricity layer and/or hydrophobic layer can be deposited adjacent to the interior contact surface of the vessel.
[00228] VILA.1.a. Another expedient contemplated here, for adjacent layers of SiOx and a lubricity layer and/or hydrophobic layer, is a graded composite of SiwOxCyHz, as defined in the Definition Section. A graded composite can be separate layers of a lubricity layer and/or hydrophobic layer and SiOx with a transition or interface of intermediate composition between them, or separate layers of a lubricity layer and/or hydrophobic layer and SiOx with an intermediate distinct layer of intermediate composition between them, or a single layer that changes continuously or in steps from a composition of a lubricity layer and/or hydrophobic layer to a composition more like SiOx, going through the coating in a normal direction.
[00229] VILA.1. a. The grade in the graded composite can go in either direction. For example, the a lubricity layer and/or hydrophobic layer can be applied directly to the substrate and graduate to a composition further from the contact surface of SiOx. Or, the composition of SiOx can be applied directly to the substrate and graduate to a composition further from the contact surface of a lubricity layer and/or hydrophobic layer. A graduated coating is particularly contemplated if a coating of one composition is better for adhering to the substrate than the other, in which case the better-adhering composition can, for example, be applied directly to the substrate. It is contemplated that the more distant portions of the graded coating can be less compatible with the substrate than the adjacent portions of the graded coating, since at any point the coating is changing gradually in properties, so adjacent portions at nearly the same depth of the coating have nearly identical composition, and more widely physically separated portions at substantially different depths can have more diverse properties. It is also contemplated that a coating portion that forms a better barrier against transfer of material to or from the substrate can be directly against the substrate, to prevent the more remote coating portion that forms a poorer barrier from being contaminated with the material intended to be barred or impeded by the barrier.
[00230] VILA.1. a. The coating, instead of being graded, optionally can have sharp transitions between one layer and the next, without a substantial gradient of composition. Such coatings can be made, for example, by providing the gases to produce a layer as a steady state flow in a non- plasma state, then energizing the system with a brief plasma discharge to form a coating on the substrate. If a subsequent coating is to be applied, the gases for the previous coating are cleared out and the gases for the next coating are applied in a steady-state fashion before energizing the plasma and again forming a distinct layer on the contact surface of the substrate or its outermost previous coating, with little if any gradual transition at the interface. VILA.l.b. Citrate Blood Tube Having Wall Coated With Hydrophobic layer Deposited from an Organosilicon Precursor
[00231] VILA.1.b. Another embodiment is a cell preparation tube having a wall provided with a hydrophobic layer on its inside contact surface and containing an aqueous sodium citrate reagent. The hydrophobic layer can be also be applied on top of a hydrophilic SiOx coating on the internal contact surface of the tube. The SiOx coating increases the barrier properties of the thermoplastic tube and the hydrophobic layer changes the contact surface energy of blood contact surface with the tube wall.
[00232] VILA. l.b. The wall is made of thermoplastic material having an internal contact surface defining a lumen.
[00233] VILA.1.b. A blood collection tube according to the embodiment VILA.1.b can have a first layer of SiOx on the internal contact surface of the tube, applied as explained in this specification, to function as an oxygen barrier and extend the shelf life of an evacuated blood collection tube made of thermoplastic material. A second layer of a hydrophobic layer, characterized as defined in the Definition Section, can then be applied over the barrier layer on the internal contact surface of the tube to provide a hydrophobic contact surface. The coating is effective to reduce the platelet activation of blood plasma treated with a sodium citrate additive and exposed to the inner contact surface, compared to the same type of wall uncoated.
[00234] VILA.1.b. PECVD is used to form a hydrophobic layer on the internal contact surface, characterized as defined in the Definition Section. Unlike conventional citrate blood collection tubes, the blood collection tube having a hydrophobic layer, characterized as defined in the Definition Section does not require a coating of baked on silicone on the vessel wall, as is conventionally applied to make the contact surface of the tube hydrophobic.
[00235] VILA. l.b. Both layers can be applied using the same precursor, for example HMDSO or OMCTS, and different PECVD reaction conditions.
[00236] VILA.1.b. A sodium citrate anticoagulation reagent is then placed within the tube and it is evacuated and sealed with a closure to produce an evacuated blood collection tube. The components and formulation of the reagent are known to those skilled in the art. The aqueous sodium citrate reagent is disposed in the lumen of the tube in an amount effective to inhibit coagulation of blood introduced into the tube. VILA.l.c. SiOx Barrier Coated Double Wall Plastic Vessel- COC, PET, SiOx layers
[00237] VILA.1.c. Another embodiment is a vessel having a wall at least partially enclosing a lumen. The wall has an interior polymer layer enclosed by an exterior polymer layer. One of the polymer layers is a layer at least 0.1 mm thick of a cyclic olefin copolymer (COC) resin defining a water vapor barrier. Another of the polymer layers is a layer at least 0.1 mm thick of a polyester resin.
[00238] VILA.1.c. The wall includes an oxygen barrier layer of SiOx having a thickness of from about 10 to about 500 angstroms.
[00239] VILA. l.c. In an embodiment, illustrated in FIG. 36, the vessel 80 can be a double- walled vessel having an inner wall 408 and an outer wall 410, respectively made of the same or different materials. One particular embodiment of this type can be made with one wall molded from a cyclic olefin copolymer (COC) and the other wall molded from a polyester such as polyethylene terephthalate (PET), with an SiOx coating as previously described on the interior contact surface 412. As needed, a tie coating or layer can be inserted between the inner and outer walls to promote adhesion between them. An advantage of this wall construction is that walls having different properties can be combined to form a composite having the respective properties of each wall.
[00240] VILA.1.c. As one example, the inner wall 408 can be made of PET coated on the interior contact surface 412 with an SiOx barrier layer, and the outer wall 410 can be made of COC. PET coated with SiOx, as shown elsewhere in this specification, is an excellent oxygen barrier, while COC is an excellent barrier for water vapor, providing a low water vapor transition rate (WVTR). This composite vessel can have superior barrier properties for both oxygen and water vapor. This construction is contemplated, for example, for an evacuated medical sample collection tube that contains an aqueous reagent as manufactured, and has a substantial shelf life, so it should have a barrier preventing transfer of water vapor outward or transfer of oxygen or other gases inward through its composite wall during its shelf life.
[00241] VILA. l.c. As another example, the inner wall 408 can be made of COC coated on the interior contact surface 412 with an SiOx barrier layer, and the outer wall 410 can be made of PET. This construction is contemplated, for example, for a prefilled syringe that contains an aqueous sterile fluid as manufactured. The SiOx barrier will prevent oxygen from entering the syringe through its wall. The COC inner wall will prevent ingress or egress of other materials such as water, thus preventing the water in the aqueous sterile fluid from leaching materials from the wall material into the syringe. The COC inner wall is also contemplated to prevent water derived from the aqueous sterile fluid from passing out of the syringe (thus undesirably concentrating the aqueous sterile fluid), and will prevent non-sterile water or other fluids outside the syringe from entering through the syringe wall and causing the contents to become non- sterile. The COC inner wall is also contemplated to be useful for decreasing the breaking force or friction of the plunger against the inner wall of a syringe.
VILA.l.d. Method of Making Double Wall Plastic Vessel- COC, PET, SiOx Layers
[00242] VILA.1.d. Another embodiment is a method of making a vessel having a wall having an interior polymer layer enclosed by an exterior polymer layer, one layer made of COC and the other made of polyester. The vessel is made by a process including introducing COC and polyester resin layers into an injection mold through concentric injection nozzles.
[00243] VILA. l.d. An optional additional step is applying an amorphous carbon coating to the vessel by PECVD, as an inside coating, an outside coating, or as an interlayer coating located between the layers.
[00244] VILA. l.d. An optional additional step is applying an SiOx barrier layer to the inside of the vessel wall, where SiOx is defined as before. Another optional additional step is post- treating the SiOx layer with a process gas consisting essentially of oxygen and essentially free of a volatile silicon compound.
[00245] VILA.1.d. Optionally, the SiOx coating can be formed at least partially from a silazane feed gas.
[00246] VILA. l.d. The vessel 80 shown in FIG. 36 can be made from the inside out, for one example, by injection molding the inner wall in a first mold cavity, then removing the core and molded inner wall from the first mold cavity to a second, larger mold cavity, then injection molding the outer wall against the inner wall in the second mold cavity. Optionally, a tie layer can be provided to the exterior contact surface of the molded inner wall before over-molding the outer wall onto the tie layer. [00247] VH.A. l.d. Or, the vessel 80 shown in FIG. 36 can be made from the outside in, for one example, by inserting a first core in the mold cavity, injection molding the outer wall in the mold cavity, then removing the first core from the molded first wall and inserting a second, smaller core, then injection molding the inner wall against the outer wall still residing in the mold cavity. Optionally, a tie layer can be provided to the interior contact surface of the molded outer wall before over-molding the inner wall onto the tie layer.
[00248] VH.A. l.d. Or, the vessel 80 shown in FIG. 36 can be made in a two shot mold. This can be done, for one example, by injection molding material for the inner wall from an inner nozzle and the material for the outer wall from a concentric outer nozzle. Optionally, a tie layer can be provided from a third, concentric nozzle disposed between the inner and outer nozzles. The nozzles can feed the respective wall materials simultaneously. One useful expedient is to begin feeding the outer wall material through the outer nozzle slightly before feeding the inner wall material through the inner nozzle. If there is an intermediate concentric nozzle, the order of flow can begin with the outer nozzle and continue in sequence from the intermediate nozzle and then from the inner nozzle. Or, the order of beginning feeding can start from the inside nozzle and work outward, in reverse order compared to the preceding description.
VILA.l.e. Barrier Coating Made Of Glass
[00249] VILA. l.e. Another embodiment is a vessel including a vessel, a barrier coating, and a closure. The vessel is generally tubular and made of thermoplastic material. The vessel has a mouth and a lumen bounded at least in part by a wall having an inner contact surface interfacing with the lumen. There is an at least essentially continuous barrier coating made of glass on the inner contact surface of the wall. A closure covers the mouth and isolates the lumen of the vessel from ambient air.
[00250] VILA. l.e. The vessel 80 can also be made, for example of glass of any type used in medical or laboratory applications, such as soda-lime glass, borosilicate glass, or other glass formulations. Other vessels having any shape or size, made of any material, are also
contemplated for use in the system 20. One function of coating a glass vessel can be to reduce the ingress of ions in the glass, either intentionally or as impurities, for example sodium, calcium, or others, from the glass to the contents of the vessel, such as a reagent or blood in an evacuated blood collection tube. Another function of coating a glass vessel in whole or in part, such as selectively at contact surfaces contacted in sliding relation to other parts, is to provide lubricity to the coating, for example to ease the insertion or removal of a stopper or passage of a sliding element such as a piston in a syringe. Still another reason to coat a glass vessel is to prevent a reagent or intended sample for the vessel, such as blood, from sticking to the wall of the vessel or an increase in the rate of coagulation of the blood in contact with the wall of the vessel.
[00251] VILA. I.e. i. A related embodiment is a vessel as described in the previous paragraph, in which the barrier coating is made of soda lime glass, borosilicate glass, or another type of glass.
VII.A.2. Stoppers
[00252] VII.A.2. FIGS. 23-25 illustrate a vessel 268, which can be an evacuated blood collection tube, having a closure 270 to isolate the lumen 274 from the ambient environment. The closure 270 comprises a interior-facing contact surface 272 exposed to the lumen 274 of the vessel 268 and a wall-contacting contact surface 276 that is in contact with the inner contact surface 278 of the vessel wall 280. In the illustrated embodiment the closure 270 is an assembly of a stopper 282 and a shield 284.
VII.A.2.a. Method of Applying Lubricity layer to Stopper In Vacuum Chamber
[00253] VILA.2. a. Another embodiment is a method of applying a coating on an elastomeric stopper such as 282. The stopper 282, separate from the vessel 268, is placed in a substantially evacuated chamber. A reaction mixture is provided including plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas. Plasma is formed in the reaction mixture, which is contacted with the stopper. A lubricity and/or hydrophobic layer, characterized as defined in the Definition Section, is deposited on at least a portion of the stopper.
[00254] VILA.2. a. In the illustrated embodiment, the wall-contacting contact surface 276 of the closure 270 is coated with a lubricity layer 286.
[00255] VILA.2. a. In some embodiments, the lubricity and/or hydrophobic layer,
characterized as defined in the Definition Section, is effective to reduce the transmission of one or more constituents of the stopper, such as a metal ion constituent of the stopper, or of the vessel wall, into the vessel lumen. Certain elastomeric compositions of the type useful for fabricating a stopper 282 contain trace amounts of one or more metal ions. These ions sometimes should not be able to migrate into the lumen 274 or come in substantial quantities into contact with the vessel contents, particularly if the sample vessel 268 is to be used to collect a sample for trace metal analysis. It is contemplated for example that coatings containing relatively little organic content, i.e. where y and z of SiwOxCyHz as defined in the Definition Section are low or zero, are particularly useful as a metal ion barrier in this application. Regarding silica as a metal ion barrier see, for example, Anupama Mallikarjunan, Jasbir Juneja, Guangrong Yang, Shyam P. Murarka, and Toh-Ming Lu, The Effect of Interfacial Chemistry on Metal Ion Penetration into Polymeric Films, Mat. Res. Soc. Symp. Proa, Vol. 734, pp. B9.60.1 to B9.60.6 (Materials Research Society, 2003); U.S. Patents 5578103 and 6200658, and European Appl. EP0697378 A2, which are all incorporated here by reference. It is contemplated, however, that some organic content can be useful to provide a more elastic coating and to adhere the coating to the elastomeric contact surface of the stopper 282.
[00256] VILA.2. a. In some embodiments, the lubricity and/or hydrophobic layer, characterized as defined in the Definition Section, can be a composite of material having first and second layers, in which the first or inner layer 288 interfaces with the elastomeric stopper 282 and is effective to reduce the transmission of one or more constituents of the stopper 282 into the vessel lumen. The second layer 286 can interface with the inner wall 280 of the vessel and is effective as a lubricity layer to reduce friction between the stopper 282 and the inner wall 280 of the vessel when the stopper 282 is seated on or in the vessel 268. Such composites are described in connection with syringe coatings elsewhere in this specification.
[00257] VILA.2. a. Or, the first and second layers 288 and 286 are defined by a coating of graduated properties, in which the values of y and z defined in the Definition Section are greater in the first layer than in the second layer.
[00258] VILA.2. a. The lubricity and/or hydrophobic layer can be applied, for example, by PECVD substantially as previously described. The lubricity and/or hydrophobic layer can be, for example, between 0.5 and 5000 nm (5 to 50,000 Angstroms) thick, or between 1 and 5000 nm thick, or between 5 and 5000 nm thick, or between 10 and 5000 nm thick, or between 20 and 5000 nm thick, or between 50 and 5000 nm thick, or between 100 and 5000 nm thick, or between 200 and 5000 nm thick, or between 500 and 5000 nm thick, or between 1000 and 5000 nm thick, or between 2000 and 5000 nm thick, or between 3000 and 5000 nm thick, or between 4000 and 10,000 nm thick.
[00259] VILA.2. a. Certain advantages are contemplated for plasma coated lubricity layers, versus the much thicker (one micron or greater) conventional spray applied silicone lubricants. Plasma coatings have a much lower migratory potential to move into blood versus sprayed or micron-coated silicones, both because the amount of plasma coated material is much less and because it can be more intimately applied to the coated contact surface and better bonded in place.
[00260] VILA.2. a. Nanocoatings, as applied by PECVD, are contemplated to offer lower resistance to sliding of an adjacent contact surface or flow of an adjacent fluid than micron coatings, as the plasma coating tends to provide a smoother contact surface.
[00261] VILA.2. a. Still another embodiment is a method of applying a coating of a lubricity and/or hydrophobic layer on an elastomeric stopper. The stopper can be used, for example, to close the vessel previously described. The method includes several parts. A stopper is placed in a substantially evacuated chamber. A reaction mixture is provided comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas. Plasma is formed in the reaction mixture. The stopper is contacted with the reaction mixture, depositing the coating of a lubricity and/or hydrophobic layer on at least a portion of the stopper.
[00262] VILA.2. a. In practicing this method, to obtain higher values of y and z as defined in the Definition Section, it is contemplated that the reaction mixture can comprise a hydrocarbon gas, as further described above and below. Optionally, the reaction mixture can contain oxygen, if lower values of y and z or higher values of x are contemplated. Or, particularly to reduce oxidation and increase the values of y and z, the reaction mixture can be essentially free of an oxidizing gas.
[00263] VILA.2. a. In practicing this method to coat certain embodiments of the stopper such as the stopper 282, it is contemplated to be unnecessary to project the reaction mixture into the concavities of the stopper. For example, the wall-contacting and interior facing contact surfaces 276 and 272 of the stopper 282 are essentially convex, and thus readily treated by a batch process in which a multiplicity of stoppers such as 282 can be located and treated in a single substantially evacuated reaction chamber. It is further contemplated that in some embodiments the coatings 286 and 288 do not need to present as formidable a barrier to oxygen or water as the barrier coating on the interior contact surface 280 of the vessel 268, as the material of the stopper 282 can serve this function to a large degree.
[00264] VILA.2. a. Many variations of the stopper and the stopper coating process are contemplated. The stopper 282 can be contacted with the plasma. Or, the plasma can be formed upstream of the stopper 282, producing plasma product, and the plasma product can be contacted with the stopper 282. The plasma can be formed by exciting the reaction mixture with electromagnetic energy and/or microwave energy.
[00265] VILA.2. a. Variations of the reaction mixture are contemplated. The plasma forming gas can include an inert gas. The inert gas can be, for example, argon or helium, or other gases described in this disclosure. The organosilicon compound gas can be, or include, HMDSO, OMCTS, any of the other organosilicon compounds mentioned in this disclosure, or a combination of two or more of these. The oxidizing gas can be oxygen or the other gases mentioned in this disclosure, or a combination of two or more of these. The hydrocarbon gas can be, for example, methane, methanol, ethane, ethylene, ethanol, propane, propylene, propanol, acetylene, or a combination of two or more of these.
VII.A.2.b. Applying by PECVD a Coating of Group III or IV Element and Carbon on a Stopper
[00266] VII.A.2.b. Another embodiment is a method of applying a coating of a composition including carbon and one or more elements of Groups III or IV on an elastomeric stopper. To carry out the method, a stopper is located in a deposition chamber.
[00267] VII.A.2.b. A reaction mixture is provided in the deposition chamber, including a plasma forming gas with a gaseous source of a Group III element, a Group IV element, or a combination of two or more of these. The reaction mixture optionally contains an oxidizing gas and optionally contains a gaseous compound having one or more C-H bonds. Plasma is formed in the reaction mixture, and the stopper is contacted with the reaction mixture. A coating of a Group III element or compound, a Group IV element or compound, or a combination of two or more of these is deposited on at least a portion of the stopper. VII.A.3. Stoppered Plastic Vessel Having Barrier Coating Effective To Provide 95% Vacuum Retention for 24 Months
[00268] VII.A.3. Another embodiment is a vessel including a vessel, a barrier coating, and a closure. The vessel is generally tubular and made of thermoplastic material. The vessel has a mouth and a lumen bounded at least in part by a wall. The wall has an inner contact surface interfacing with the lumen. An at least essentially continuous barrier coating is applied on the inner contact surface of the wall. The barrier coating is effective to provide a substantial shelf life. A closure is provided covering the mouth of the vessel and isolating the lumen of the vessel from ambient air.
[00269] VII.A.3. Referring to FIGS. 23-25, a vessel 268 such as an evacuated blood collection tube or other vessel is shown.
[00270] VII.A.3. The vessel is, in this embodiment, a generally tubular vessel having an at least essentially continuous barrier coating and a closure. The vessel is made of thermoplastic material having a mouth and a lumen bounded at least in part by a wall having an inner contact surface interfacing with the lumen. The barrier coating is deposited on the inner contact surface of the wall, and is effective to maintain at least 95%, or at least 90%, of the initial vacuum level of the vessel for a shelf life of at least 24 months, optionally at least 30 months, optionally at least 36 months. The closure covers the mouth of the vessel and isolates the lumen of the vessel from ambient air.
[00271] VII.A.3. The closure, for example the closure 270 illustrated in the Figures or another type of closure, is provided to maintain a partial vacuum and/or to contain a sample and limit or prevent its exposure to oxygen or contaminants. FIGS. 23-25 are based on figures found in U.S. Patent No. 6,602,206, but the present discovery is not limited to that or any other particular type of closure.
[00272] VII.A.3. The closure 270 comprises a interior-facing contact surface 272 exposed to the lumen 274 of the vessel 268 and a wall-contacting contact surface 276 that is in contact with the inner contact surface 278 of the vessel wall 280. In the illustrated embodiment the closure 270 is an assembly of a stopper 282 and a shield 284.
[00273] VII.A.3. In the illustrated embodiment, the stopper 282 defines the wall-contacting contact surface 276 and the inner contact surface 278, while the shield is largely or entirely outside the stoppered vessel 268, retains and provides a grip for the stopper 282, and shields a person removing the closure 270 from being exposed to any contents expelled from the vessel 268, such as due to a pressure difference inside and outside of the vessel 268 when the vessel 268 is opened and air rushes in or out to equalize the pressure difference.
[00274] VILA.3. It is further contemplated that the coatings on the vessel wall 280 and the wall contacting contact surface 276 of the stopper can be coordinated. The stopper can be coated with a lubricity silicone layer, and the vessel wall 280, made for example of PET or glass, can be coated with a harder SiOx layer, or with an underlying SiOx layer and a lubricity overcoat.
VII.B. Syringes
[00275] VII.B. The foregoing description has largely addressed applying a barrier coating to a tube with one permanently closed end, such as a blood collection tube or, more generally, a specimen receiving tube 80. The apparatus is not limited to such a device.
[00276] VII.B. Another example of a suitable vessel, shown in FIGS 20-22, is a syringe barrel 250 for a medical syringe 252. Such syringes 252 are sometimes supplied prefilled with saline solution, a pharmaceutical preparation, or the like for use in medical techniques. Pre-filled syringes 252 are also contemplated to benefit from an SiOx barrier or other type of coating on the interior contact surface 254 to keep the contents of the prefilled syringe 252 out of contact with the plastic of the syringe, for example of the syringe barrel 250 during storage. The barrier or other type of coating can be used to avoid leaching components of the plastic into the contents of the barrel through the interior contact surface 254.
[00277] VII.B. A syringe barrel 250 as molded commonly can be open at both the back end 256, to receive a plunger 258, and at the front end 260, to receive a hypodermic needle, a nozzle, or tubing for dispensing the contents of the syringe 252 or for receiving material into the syringe 252. But the front end 260 can optionally be capped and the plunger 258 optionally can be fitted in place before the prefilled syringe 252 is used, closing the barrel 250 at both ends. A cap 262 can be installed either for the purpose of processing the syringe barrel 250 or assembled syringe, or to remain in place during storage of the prefilled syringe 252, up to the time the cap 262 is removed and (optionally) a hypodermic needle or other delivery conduit is fitted on the front end 260 to prepare the syringe 252 for use. VII.B.l. Assemblies
[00278] VII.B.l. FIG. 42 also shows an alternative syringe barrel construction usable, for example, with the embodiments of FIGS. 21, 26, 28, 30, and 34 and adapted for use with the vessel holder 450 of that Figure..
[00279] VII.B.l. FIG. 50 is an exploded view and FIG. 51 is an assembled view of a syringe. The syringe barrel can be processed with the vessel treatment and inspection apparatus of FIGS. 1-22, 26-28, 33-35, 37-39, 44, and 53-54.
[00280] VII.B.l. The installation of a cap 262 makes the barrel 250 a closed-end vessel that can be provided with an SiOx barrier or other type of coating on its interior contact surface 254 in the previously illustrated apparatus, optionally also providing a coating on the interior 264 of the cap and bridging the interface between the cap interior 264 and the barrel front end 260. Suitable apparatus adapted for this use is shown, for example, in FIG. 21, which is analogous to FIG. 2 except for the substitution of the capped syringe barrel 250 for the vessel 80 of FIG. 2. VII.B.
[00281] VII.B.l FIG. 52 is a view similar to FIG. 42, but showing a syringe barrel being treated that has no flange or finger stops 440. The syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-51, and 53-54.
VII.B. l.a. Syringe Having Barrel Coated With Lubricity layer Deposited from an Organosilicon Precursor
[00282] VII.B. l.a. Still another embodiment is a vessel having a lubricity layer,
characterized as defined in the Definition Section, of the type made by the following process.
[00283] VII.B. l.a. A precursor is provided as defined above.
[00284] VII.B. l.a. The precursor is applied to a substrate under conditions effective to form a coating. The coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
[00285] VII.B. l.a. Respecting any of the Embodiments VII and sub-parts, optionally the applying step is carried out by vaporizing the precursor and providing it in the vicinity of the substrate.
[00286] VII.B. l.a. Respecting any of the Embodiments VII.A. l.a.i, optionally a plasma, optionally a non-hollow-cathode plasma, is formed in the vicinity of the substrate. Optionally, the precursor is provided in the substantial absence of oxygen. Optionally, the precursor is provided in the substantial absence of a carrier gas. Optionally, the precursor is provided in the substantial absence of nitrogen. Optionally, the precursor is provided at less than 1 Torr absolute pressure. Optionally, the precursor is provided to the vicinity of a plasma emission. Optionally, the precursor its reaction product is applied to the substrate at a thickness of 1 to 5000 nm thick, or 10 to 1000 nm thick, or 10-200 nm thick, or 20 to 100 nm thick. Optionally, the substrate comprises glass. Optionally, the substrate comprises a polymer, optionally a polycarbonate polymer, optionally an olefin polymer, optionally a cyclic olefin copolymer, optionally a polypropylene polymer, optionally a polyester polymer, optionally a polyethylene terephthalate polymer.
[00287] VH.B.l.a. Optionally, the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes powered, for example, at a RF frequency as defined above, for example a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
[00288] VH.B.l.a. Optionally, the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W. The ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. These power levels are suitable for applying lubricity layers to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
[00289] VH.B.l.a. Another embodiment is a lubricity layer, characterized as defined in the Definition Section, on the inner wall of a syringe barrel. The coating is produced from a PECVD process using the following materials and conditions. A cyclic precursor is optionally employed, selected from a monocyclic siloxane, a polycyclic siloxane, or a combination of two or more of these, as defined elsewhere in this specification for lubricity layers. One example of a suitable cyclic precursor comprises octamethylcyclotetrasiloxane (OMCTS), optionally mixed with other precursor materials in any proportion. Optionally, the cyclic precursor consists essentially of octamethycyclotetrasiloxane (OMCTS), meaning that other precursors can be present in amounts which do not change the basic and novel properties of the resulting lubricity layer, i.e. its reduction of the plunger sliding force or breakout force of the coated contact surface.
[00290] VH.B.l.a. At least essentially no oxygen, as defined in the Definition Section, is added to the process.
[00291] VII.B.1.a. A sufficient plasma generation power input, for example any power level successfully used in one or more working examples of this specification or described in the specification, is provided to induce coating formation.
[00292] VII.B.1. a. The materials and conditions employed are effective to reduce the syringe plunger sliding force or breakout force moving through the syringe barrel at least 25 percent, alternatively at least 45 percent, alternatively at least 60 percent, alternatively greater than 60 percent, relative to an uncoated syringe barrel. Ranges of plunger sliding force or breakout force reduction of from 20 to 95 percent, alternatively from 30 to 80 percent, alternatively from 40 to 75 percent, alternatively from 60 to 70 percent, are contemplated.
[00293] VII.B.1. a. Another embodiment is a vessel having a hydrophobic layer, characterized as defined in the Definition Section, on the inside wall. The coating is made as explained for the lubricant coating of similar composition, but under conditions effective to form a hydrophobic contact surface having a higher contact angle than the untreated substrate.
[00294] VII.B.1. a. Respecting any of the Embodiments VII.A. l.a.ii, optionally the substrate comprises glass or a polymer. The glass optionally is borosilicate glass. The polymer is optionally a polycarbonate polymer, optionally an olefin polymer, optionally a cyclic olefin copolymer, optionally a polypropylene polymer, optionally a polyester polymer, optionally a polyethylene terephthalate polymer.
[00295] VII.B.1. a. Another embodiment is a syringe including a plunger, a syringe barrel, and a lubricity layer, characterized as defined in the Definition Section. The syringe barrel includes an interior contact surface receiving the plunger for sliding. The lubricity layer is disposed on the interior contact surface of the syringe barrel. The lubricity layer is less than 1000 nm thick and effective to reduce the breakout force or the plunger sliding force necessary to move the plunger within the barrel. Reducing the plunger sliding force is alternatively expressed as reducing the coefficient of sliding friction of the plunger within the barrel or reducing the plunger force; these terms are regarded as having the same meaning in this specification.
[00296] VH.B.l.a. The syringe 544 of FIGS. 50-51 comprises a plunger 546 and a syringe barrel 548. The syringe barrel 548 has an interior contact surface 552 receiving the plunger for sliding 546. The interior contact surface 552 of the syringe barrel 548 further comprises a lubricity layer 554, characterized as defined in the Definition Section. The lubricity layer is less than 1000 nm thick, optionally less than 500 nm thick, optionally less than 200 nm thick, optionally less than 100 nm thick, optionally less than 50 nm thick, and is effective to reduce the breakout force necessary to overcome adhesion of the plunger after storage or the plunger sliding force necessary to move the plunger within the barrel after it has broken away. The lubricity layer is characterized by having a plunger sliding force or breakout force lower than that of the uncoated contact surface.
[00297] VH.B.l.a. Any of the above precursors of any type can be used alone or in combinations of two or more of them to provide a lubricity layer.
[00298] VH.B.l.a. In addition to utilizing vacuum processes, low temperature atmospheric (non-vacuum) plasma processes can also be utilized to induce molecular ionization and deposition through precursor monomer vapor delivery optionally in a non-oxidizing atmosphere such as helium or argon. Separately, thermal CVD can be considered via flash thermolysis deposition.
[00299] VH.B.l.a. The approaches above are similar to vacuum PECVD in that the contact surface coating and crosslinking mechanisms can occur simultaneously.
[00300] VH.B.l.a. Yet another expedient contemplated for any coating or coatings described here is a coating that is not uniformly applied over the entire interior 88 of a vessel. For example, a different or additional coating can be applied selectively to the cylindrical portion of the vessel interior, compared to the hemispherical portion of the vessel interior at its closed end 84, or vice versa. This expedient is particularly contemplated for a syringe barrel or a sample collection tube as described below, in which a lubricity layer might be provided on part or all of the cylindrical portion of the barrel, where the plunger or piston or closure slides, and not elsewhere. [00301] VH.B.l.a. Optionally, the precursor can be provided in the presence, substantial absence, or absence of oxygen, in the presence, substantial absence, or absence of nitrogen, or in the presence, substantial absence, or absence of a carrier gas. In one contemplated embodiment, the precursor alone is delivered to the substrate and subjected to PECVD to apply and cure the coating.
[00302] VH.B.l.a. Optionally, the precursor can be provided at less than 1 Torr absolute pressure.
[00303] VH.B.l.a. Optionally, the precursor can be provided to the vicinity of a plasma emission.
[00304] VH.B.l.a. Optionally, the precursor its reaction product can be applied to the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm., or 10-200 nm, or 20 to 100 nm.
[00305] VH.B.l.a. In any of the above embodiments, the substrate can comprise glass, or a polymer, for example one or more of a polycarbonate polymer, an olefin polymer (for example a cyclic olefin copolymer or a polypropylene polymer), or a polyester polymer (for example, a polyethylene terephthalate polymer).
[00306] VH.B.l.a. In any of the above embodiments, the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes powered at a RF frequency as defined in this description.
[00307] VH.B.l.a. In any of the above embodiments, the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with sufficient electric power to generate a lubricity layer. Optionally, the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W. The ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. These power levels are suitable for applying lubricity layers to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
[00308] VH.B.l.a. The coating can be cured, as by polymerizing or crosslinking the coating, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate. Curing can occur during the application process such as PECVD, or can be carried out or at least completed by separate processing.
[00309] VH.B.l.a. Although plasma deposition has been used herein to demonstrate the coating characteristics, alternate deposition methods can be used as long as the chemical composition of the starting material is preserved as much as possible while still depositing a solid film that is adhered to the base substrate.
[00310] VH.B.l.a. For example, the coating material can be applied onto the syringe barrel (from the liquid state) by spraying the coating or dipping the substrate into the coating, where the coating is either the neat precursor a solvent-diluted precursor (allowing the mechanical deposition of a thinner coating). The coating optionally can be crosslinked using thermal energy, UV energy, electron beam energy, plasma energy, or any combination of these.
[00311] VH.B.l.a. Application of a silicone precursor as described above onto a contact surface followed by a separate curing step is also contemplated. The conditions of application and curing can be analogous to those used for the atmospheric plasma curing of pre-coated polyfluoroalkyl ethers, a process practiced under the trademark TriboGlide®. More details of this process can be found at http://www.triboglide.com/process.htm.
[00312] VII.B.l.a. In such a process, the area of the part to be coated can optionally be pre- treated with an atmospheric plasma. This pretreatment cleans and activates the contact surface so that it is receptive to the lubricant that is sprayed in the next step.
[00313] VII.B.l.a. The lubrication fluid, in this case one of the above precursors or a polymerized precursor, is then sprayed on to the contact surface to be treated. For example, IVEK precision dispensing technology can be used to accurately atomize the fluid and create a uniform coating. [00314] VH.B.l.a. The coating is then bonded or crosslinked to the part, again using an atmospheric plasma field. This both immobilizes the coating and improves the lubricant's performance.
[00315] VH.B.l.a. Optionally, the atmospheric plasma can be generated from ambient air in the vessel, in which case no gas feed and no vacuum drawing equipment is needed. Optionally, however, the vessel is at least substantially closed while plasma is generated, to minimize the power requirement and prevent contact of the plasma with contact surfaces or materials outside the vessel.
VII.B.l.a . Lubricity layer: SiOx Barrier, Lubricity Layer, Contact surface Treatment Contact surface treatment
[00316] VH.B.l.a.i. Another embodiment is a syringe comprising a barrel defining a lumen and having an interior contact surface slidably receiving a plunger, i.e. receiving a plunger for sliding contact to the interior contact surface.
[00317] VH.B.l.a.i. The syringe barrel is made of thermoplastic base material.
[00318] VH.B.l.a.i. Optionally, the interior contact surface of the barrel is coated with an SiOx barrier layer as described elsewhere in this specification.
[00319] VH.B.l.a.i. A lubricity layer is applied to the barrel interior contact surface, the plunger, or both, or to the previously applied SiOx barrier layer. The lubricity layer can be provided, applied, and cured as set out in embodiment VH.B.l.a or elsewhere in this
specification.
[00320] VH.B.l.a.i. For example, the lubricity layer can be applied, in any embodiment, by PECVD. The lubricity layer is deposited from an organosilicon precursor, and is less than 1000 nm thick.
[00321] VII.B.l.a.i. A contact surface treatment is carried out on the lubricity layer in an amount effective to reduce the leaching or extractables of the lubricity layer, the thermoplastic base material, or both. The treated contact surface can thus act as a solute retainer. This contact surface treatment can result in a skin coating, e.g. a skin coating which is at least 1 nm thick and less than 100 nm thick, or less than 50 nm thick, or less than 40 nm thick, or less than 30 nm thick, or less than 20 nm thick, or less than 10 nm thick, or less than 5 nm thick, or less than 3 nm thick, or less than 2 nm thick, or less than 1 nm thick, or less than 0.5 nm thick.
[00322] VH.B.l.a.i. As used herein, "leaching" refers to material transferred out of a substrate, such as a vessel wall, into the contents of a vessel, for example a syringe. Commonly, leachables are measured by storing the vessel filled with intended contents, then analyzing the contents to determine what material leached from the vessel wall into the intended contents. "Extraction" refers to material removed from a substrate by introducing a solvent or dispersion medium other than the intended contents of the vessel, to determine what material can be removed from the substrate into the extraction medium under the conditions of the test.
[00323] VH.B.l.a.i. The contact surface treatment resulting in a solute retainer optionally can be a SiOx layer as previously defined in this specification or a hydrophobic layer, characterized as defined in the Definition Section. In one embodiment, the contact surface treatment can be applied by PECVD deposit of SiOx or a hydrophobic layer. Optionally, the contact surface treatment can be applied using higher power or stronger oxidation conditions than used for creating the lubricity layer, or both, thus providing a harder, thinner, continuous solute retainer 539. Contact surface treatment can be less than 100 nm deep, optionally less than 50 nm deep, optionally less than 40 nm deep, optionally less than 30 nm deep, optionally less than 20 nm deep, optionally less than 10 nm deep, optionally less than 5 nm deep, optionally less than 3 nm deep, optionally less than 1 nm deep, optionally less than 0.5 nm deep, optionally between 0.1 and 50 nm deep in the lubricity layer.
[00324] VII.B.l.a.i. The solute retainer is contemplated to provide low solute leaching performance to the underlying lubricity and other layers, including the substrate, as required. This retainer would only need to be a solute retainer to large solute molecules and oligomers (for example siloxane monomers such as HMDSO, OMCTS, their fragments and mobile oligomers derived from lubricants, for example a "leachables retainer") and not a gas (Oi/Ni/CC water vapor) barrier layer. A solute retainer can, however, also be a gas barrier (e.g. the SiOx coating according to present invention. One can create a good leachable retainer without gas barrier performance, either by vacuum or atmospheric-based PECVD processes. It is desirable that the "leachables barrier" will be sufficiently thin that, upon syringe plunger movement, the plunger will readily penetrate the "solute retainer" exposing the sliding plunger nipple to the lubricity layer immediately below to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
[00325] VH.B.l.a.i. In another embodiment, the contact surface treatment can be performed by oxidizing the contact surface of a previously applied lubricity layer, as by exposing the contact surface to oxygen in a plasma environment. The plasma environment described in this specification for forming SiOx coatings can be used. Or, atmospheric plasma conditions can be employed in an oxygen-rich environment.
[00326] VH.B.l.a.i. The lubricity layer and solute retainer, however formed, optionally can be cured at the same time. In another embodiment, the lubricity layer can be at least partially cured, optionally fully cured, after which the contact surface treatment can be provided, applied, and the solute retainer can be cured.
[00327] VH.B.l.a.i. The lubricity layer and solute retainer are composed, and present in relative amounts, effective to provide a breakout force, plunger sliding force, or both that is less than the corresponding force required in the absence of the lubricity layer and contact surface treatment. In other words, the thickness and composition of the solute retainer are such as to reduce the leaching of material from the lubricity layer into the contents of the syringe, while allowing the underlying lubricity layer to lubricate the plunger. It is contemplated that the solute retainer will break away easily and be thin enough that the lubricity layer will still function to lubricate the plunger when it is moved.
[00328] VH.B.l.a.i. In one contemplated embodiment, the lubricity and contact surface treatments can be applied on the barrel interior contact surface. In another contemplated embodiment, the lubricity and contact surface treatments can be applied on the plunger. In still another contemplated embodiment, the lubricity and contact surface treatments can be applied both on the barrel interior contact surface and on the plunger. In any of these embodiments, the optional SiOx barrier layer on the interior of the syringe barrel can either be present or absent.
[00329] VH.B.l.a.i. One embodiment contemplated is a plural-layer, e.g. a 3-layer, configuration applied to the inside contact surface of a syringe barrel. Layer 1 can be an SiOx gas barrier made by PECVD of HMDSO, OMCTS, or both, in an oxidizing atmosphere. Such an atmosphere can be provided, for example, by feeding HMDSO and oxygen gas to a PECVD coating apparatus as described in this specification. Layer 2 can be a lubricity layer using OMCTS applied in a non-oxidizing atmosphere. Such a non-oxidizing atmosphere can be provided, for example, by feeding OMCTS to a PECVD coating apparatus as described in this specification, optionally in the substantial or complete absence of oxygen. A subsequent solute retainer can be formed by a treatment forming a thin skin layer of SiOx or a hydrophobic layer as a solute retainer using higher power and oxygen using OMCTS and/or HMDSO.
[00330] VH.B.l.a.i. Certain of these plural-layer coatings are contemplated to have one or more of the following optional advantages, at least to some degree. They can address the reported difficulty of handling silicone, since the solute retainer can confine the interior silicone and prevent if from migrating into the contents of the syringe or elsewhere, resulting in fewer silicone particles in the deliverable contents of the syringe and less opportunity for interaction between the lubricity layer and the contents of the syringe. They can also address the issue of migration of the lubricity layer away from the point of lubrication, improving the lubricity of the interface between the syringe barrel and the plunger. For example, the break-free force can be reduced and the drag on the moving plunger can be reduced, or optionally both.
[00331] VH.B.l.a.i. It is contemplated that when the solute retainer is broken, the solute retainer will continue to adhere to the lubricity layer and the syringe barrel, which can inhibit any particles from being entrained in the deliverable contents of the syringe.
[00332] VH.B.l.a.i. Certain of these coatings will also provide manufacturing advantages, particularly if the barrier coating, lubricity layer and contact surface treatment are applied in the same apparatus, for example the illustrated PECVD apparatus. Optionally, the SiOx barrier coating, lubricity layer, and contact surface treatment can all be applied in one PECVD apparatus, thus greatly reducing the amount of handling necessary.
[00333] Further advantages can be obtained by forming the barrier coating, lubricity layer, and solute retainer using the same precursors and varying the process. For example, an SiOx gas barrier layer can be applied using an OMCTS precursor under high power/high 02 conditions, followed by applying a lubricity layer applied using an OMCTS precursor under low power and/or in the substantial or complete absence of oxygen, finishing with a contact surface treatment using an OMCTS precursor under intermediate power and oxygen. VII.B.l.b Syringe having barrel with SiOx coated interior and barrier coated exterior
[00334] VII.B.l.b. Still another embodiment, illustrated in FIG. 50, is a syringe 544 including a plunger 546, a barrel 548, and interior and exterior barrier coatings 554 and 602. The barrel 548 can be made of thermoplastic base material defining a lumen 604. The barrel 548 can have an interior contact surface 552 receiving the plunger for sliding 546 and an exterior contact surface 606. A barrier coating 554 of SiOx, in which x is from about 1.5 to about 2.9, can be provided on the interior contact surface 552 of the barrel 548. A barrier coating 602 of a resin can be provided on the exterior contact surface 606 of the barrel 548.
[00335] VII.B.l.b. In any embodiment, the thermoplastic base material optionally can include a polyolefin, for example polypropylene or a cyclic olefin copolymer (for example the material sold under the trademark TOPAS®), a polyester, for example polyethylene terephthalate, a polycarbonate, for example a bisphenol A polycarbonate thermoplastic, or other materials.
Composite syringe barrels are contemplated having any one of these materials as an outer layer and the same or a different one of these materials as an inner layer. Any of the material combinations of the composite syringe barrels or sample tubes described elsewhere in this specification can also be used.
[00336] VII.B.l.b. In any embodiment, the resin optionally can include polyvinylidene chloride in homopolymer or copolymer form. For example, the PVdC homopolymers (trivial name: Saran) or copolymers described in US Patent 6,165,566, incorporated here by reference, can be employed. The resin optionally can be applied onto the exterior contact surface of the barrel in the form of a latex or other dispersion.
[00337] VII.B.l.b. In any embodiment, the syringe barrel 548 optionally can include a lubricity layer disposed between the plunger and the barrier coating of SiOx. Suitable lubricity layers are described elsewhere in this specification.
[00338] VII.B.l.b. In any embodiment, the lubricity layer optionally can be applied by PECVD and optionally can include material characterized as defined in the Definition Section.
[00339] VII.B.l.b. In any embodiment, the syringe barrel 548 optionally can include a contact surface treatment covering the lubricity layer in an amount effective to reduce the leaching of the lubricity layer, constituents of the thermoplastic base material, or both into the lumen 604. VII.B.l.c Method of Making Syringe having barrel with SiOx coated interior and barrier coated exterior
[00340] VII.B.l.c. Even another embodiment is a method of making a syringe as described in any of the embodiments of part VII.B. l.b, including a plunger, a barrel, and interior and exterior barrier coatings. A barrel is provided having an interior contact surface for receiving the plunger for sliding and an exterior contact surface. A barrier coating of SiOx is provided on the interior contact surface of the barrel by PECVD. A barrier coating of a resin is provided on the exterior contact surface of the barrel. The plunger and barrel are assembled to provide a syringe.
[00341] VII.B.l.c. For effective coating (uniform wetting) of the plastic article with the aqueous latex, it is contemplated to be useful to match the contact surface tension of the latex to the plastic substrate. This can be accomplished by several approaches, independently or combined, for example, reducing the contact surface tension of the latex (with surfactants or solvents), and/or corona pretreatment of the plastic article, and/or chemical priming of the plastic article.
[00342] VII.B.l.c. The resin optionally can be applied via dip coating of the latex onto the exterior contact surface of the barrel, spray coating of the latex onto the exterior contact surface of the barrel, or both, providing plastic-based articles offering improved gas and vapor barrier performance. Polyvinylidene chloride plastic laminate articles can be made that provide significantly improved gas barrier performance versus the non-laminated plastic article.
[00343] VII.B.l.c. In any embodiment, the resin optionally can be heat cured. The resin optionally can be cured by removing water. Water can be removed by heat curing the resin, exposing the resin to a partial vacuum or low-humidity environment, catalytically curing the resin, or other expedients.
[00344] VII.B.l.c. An effective thermal cure schedule is contemplated to provide final drying to permit PVdC crystallization, offering barrier performance. Primary curing can be carried out at an elevated temperature, for example between 180-310°F (82-154°C), of course depending on the heat tolerance of the thermoplastic base material. Barrier performance after the primary cure optionally can be about 85% of the ultimate barrier performance achieved after a final cure. [00345] VH.B.l.c. A final cure can be carried out at temperatures ranging from ambient temperature, such as about 65-75°F (18-24°C) for a long time (such as 2 weeks) to an elevated temperature, such as 122°F (50°C), for a short time, such as four hours.
[00346] VH.B.l.c. The PVdC -plastic laminate articles, in addition to superior barrier performance, are optionally contemplated to provide one or more desirable properties such as colorless transparency, good gloss, abrasion resistance, printability, and mechanical strain resistance.
VII.B.2. Plungers
VII.B.2.a. With Barrier Coated Piston Front Face
[00347] VII.B.2. a. Another embodiment is a plunger for a syringe, including a piston and a push rod. The piston has a front face, a generally cylindrical side face, and a back portion, the side face being configured to movably seat within a syringe barrel. The front face has a barrier coating. The push rod engages the back portion and is configured for advancing the piston in a syringe barrel.
VII.B.2.b. With Lubricity layer Interfacing With Side Face
[00348] VII.B.2.b. Yet another embodiment is a plunger for a syringe, including a piston, a lubricity layer, and a push rod. The piston has a front face, a generally cylindrical side face, and a back portion. The side face is configured to movably seat within a syringe barrel. The lubricity layer interfaces with the side face. The push rod engages the back portion of the piston and is configured for advancing the piston in a syringe barrel.
VII.B.3. Two Piece Syringe and Luer Fitting
[00349] VII.B.3. Another embodiment is a syringe including a plunger, a syringe barrel, and a Luer fitting. The syringe includes a barrel having an interior contact surface receiving the plunger for sliding. The Luer fitting includes a Luer taper having an internal passage defined by an internal contact surface. The Luer fitting is formed as a separate piece from the syringe barrel and joined to the syringe barrel by a coupling. The internal passage of the Luer taper has a barrier coating of SiOx.
[00350] VII.B.3. Referring to FIGS. 50-51, the syringe 544 optionally can include a Luer fitting 556 comprising a Luer taper 558 to receive a cannula mounted on a complementary Luer taper (not shown, conventional). The Luer taper 558 has an internal passage 560 defined by an internal contact surface 562. The Luer fitting 556 optionally is formed as a separate piece from the syringe barrel 548 and joined to the syringe barrel 548 by a coupling 564. As illustrated in FIGS. 50 and 51, the coupling 564 in this instance has a male part 566 and a female part 568 that snap together to secure the Luer fitting in at least substantially leak proof fashion to the barrel 548. The internal contact surface 562 of the Luer taper can include a barrier coating 570 of SiOx. The barrier coating can be less than 100 nm thick and effective to reduce the ingress of oxygen into the internal passage of the Luer fitting. The barrier coating can be applied before the Luer fitting is joined to the syringe barrel. The syringe of FIGS. 50-51 also has an optional locking collar 572 that is internally threaded so to lock the complementary Luer taper of a cannula in place on the taper 558.
VII.B.4. Lubricant Compositions - Lubricity layer Deposited from an Organosilicon Precursor Made By In Situ Polymerizing Organosilicon Precursor
VII.BAa. Product By Process and Lubricity
[00351] VII.B.4. a. Still another embodiment is a lubricity layer. This coating can be of the type made by the following process.
[00352] VII.B.4. a. Any of the precursors mentioned elsewhere in this specification can be used, alone or in combination. The precursor is applied to a substrate under conditions effective to form a coating. The coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
[00353] VII.B.4. a. Another embodiment is a method of applying a lubricity layer. An organosilicon precursor is applied to a substrate under conditions effective to form a coating. The coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
VII.BAb. Product by Process and Analytical Properties
[00354] VII.BAb. Even another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising an organometallic precursor, optionally an organosilicon precursor, optionally a linear siloxane, a linear silazane, a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these. The coating has a density between 1.25 and 1.65 g/cm optionally between 1.35 and 1.55 g/cm 3 , optionally between 1.4 and 1.5 g/cm 3 , optionally between 1.44 and 1.48 g/cm 3 as determined by X-ray reflectivity (XRR).
[00355] VII.B.4.b. Still another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising an organometallic precursor, optionally an organosilicon precursor, optionally a linear siloxane, a linear silazane, a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these. The coating has as an outgas component one or more oligomers containing repeating - (Me)2SiO- moieties, as determined by gas chromatography / mass spectrometry. Optionally, the coating meets the limitations of any of embodiments VII.B.4.a or VII.B.4.b.A.585h. Optionally, the coating outgas component as determined by gas chromatography / mass spectrometry is substantially free of trimethylsilanol.
[00356] VII.B.4.b. Optionally, the coating outgas component can be at least 10 ng/test of oligomers containing repeating -(Me)2SiO- moieties, as determined by gas chromatography / mass spectrometry using the following test conditions:
• GC Column: 30m X 0.25mm DB-5MS (J&W Scientific),
0.25 μιη film thickness
• Flow rate: 1.0 ml/min, constant flow mode
• Detector: Mass Selective Detector (MSD)
• Injection Mode: Split injection (10: 1 split ratio)
• Outgassing Conditions: 1½" (37mm) Chamber, purge for three hour at 85°C, flow 60 ml/min
• Oven temperature: 40°C (5 min.) to 300°C at 10°C/min.; hold for 5 min. at
300°C.
[00357] VII.B.4.b. Optionally, the outgas component can include at least 20 ng/test of oligomers containing repeating -(Me)2SiO- moieties.
[00358] VII.B.4.b. Optionally, the feed gas comprises a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these, for example a monocyclic siloxane, a monocyclic silazane, or any combination of two or more of these, for example octamethylcyclotetrasiloxane.
[00359] VII.BAb. The lubricity layer of any embodiment can have a thickness measured by transmission electron microscopy (TEM) between 1 and 500 nm, optionally between 10 and 500 nm, optionally between 20 and 200 nm, optionally between 20 and 100 nm, optionally between 30 and 100 nm.
[00360] VII.BAb. Another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these. The coating has an atomic concentration of carbon, normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), greater than the atomic concentration of carbon in the atomic formula for the feed gas. Optionally, the coating meets the limitations of embodiments VII.BAa or VII.BAb.A.
[00361] VTI.B Ab. Optionally, the atomic concentration of carbon increases by from 1 to 80 atomic percent (as calculated and based on the XPS conditions in Example 15), alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 50 atomic percent, alternatively from 35 to 45 atomic percent, alternatively from 37 to 41 atomic percent.
[00362] VTI.BAb. An additional aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these. The coating has an atomic concentration of silicon, normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), less than the atomic concentration of silicon in the atomic formula for the feed gas. Optionally, the coating meets the limitations of embodiments VII.BAa or VII.BAb.A.
[00363] VII.BAb. Optionally, the atomic concentration of silicon decreases by from 1 to 80 atomic percent (as calculated and based on the XPS conditions in Example 15), alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 55 atomic percent, alternatively from 40 to 50 atomic percent, alternatively from 42 to 46 atomic percent. [00364] VII.BAb. Lubricity layers having combinations of any two or more properties recited in Section VII.B.4 are also expressly contemplated.
VII.C. Vessels Generally
[00365] VII.C. A coated vessel or container as described herein and/or prepared according to a method described herein can be used for reception and/or storage and/or delivery of a compound or composition. The compound or composition can be sensitive, for example air- sensitive, oxygen-sensitive, sensitive to humidity and/or sensitive to mechanical influences. It can be a biologically active compound or composition, for example a medicament like insulin or a composition comprising insulin. In another aspect, it can be a biological fluid, optionally a bodily fluid, for example blood or a blood fraction. In certain aspects of the present invention, the compound or composition is a product to be administrated to a subject in need thereof, for example a product to be injected, like blood (as in transfusion of blood from a donor to a recipient or reintroduction of blood from a patient back to the patient) or insulin.
[00366] VII.C. A coated vessel or container as described herein and/or prepared according to a method described herein can further be used for protecting a compound or composition contained in its interior space against mechanical and/or chemical effects of the contact surface of the uncoated vessel material. For example, it can be used for preventing or reducing precipitation and/or clotting or platelet activation of the compound or a component of the composition, for example insulin precipitation or blood clotting or platelet activation.
[00367] VII.C. It can further be used for protecting a compound or composition contained in its interior against the environment outside of the vessel, for example by preventing or reducing the entry of one or more compounds from the environment surrounding the vessel into the interior space of the vessel. Such environmental compound can be a gas or liquid, for example an atmospheric gas or liquid containing oxygen, air, and/or water vapor.
[00368] VII.C. A coated vessel as described herein can also be evacuated and stored in an evacuated state. For example, the coating allows better maintenance of the vacuum in comparison to a corresponding uncoated vessel. In one aspect of this embodiment, the coated vessel is a blood collection tube. The tube can also contain an agent for preventing blood clotting or platelet activation, for example EDTA or heparin. [00369] VII.C. Any of the above-described embodiments can be made, for example, by providing as the vessel a length of tubing from about 1 cm to about 200 cm, optionally from about 1 cm to about 150 cm, optionally from about 1 cm to about 120 cm, optionally from about 1 cm to about 100 cm, optionally from about 1 cm to about 80 cm, optionally from about 1 cm to about 60 cm, optionally from about 1 cm to about 40 cm, optionally from about 1 cm to about 30 cm long, and processing it with a probe electrode as described below. Particularly for the longer lengths in the above ranges, it is contemplated that relative motion between the probe and the vessel can be useful during coating formation. This can be done, for example, by moving the vessel with respect to the probe or moving the probe with respect to the vessel.
[00370] VII.C. In these embodiments, it is contemplated that the coating can be thinner or less complete than can be preferred for a barrier coating, as the vessel in some embodiments will not require the high barrier integrity of an evacuated blood collection tube.
[00371] VII.C. As an optional feature of any of the foregoing embodiments the vessel has a central axis.
[00372] VII.C. As an optional feature of any of the foregoing embodiments the vessel wall is sufficiently flexible to be flexed at least once at 20 °C, without breaking the wall, over a range from at least substantially straight to a bending radius at the central axis of not more than 100 times as great as the outer diameter of the vessel.
[00373] VII.C. As an optional feature of any of the foregoing embodiments the bending radius at the central axis is not more than 90 times as great as, or not more than 80 times as great as, or not more than 70 times as great as, or not more than 60 times as great as, or not more than 50 times as great as, or not more than 40 times as great as, or not more than 30 times as great as, or not more than 20 times as great as, or not more than 10 times as great as, or not more than 9 times as great as, or not more than 8 times as great as, or not more than 7 times as great as, or not more than 6 times as great as, or not more than 5 times as great as, or not more than 4 times as great as, or not more than 3 times as great as, or not more than 2 times as great as, or not more than, the outer diameter of the vessel.
[00374] VII.C. As an optional feature of any of the foregoing embodiments the vessel wall can be a fluid-contacting contact surface made of flexible material. [00375] VII.C. As an optional feature of any of the foregoing embodiments the vessel lumen can be the fluid flow passage of a pump.
[00376] VII.C. As an optional feature of any of the foregoing embodiments the vessel can be a blood bag adapted to maintain blood in good condition for medical use.
[00377] VII.C, VII.D. As an optional feature of any of the foregoing embodiments the polymeric material can be a silicone elastomer or a thermoplastic polyurethane, as two examples, or any material suitable for contact with blood, or with insulin.
[00378] VII.C, VII.D. In an optional embodiment, the vessel has an inner diameter of at least 2 mm, or at least 4 mm.
[00379] VII.C. As an optional feature of any of the foregoing embodiments the vessel is a tube.
[00380] VII.C. As an optional feature of any of the foregoing embodiments the lumen has at least two open ends.
VII.C.l. Vessel Containing Viable Blood, Having a Coating Deposited from an
Organosilicon Precursor
[00381] VII.C.l. Even another embodiment is a blood containing vessel. Several non-limiting examples of such a vessel are a blood transfusion bag, a blood sample collection vessel in which a sample has been collected, the tubing of a heart-lung machine, a flexible-walled blood collection bag, or tubing used to collect a patient' s blood during surgery and reintroduce the blood into the patient's vasculature. If the vessel includes a pump for pumping blood, a particularly suitable pump is a centrifugal pump or a peristaltic pump. The vessel has a wall; the wall has an inner contact surface defining a lumen. The inner contact surface of the wall has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section. The coating can be as thin as monomolecular thickness or as thick as about 1000 nm. The vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
[00382] VII.C.l. An embodiment is a blood containing vessel including a wall and having an inner contact surface defining a lumen. The inner contact surface has an at least partial coating of a hydrophobic layer. The coating can also comprise or consist essentially of SiOx, where x is as defined in this specification. The thickness of the coating is within the range from monomolecular thickness to about 1000 nm thick on the inner contact surface. The vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
VII.C.2. Coating Deposited from an Organosilicon Precursor Reduces Clotting or platelet activation of Blood in the Vessel
[00383] VII.C.2. Another embodiment is a vessel having a wall. The wall has an inner contact surface defining a lumen and has an at least partial coating of a hydrophobic layer, where optionally w, x, y, and z are as previously defined in the Definition Section. The thickness of the coating is from monomolecular thickness to about 1000 nm thick on the inner contact surface. The coating is effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface, compared to the same type of wall uncoated with a hydrophobic layer.
[00384] VII.C.2. It is contemplated that the incorporation of a hydrophobic layer will reduce the adhesion or clot forming tendency of the blood, as compared to its properties in contact with an unmodified polymeric or SiOx contact surface. This property is contemplated to reduce or potentially eliminate the need for treating the blood with heparin, as by reducing the necessary blood concentration of heparin in a patient undergoing surgery of a type requiring blood to be removed from the patient and then returned to the patient, as when using a heart-lung machine during cardiac surgery. It is contemplated that this will reduce the complications of surgery involving the passage of blood through such a vessel, by reducing the bleeding complications resulting from the use of heparin.
[00385] VII.C.2. Another embodiment is a vessel including a wall and having an inner contact surface defining a lumen. The inner contact surface has an at least partial coating of a hydrophobic layer, the thickness of the coating being from monomolecular thickness to about 1000 nm thick on the inner contact surface, the coating being effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface.
VII.C.3. Vessel Containing Viable Blood, Having a Coating of Group III or IV Element
[00386] VII.C.3. Another embodiment is a blood containing vessel having a wall having an inner contact surface defining a lumen. The inner contact surface has an at least partial coating of a composition comprising one or more elements of Group III, one or more elements of Group IV , or a combination of two or more of these. The thickness of the coating is between monomolecular thickness and about 1000 nm thick, inclusive, on the inner contact surface. The vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
VII.C.4. Coating of Group III or IV Element Reduces Clotting or Platelet Activation of Blood in the Vessel
[00387] VII.C.4. Optionally, in the vessel of the preceding paragraph, the coating of the Group III or IV Element is effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface of the vessel wall.
VII.D. Pharmaceutical Delivery Vessels
[00388] VII.D. A coated vessel or container as described herein can be used for preventing or reducing the escape of a compound or composition contained in the vessel into the environment surrounding the vessel.
[00389] Further uses of the coating and vessel as described herein, which are apparent from any part of the description and claims, are also contemplated.
VII.D.l. Vessel Containing Insulin, Having a Coating Deposited from an
Organosilicon Precursor
[00390] VII.D. l. Another embodiment is an insulin containing vessel including a wall having an inner contact surface defining a lumen. The inner contact surface has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section. The coating can be from monomolecular thickness to about 1000 nm thick on the inner contact surface.
Insulin is disposed within the lumen in contact with the SiwOxCyHz coating.
[00391] VII.D. l. Still another embodiment is an insulin containing vessel including a wall and having an inner contact surface defining a lumen. The inner contact surface has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section, the thickness of the coating being from monomolecular thickness to about 1000 nm thick on the inner contact surface. Insulin, for example pharmaceutical insulin FDA approved for human use, is disposed within the lumen in contact with the hydrophobic layer. [00392] VII.D.1. It is contemplated that the incorporation of a hydrophobic layer, characterized as defined in the Definition Section, will reduce the adhesion or precipitation forming tendency of the insulin in a delivery tube of an insulin pump, as compared to its properties in contact with an unmodified polymeric contact surface. This property is
contemplated to reduce or potentially eliminate the need for filtering the insulin passing through the delivery tube to remove a solid precipitate.
VII.D.2. Coating Deposited from an Organosilicon Precursor Reduces Precipitation of Insulin in the Vessel
[00393] VII.D.2. Optionally, in the vessel of the preceding paragraph, the coating of a hydrophobic layer is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface, compared to the same contact surface absent the hydrophobic layer.
[00394] VII.D.2. Even another embodiment is a vessel again comprising a wall and having an inner contact surface defining a lumen. The inner contact surface includes an at least partial coating of a hydrophobic layer. The thickness of the coating is in the range from monomolecular thickness to about 1000 nm thick on the inner contact surface. The coating is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface.
VII.D.3. Vessel Containing Insulin, Having a Coating of Group III or IV Element
[00395] VII.D.3. Another embodiment is an insulin containing vessel including a wall having an inner contact surface defining a lumen. The inner contact surface has an at least partial coating of a composition comprising carbon, one or more elements of Group III, one or more elements of Group IV, or a combination of two or more of these. The coating can be from monomolecular thickness to about 1000 nm thick on the inner contact surface. Insulin is disposed within the lumen in contact with the coating.
VII.D.4. Coating of Group III or IV Element Reduces Precipitation of Insulin in the
Vessel
[00396] VII.D.4. Optionally, in the vessel of the preceding paragraph, the coating of a composition comprising carbon, one or more elements of Group III, one or more elements of Group IV, or a combination of two or more of these, is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface, compared to the same contact surface absent the coating. Antimicrobial Treatment
[00397] After a first treatment of SiOx, SiOxCy, or SiNxCy is applied to the contact surface as described above, a second antimicrobially effective treatment is applied to the contact surface with its first treatment. The second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment. One particularly contemplated
antimicrobial agent is silver or a silver compound.
[00398] Suitable antimicrobial treatments include the following.
Traditional Coating Technologies
[00399] For this method, a silver ion coating is applied by dip or paint to inhibit infections in invasive medical devices and to create burn and wound treatments. The device must be properly prepared first through sterilization and removal of debris before any coating process is performed. This traditional coating method has worked well, and several companies have proprietary application methods using nano-sized silver crystals for wound treatments. Devices and wound dressings treated with silver must be able to withstand the high heat associated with coating technologies. For example, certain coating technologies, such as plating, could not be used to apply silver oxide to a gauze bandage or disposable diaper-the fabric would disintegrate.
[00400] Another difficulty is observed when silver is used in conjunction with certain surfaces or coatings. For example, many medical devices, such as catheters, are manufactured with a hydrophobic polymer matrix, which limits the silver ion concentration near the device surface. Silver oxide requires the presence of moisture to release its anti-microbial properties. Affixing silver oxide to a hydrophobic polymer reduces the moisture present and thus decreases silver's antimicrobial effect. Commercially available devices coated with these processes may experience limited effectiveness.
Modified Compound Polymers.
[00401] Manufacturers are also working to extend silver antimicrobial effectiveness through modified compound polymers. Products called silver-antimicrobial compounds address this problem by adding silver mixed with a ceramic, such as zirconium phosphate, directly into the polymer material before it is manufactured into a medical device. For the present purposes, incorporation of the antimicrobial material into the polymer from which the contact surface is made is regarded as an antimicrobial treatment of the surface.
[00402] These so-called iontophoric polymers are designed to release silver ions when wet with body fluids. When the composite material comes in contact with or is immersed in an electrolytic fluid (such as saline, blood, drug preparations, or urine) the metal powders become a mass of tiny electrodes. Each molecule becomes an anode or a cathode, making the polymer conductive, which causes it to release the silver ions. The ion exchange is a slow process, which is a benefit because it may extend the antimicrobial effect.8 This application technique has been used in catheters. Other uses being explored include orthopedic implants, pacemaker leads, suture leads, and feeding tubes.
Ordered Nanostructures
[00403] The newest innovation for silver oxide antimicrobials involves surface-engineered ordered nanostructures of silver oxide that are built on the medical device surface. The approach employs nanotechnology to apply antimicrobial silver to medical devices. Nanotechnology may provide the most effective platform to maximize the antimicrobial capability of silver. The nanostructures comprise silver particles. Because each tiny particle in a nanostmcture has its own surface area, it increases the overall surface area of the silver oxide. A larger surface area means more silver can interact with body fluids to encounter and inhibit microbes. Surface engineering of ordered nanostructures takes place on the nanometer scale.
[00404] One way to process nano-sized silver particles is through ionic plasma deposition (IPD) processing. Broadly speaking, IPD works with molecules smaller than 100 nanometers. The process creates a surface-engineered ordered silver nanostmcture by first creating a vacuum to remove all contaminants. High kinetic energies that average 200 eV guide the charged silver ions or plasma to the surface of the medical device. The process mns at ambient temperature and can be supercooled when required, enabling a wide choice of materials. Temperature-sensitive materials such as gauze, paper, plastics, and synthetic fibers can be treated with the silver process. The thermodynamic effects that are often associated with poor adhesion are controlled in the plasma rather than on the substrate. Depositing material ions are accelerated to ensure that the depositing species are the correct energy for the desired process and for the medical device polymer material. This allows for a broad range of custom stoichiometries and demonstrates that IPD technology is adaptable when used to treat medical polymers. Low-temperature polymers are used in soft-tissue implants. These polymers, such as polyethylene, polyester, polypropylene, and even Teflon (PTFE), can be treated with IPD nanotechnology.
[00405] IPD can be controlled for particle size, density, and rate of deposition. Because it incorporates a high degree of control and low heat application, IPD also has traits of adhesion and repeatability for silver application. The structures are laid down in a highly ordered surface. Deposition is possible in concentric plasma to almost any length. Source-material use is very efficient, so that high- volume precious-metal applications such as silver, platinum, and gold are economical.
[00406] Silver oxide application should maintain conformal quality of the medical device surface regardless of surface morphology. During the IPD process, the silver is deposited into blind holes, vias, and cavities with aspect ratios of 5: 1. Coatings are now measured in angstroms, and application layers must be extremely thin.9 IPD surface-engineered
nanotechnology has ultra-thin-film capability, which can be used to treat flexible, porous materials such as antimicrobial bandages.
[00407] Many healthcare-acquired infections are the result of pathogens that are resistant to antibodies. The nature of silver and its antimicrobial effects make it an attractive material for medical device use. A number of options are available for applying silver antimicrobial technologies. Application processes continue to become more sophisticated, enabling optimal ion release and longer-lasting effects.
[00408] As another example of antimicrobial treatment, silver ions can be incorporated in carrier particles - like zeolites - which can then be applied to the contact surface, preferably after it is treated by PECVD to provide a functional coating.
[00409] As still another example of antimicrobial treatment, nanoparticles or ions of silver can be entrained in an airstream, conveyed into plasma enhanced chemical vapor deposition or similar apparatus, and driven into the contact surface or a surface coating on the contact surface, as by applying a DC bias to an electrode behind the contact surface relative to the source of nanoparticles. [00410] The invention is believed to function as follows, although this theory of operation does not limit the invention, and any inaccuracy of this theory does not change the scope of the invention. Silver ions are believed to work at the surface of a product through the controlled release of silver ions which attack microbes and inhibit their growth. The silver ions exchange with other positive ions (often sodium) from the moisture in the environment, effecting a release of silver "on demand". Silver ions are randomly oriented and distributed through the surface of a fiber, polymer or coating. In conditions that support bacterial growth, positive ions, in ambient moisture, exchange with silver ions. The exchanged silver ions are now available to control microbial growth. Silver ions attack multiple targets in the microbe to prevent it from growing to a destructive population. They are believed to fight cell growth in three ways:
1.Prevents respiration by inhibiting transport functions in the cell wall
2. Inhibits cell division (reproduction)
3. Disrupts cell metabolism
WORKING EXAMPLES
Example 0: Basic Protocols for Forming and Coating Tubes and Syringe Barrels
[00411] The vessels tested in the subsequent working examples were formed and coated according to the following exemplary protocols, except as otherwise indicated in individual examples. Particular parameter values given in the following basic protocols, e.g. the electric power and process gas flow, are typical values. Whenever parameter values were changed in comparison to these typical values, this will be indicated in the subsequent working examples. The same applies to the type and composition of the process gas.
Protocol for Forming COC Tube (used, e.g., in Examples 1, 19)
[00412] Cyclic olefin copolymer (COC) tubes of the shape and size commonly used as evacuated blood collection tubes ("COC tubes") were injection molded from Topas® 8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG, Frankfurt am Main, Germany, having these dimensions: 75 mm length, 13 mm outer diameter, and 0.85 mm wall thickness, each having a volume of about 7.25 cm and a closed, rounded end. Protocol for Forming PET Tube (used, e.g., in Examples 2, 4, 8, 9, 10)
[00413] Polyethylene terephthalate (PET) tubes of the type commonly used as evacuated blood collection tubes ("PET tubes") were injection molded in the same mold used for the Protocol for Forming COC Tube, having these dimensions: 75 mm length, 13 mm outer diameter, and 0.85 mm wall thickness, each having a volume of about 7.25 cm and a closed, rounded end.
Protocol for Coating Tube Interior with SiOx
(used, e.g., in Examples 1, 2, 4, 8, 9, 10, 18, 19)
[00414] The apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45, which is a specific contemplated embodiment, was used. The vessel holder 50 was made from Delrin® acetal resin, available from E.I. du Pont de Nemours and Co., Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode (160).
[00415] The electrode 160 was made from copper with a Delrin® shield. The Delrin® shield was conformal around the outside of the copper electrode 160. The electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
[00416] The tube used as the vessel 80 was inserted into the vessel holder 50 base sealing with Viton® O-rings 490, 504 (Viton® is a trademark of DuPont Performance Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube (FIG. 45). The tube 80 was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
[00417] The copper plasma screen 610 was a perforated copper foil material (K&S
Engineering, Chicago Illinois, USA, Part #LXMUW5 copper mesh) cut to fit the outside diameter of the tube, and was held in place by a radially extending abutment contact surface 494 that acted as a stop for the tube insertion (see FIG. 45). Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108, insuring good electrical contact. [00418] The brass probe or counter electrode 108 extended approximately 70 mm into the interior of the tube and had an array of #80 wire (diameter = 0.0135 inch or 0.343 mm). The brass probe or counter electrode 108 extended through a Swagelok® fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure. The brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
[00419] The gas delivery port 110 was 12 holes in the probe or counter electrode 108 along the length of the tube (three on each of four sides oriented 90 degrees from each other) and two holes in the aluminum cap that plugged the end of the gas delivery port 110. The gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line. In addition, the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the tube.
[00420] The gas system was comprised of a Aalborg® GFC17 mass flow meter (Part # EW- 32661-34, Cole-Parmer Instrument Co., Barrington Illinois USA) for controllably flowing oxygen at 90 seem (or at the specific flow reported for a particular example) into the process and a polyether ether ketone ("PEEK") capillary (outside diameter, "OD" 1/16-inch (1.5-mm.), inside diameter, "ID" 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m). The PEEK capillary end was inserted into liquid hexamethyldisiloxane ("HMDSO," Alfa Aesar® Part Number L16970, NMR Grade, available from Johnson Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to the lower pressure in the tube during processing. The HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
[00421] To ensure no condensation of the liquid HMDSO past this point, the gas stream (including the oxygen) was diverted to the pumping line when it was not flowing into the interior of the tube for processing via a Swagelok® 3-way valve. Once the tube was installed, the vacuum pump valve was opened to the vessel holder 50 and the interior of the tube. [00422] An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system. The pumping system allowed the interior of the tube to be reduced to pressure(s) of less than 200 mTorr while the process gases were flowing at the indicated rates.
[00423] Once the base vacuum level was achieved, the vessel holder 50 assembly was moved into the electrode 160 assembly. The gas stream (oxygen and HMDSO vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3- way valve from the pumping line to the gas delivery port 110). Pressure inside the tube was approximately 300 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum. In addition to the tube pressure, the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
[00424] Once the gas was flowing to the interior of the tube, the RF power supply was turned on to its fixed power level. A ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 50 Watts. The output power was calibrated in this and all following Protocols and Examples using a Bird Corporation Model 43 RF Watt meter connected to the RF output of the power supply during operation of the coating apparatus. The following relationship was found between the dial setting on the power supply and the output power: RF Power Out = 55 x Dial Setting. In the priority applications to the present application, a factor 100 was used, which was incorrect. The RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the tube) to the 50 ohm output impedance of the ENI ACG-6 RF power supply. The forward power was 50 Watts (or the specific amount reported for a particular example) and the reflected power was 0 Watts so that the applied power was delivered to the interior of the tube. The RF power supply was controlled by a laboratory timer and the power on time set to 5 seconds (or the specific time period reported for a particular example). Upon initiation of the RF power, a uniform plasma was established inside the interior of the tube. The plasma was maintained for the entire 5 seconds until the RF power was terminated by the timer. The plasma produced a silicon oxide coating of approximately 20 nm thickness (or the specific thickness reported in a particular example) on the interior of the tube contact surface. [00425] After coating, the gas flow was diverted back to the vacuum line and the vacuum valve was closed. The vent valve was then opened, returning the interior of the tube to atmospheric pressure (approximately 760 Torr). The tube was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
Protocol for Coating Tube Interior with Hydrophobic layer
(used, e.g., in Example 9)
[00426] The apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45, which is a specific contemplated embodiment, was used. The vessel holder 50 was made from Delrin® acetal resin, available from E.I. du Pont de Nemours and Co., Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode (160).
[00427] The electrode 160 was made from copper with a Delrin® shield. The Delrin® shield was conformal around the outside of the copper electrode 160. The electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
[00428] The tube used as the vessel 80 was inserted into the vessel holder 50 base sealing with Viton® O-rings 490, 504 (Viton® is a trademark of DuPont Performance Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube (FIG. 45). The tube 80 was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
[00429] The copper plasma screen 610 was a perforated copper foil material (K&S
Engineering, Chicago Illinois, USA, Part #LXMUW5 copper mesh) cut to fit the outside diameter of the tube, and was held in place by a radially extending abutment contact surface 494 that acted as a stop for the tube insertion (see FIG. 45). Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108, insuring good electrical contact.
[00430] The brass probe or counter electrode 108 extended approximately 70 mm into the interior of the tube and had an array of #80 wire (diameter = 0.0135 inch or 0.343 mm). The brass probe or counter electrode 108 extended through a Swagelok® fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure. The brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
[00431] The gas delivery port 110 was 12 holes in the probe or counter electrode 108 along the length of the tube (three on each of four sides oriented 90 degrees from each other) and two holes in the aluminum cap that plugged the end of the gas delivery port 110. The gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line. In addition, the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the tube.
[00432] The gas system was comprised of a Aalborg® GFC17 mass flow meter (Part # EW- 32661-34, Cole-Parmer Instrument Co., Barrington Illinois USA) for controllably flowing oxygen at 60 seem (or at the specific flow reported for a particular example) into the process and a polyether ether ketone ("PEEK") capillary (outside diameter, "OD" 1/16-inch (1.5-mm.), inside diameter, "ID" 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m). The PEEK capillary end was inserted into liquid hexamethyldisiloxane ("HMDSO," Alfa Aesar® Part Number L16970, NMR Grade, available from Johnson Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to the lower pressure in the tube during processing. The HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
[00433] To ensure no condensation of the liquid HMDSO past this point, the gas stream (including the oxygen) was diverted to the pumping line when it was not flowing into the interior of the tube for processing via a Swagelok® 3-way valve. Once the tube was installed, the vacuum pump valve was opened to the vessel holder 50 and the interior of the tube.
[00434] An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system. The pumping system allowed the interior of the tube to be reduced to pressure(s) of less than 200 mTorr while the process gases were flowing at the indicated rates.
[00435] Once the base vacuum level was achieved, the vessel holder 50 assembly was moved into the electrode 160 assembly. The gas stream (oxygen and HMDSO vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3- way valve from the pumping line to the gas delivery port 110). Pressure inside the tube was approximately 270 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum. In addition to the tube pressure, the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
[00436] Once the gas was flowing to the interior of the tube, the RF power supply was turned on to its fixed power level. A ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 39 Watts. The RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the tube) to the 50 ohm output impedance of the ENI ACG-6 RF power supply. The forward power was 39 Watts (or the specific amount reported for a particular example) and the reflected power was 0 Watts so that the applied power was delivered to the interior of the tube. The RF power supply was controlled by a laboratory timer and the power on time set to 7 seconds (or the specific time period reported for a particular example). Upon initiation of the RF power, a uniform plasma was established inside the interior of the tube. The plasma was maintained for the entire 7 seconds until the RF power was terminated by the timer. The plasma produced a silicon oxide coating of approximately 20 nm thickness (or the specific thickness reported in a particular example) on the interior of the tube contact surface.
[00437] After coating, the gas flow was diverted back to the vacuum line and the vacuum valve was closed. The vent valve was then opened, returning the interior of the tube to atmospheric pressure (approximately 760 Torr). The tube was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
Protocol for Forming COC Syringe Barrel (used, e.g., in Examples 3, 5, 11-18, 20)
[00438] Syringe barrels ("COC syringe barrels"), CV Holdings Part 11447, each having a 2.8 mL overall volume (excluding the Luer fitting) and a nominal 1 mL delivery volume or plunger displacement, Luer adapter type, were injection molded from Topas® 8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG, Frankfurt am Main, Germany, having these dimensions: about 51 mm overall length, 8.6 mm inner syringe barrel diameter and 1.27 mm wall thickness at the cylindrical portion, with an integral 9.5 millimeter length needle capillary Luer adapter molded on one end and two finger flanges molded near the other end.
Protocol for Coating COC Syringe Barrel Interior with SiOx
(used, e.g. in Examples 3, 5, 18)
[00439] An injection molded COC syringe barrel was interior coated with SiOx. The apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45 was modified to hold a COC syringe barrel with butt sealing at the base of the COC syringe barrel. Additionally a cap was fabricated out of a stainless steel Luer fitting and a polypropylene cap that sealed the end of the COC syringe barrel (illustrated in FIG. 26), allowing the interior of the COC syringe barrel to be evacuated.
[00440] The vessel holder 50 was made from Delrin® with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode 160.
[00441] The electrode 160 was made from copper with a Delrin® shield. The Delrin® shield was conformal around the outside of the copper electrode 160. The electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide. The COC syringe barrel was inserted into the vessel holder 50, base sealing with an Viton® O- rings.
[00442] The COC syringe barrel was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen. The copper plasma screen was a perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter of the COC syringe barrel and was held in place by a abutment contact surface 494 that acted as a stop for the COC syringe barrel insertion. Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108 insuring good electrical contact.
[00443] The probe or counter electrode 108 extended approximately 20 mm into the interior of the COC syringe barrel and was open at its end. The brass probe or counter electrode 108 extended through a Swagelok® fitting located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure. The brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
[00444] The gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line. In addition, the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and
hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the COC syringe barrel.
[00445] The gas system was comprised of a Aalborg® GFC17 mass flow meter (Cole Parmer Part # EW-32661-34) for controllably flowing oxygen at 90 seem (or at the specific flow reported for a particular example) into the process and a PEEK capillary (OD 1/16-inch (3-mm) ID 0.004 inches (0.1 mm)) of length 49.5 inches (1.26 m). The PEEK capillary end was inserted into liquid hexamethyldisiloxane (Alfa Aesar® Part Number L16970, NMR Grade). The liquid HMDSO was pulled through the capillary due to the lower pressure in the COC syringe barrel during processing. The HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
[00446] To ensure no condensation of the liquid HMDSO past this point, the gas stream (including the oxygen) was diverted to the pumping line when it was not flowing into the interior of the COC syringe barrel for processing via a Swagelok® 3-way valve.
[00447] Once the COC syringe barrel was installed, the vacuum pump valve was opened to the vessel holder 50 and the interior of the COC syringe barrel. An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system. The pumping system allowed the interior of the COC syringe barrel to be reduced to pressure(s) of less than 150 mTorr while the process gases were flowing at the indicated rates. A lower pumping pressure was achievable with the COC syringe barrel, as opposed to the tube, because the COC syringe barrel has a much smaller internal volume.
[00448] After the base vacuum level was achieved, the vessel holder 50 assembly was moved into the electrode 160 assembly. The gas stream (oxygen and HMDSO vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3-way valve from the pumping line to the gas delivery port 110). The pressure inside the COC syringe barrel was approximately 200 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum. In addition to the COC syringe barrel pressure, the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
[00449] When the gas was flowing to the interior of the COC syringe barrel, the RF power supply was turned on to its fixed power level. A ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 30 Watts. The RF power supply was connected to a COMDEL CPMX1000 auto match that matched the complex impedance of the plasma (to be created in the COC syringe barrel) to the 50 ohm output impedance of the ENI ACG-6 RF power supply. The forward power was 30 Watts (or whatever value is reported in a working example) and the reflected power was 0 Watts so that the power was delivered to the interior of the COC syringe barrel. The RF power supply was controlled by a laboratory timer and the power on time set to 5 seconds (or the specific time period reported for a particular example).
[00450] Upon initiation of the RF power, a uniform plasma was established inside the interior of the COC syringe barrel. The plasma was maintained for the entire 5 seconds (or other coating time indicated in a specific example) until the RF power was terminated by the timer. The plasma produced a silicon oxide coating of approximately 20 nm thickness (or the thickness reported in a specific example) on the interior of the COC syringe barrel contact surface.
[00451] After coating, the gas flow was diverted back to the vacuum line and the vacuum valve was closed. The vent valve was then opened, returning the interior of the COC syringe barrel to atmospheric pressure (approximately 760 Torr). The COC syringe barrel was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer (used, e.g., in Examples 11, 12, 15-18, 20)
[00452] COC syringe barrels as previously identified were interior coated with a lubricity layer. The apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45 was modified to hold a COC syringe barrel with butt sealing at the base of the COC syringe barrel. Additionally a cap was fabricated out of a stainless steel Luer fitting and a polypropylene cap that sealed the end of the COC syringe barrel (illustrated in FIG. 26). The installation of a Buna-N O-ring onto the Luer fitting allowed a vacuum tight seal, allowing the interior of the COC syringe barrel to be evacuated.
[00453] The vessel holder 50 was made from Delrin® with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode 160.
[00454] The electrode 160 was made from copper with a Delrin® shield. The Delrin® shield was conformal around the outside of the copper electrode 160. The electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide. The COC syringe barrel was inserted into the vessel holder 50, base sealing with Viton® O-rings around the bottom of the finger flanges and lip of the COC syringe barrel.
[00455] The COC syringe barrel was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen. The copper plasma screen was a perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter of the COC syringe barrel and was held in place by a abutment contact surface 494 that acted as a stop for the COC syringe barrel insertion. Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108 insuring good electrical contact.
[00456] The probe or counter electrode 108 extended approximately 20mm (unless otherwise indicated) into the interior of the COC syringe barrel and was open at its end. The brass probe or counter electrode 108 extended through a Swagelok® fitting located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure. The brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
[00457] The gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line. In addition, the gas system was connected to the gas delivery port 110 allowing the process gas,
octamethylcyclotetrasiloxane (OMCTS) (or the specific process gas reported for a particular example) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the COC syringe barrel.
[00458] The gas system was comprised of a commercially available Horiba VC1310/SEF8240 OMCTS 10SC 4CR heated mass flow vaporization system that heated the OMCTS to about 100°C. The Horiba system was connected to liquid octamethylcyclotetrasiloxane (Alfa Aesar® Part Number A12540, 98%) through a 1/8-inch (3-mm) outside diameter PFA tube with an inside diameter of 1/16 in (1.5 mm). The OMCTS flow rate was set to 1.25 seem (or the specific organosilicon precursor flow reported for a particular example). To ensure no condensation of the vaporized OMCTS flow past this point, the gas stream was diverted to the pumping line when it was not flowing into the interior of the COC syringe barrel for processing via a Swagelok® 3-way valve.
[00459] Once the COC syringe barrel was installed, the vacuum pump valve was opened to the vessel holder 50 and the interior of the COC syringe barrel. An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system. The pumping system allowed the interior of the COC syringe barrel to be reduced to pressure(s) of less than 100 mTorr while the process gases were flowing at the indicated rates. A lower pressure could be obtained in this instance, compared to the tube and previous COC syringe barrel examples, because the overall process gas flow rate is lower in this instance.
[00460] Once the base vacuum level was achieved, the vessel holder 50 assembly was moved into the electrode 160 assembly. The gas stream (OMCTS vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3-way valve from the pumping line to the gas delivery port 110). Pressure inside the COC syringe barrel was approximately 140 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum. In addition to the COC syringe barrel pressure, the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 6 Torr.
[00461] Once the gas was flowing to the interior of the COC syringe barrel, the RF power supply was turned on to its fixed power level. A ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 7.5 Watts (or other power level indicated in a specific example). The RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the COC syringe barrel) to the 50 ohm output impedance of the ENI ACG-6 RF power supply. The forward power was 7.5 Watts and the reflected power was 0 Watts so that 7.5 Watts of power (or a different power level delivered in a given example) was delivered to the interior of the COC syringe barrel. The RF power supply was controlled by a laboratory timer and the power on time set to 10 seconds (or a different time stated in a given example).
[00462] Upon initiation of the RF power, a uniform plasma was established inside the interior of the COC syringe barrel. The plasma was maintained for the entire coating time, until the RF power was terminated by the timer. The plasma produced a lubricity layer on the interior of the COC syringe barrel contact surface.
[00463] After coating, the gas flow was diverted back to the vacuum line and the vacuum valve was closed. The vent valve was then opened, returning the interior of the COC syringe barrel to atmospheric pressure (approximately 760 Torr). The COC syringe barrel was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating (used, e.g., in Examples 12, 15, 16, 17)
[00464] The Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer was also used for applying an HMDSO coating, except substituting HMDSO for OMCTS.
Example 1
[00465] V. In the following test, hexamethyldisiloxane (HMDSO) was used as the organosilicon ("O-Si") feed to PECVD apparatus of FIG. 2 to apply an SiOx coating on the internal contact surface of a cyclic olefin copolymer (COC) tube as described in the Protocol for Forming COC Tube. The deposition conditions are summarized in the Protocol for Coating Tube Interior with SiOx and Table 1. The control was the same type of tube to which no barrier coating was applied. The coated and uncoated tubes were then tested for their oxygen transmission rate (OTR) and their water vapor transmission rate (WVTR). [00466] V. Referring to Table 1, the uncoated COC tube had an OTR of 0.215 cc/tube/day. Tubes A and B subjected to PECVD for 14 seconds had an average OTR of 0.0235 cc/tube/day. These results show that the SiOx coating provided an oxygen transmission BIF over the uncoated tube of 9.1. In other words, the SiOx barrier coating reduced the oxygen transmission through the tube to less than one ninth its value without the coating.
[00467] V. Tube C subjected to PECVD for 7 seconds had an OTR of 0.026. This result shows that the SiOx coating provided an OTR BIF over the uncoated tube of 8.3. In other words, the SiOx barrier coating applied in 7 seconds reduced the oxygen transmission through the tube to less than one eighth of its value without the coating.
[00468] V. The relative WVTRs of the same barrier coatings on COC tubes were also measured. The uncoated COC tube had a WVTR of 0.27 mg/tube/day. Tubes A and B subjected to PECVD for 14 seconds had an average WVTR of 0.10 mg/tube/day or less. Tube C subjected to PECVD for 7 seconds had a WVTR of 0.10 mg/tube/day. This result shows that the SiOx coating provided a water vapor transmission barrier improvement factor (WVTR BIF) over the uncoated tube of about 2.7. This was a surprising result, since the uncoated COC tube already has a very low WVTR.
Example 2
[00469] V. A series of PET tubes, made according to the Protocol for Forming PET Tube, were coated with SiOx according to the Protocol for Coating Tube Interior with SiOx under the conditions reported in Table 2. Controls were made according to the Protocol for Forming PET Tube, but left uncoated. OTR and WVTR samples of the tubes were prepared by epoxy-sealing the open end of each tube to an aluminum adaptor.
[00470] V. In a separate test, using the same type of coated PET tubes, mechanical scratches of various lengths were induced with a steel needle through the interior coating, and the OTR BIF was tested. Controls were either left uncoated or were the same type of coated tube without an induced scratch. The OTR BIF, while diminished, was still improved over uncoated tubes (Table 2A). [00471] V. Tubes were tested for OTR as follows. Each sample/adaptor assembly was fitted onto a MOCON® Oxtran 2/21 Oxygen Permeability Instrument. Samples were allowed to equilibrate to transmission rate steady state (1-3 days) under the following test conditions:
• Test Gas: Oxygen
• Test Gas Concentration: 100%
• Test Gas Humidity: 0% relative humidity
• Test Gas Pressure: 760 mmHg
• Test Temperature: 23.0°C (73.4°F)
• Carrier Gas: 98% nitrogen, 2% hydrogen
• Carrier Gas Humidity: 0% relative humidity
[00472] V. The OTR is reported as average of two determinations in Table 2.
[00473] V. Tubes were tested for WVTR as follows. The sample/adaptor assembly was fitted onto a MOCON® Permatran- W 3/31 Water Vapor Permeability Instrument. Samples were allowed to equilibrate to transmission rate steady state (1-3 days) under the following test conditions:
• Test Gas: Water Vapor
• Test Gas Concentration: NA
• Test Gas Humidity: 100% relative humidity
• Test Gas Temperature: 37.8(°C) 100.0(°F)
• Carrier Gas: Dry nitrogen
• Carrier Gas Humidity: 0% relative humidity
[00474] V. The WVTR is reported as average of two determinations in Table 2.
Example 3
[00475] A series of syringe barrels were made according to the Protocol for Forming COC Syringe barrel. The syringe barrels were either barrier coated with SiOx or not under the conditions reported in the Protocol for Coating COC Syringe barrel Interior with SiOx modified as indicated in Table 3.
[00476] OTR and WVTR samples of the syringe barrels were prepared by epoxy- sealing the open end of each syringe barrel to an aluminum adaptor. Additionally, the syringe barrel capillary ends were sealed with epoxy. The syringe-adapter assemblies were tested for OTR or WVTR in the same manner as the PET tube samples, again using a MOCON® Oxtran 2/21 Oxygen Permeability Instrument and a MOCON® Permatran- W 3/31 Water Vapor Permeability Instrument. The results are reported in Table 3.
Example 4
Composition Measurement of Plasma Coatings using X-Ray Photoelectron Spectroscopy (XPS) / Electron Spectroscopy for Chemical Analysis (ESCA) Contact surface Analysis
[00477] V.A. PET tubes made according to the Protocol for Forming PET Tube and coated according to the Protocol for Coating Tube Interior with SiOx were cut in half to expose the inner tube contact surface, which was then analyzed using X-ray photoelectron spectroscopy (XPS).
[00478] V.A. The XPS data was quantified using relative sensitivity factors and a model which assumes a homogeneous layer. The analysis volume is the product of the analysis area (spot size or aperture size) and the depth of information. Photoelectrons are generated within the X-ray penetration depth (typically many microns), but only the photoelectrons within the top three photoelectron escape depths are detected. Escape depths are on the order of 15-35 A, which leads to an analysis depth of -50-100 A. Typically, 95% of the signal originates from within this depth.
[00479] V.A. Table 5 provides the atomic ratios of the elements detected. The analytical parameters used in for XPS are as follows:
Instrument PHI Quantum 2000
-ray source Monochromated Alka 1486.6eV
Acceptance Angle ±23°
Take-off angle 45° Analysis area 600μηι
Charge Correction Cls 284.8 eV
Ion Gun Conditions Ar+, 1 keV, 2 x 2 mm raster
Sputter Rate 15.6 A/min (Si02 Equivalent)
[00480] V.A. XPS does not detect hydrogen or helium. Values given are normalized to Si = 1 for the experimental number (last row) using the elements detected, and to O = 1 for the uncoated polyethylene terephthalate calculation and example. Detection limits are
approximately 0.05 to 1.0 atomic percent. Values given are alternatively normalized to 100% Si + O + C atoms.
[00481] V.A. The Inventive Example has an Si/O ratio of 2.4 indicating an SiOx composition, with some residual carbon from incomplete oxidation of the coating. This analysis demonstrates the composition of an SiOx barrier layer applied to a polyethylene terephthalate tube according to the present invention.
[00482] V.A. Table 4 shows the thickness of the SiOx samples, determined using TEM according to the following method. Samples were prepared for Focused Ion Beam (FIB) cross- sectioning by coating the samples with a sputtered layer of platinum (50-100nm thick) using a K575X Emitech coating system. The coated samples were placed in an FEI FIB200 FIB system. An additional layer of platinum was FIB-deposited by injection of an organo-metallic gas while rastering the 30kV gallium ion beam over the area of interest. The area of interest for each sample was chosen to be a location half way down the length of the tube. Thin cross sections measuring approximately 15μιη ("micrometers") long, 2μιη wide and 15μιη deep were extracted from the die contact surface using a proprietary in-situ FIB lift-out technique. The cross sections were attached to a 200 mesh copper TEM grid using FIB-deposited platinum. One or two windows in each section, measuring about 8μιη wide, were thinned to electron transparency using the gallium ion beam of the FEI FIB.
[00483] V.C. Cross-sectional image analysis of the prepared samples was performed utilizing a Transmission Electron Microscope (TEM). The imaging data was recorded digitally. [00484] The sample grids were transferred to a Hitachi HF2000 transmission electron microscope. Transmitted electron images were acquired at appropriate magnifications. The relevant instrument settings used during image acquisition are given below.
Instrument Transmission Electron
Microscope
Manufacturer/Model Hitachi HF2000
Accelerating Voltage 200 kV
Condenser Lens 1 0.78
Condenser Lens 2 0
Objective Lens 6.34
Condenser Lens Aperture #1
Objective Lens Aperture for #3
imaging
Selective Area Aperture for SAD N/A
Example 5
Plasma Uniformity
[00485] V.A. COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were treated using the Protocol for Coating COC Syringe Barrel Interior with SiOx> with the following variations. Three different modes of plasma generation were tested for coating syringe barrels such as 250 with SiOx films. V.A. In Mode 1, hollow cathode plasma ignition was generated in the gas inlet 310, restricted area 292 and processing vessel lumen 304, and ordinary or non-hollow-cathode plasma was generated in the remainder of the vessel lumen 300.
[00486] V.A. In Mode 2, hollow cathode plasma ignition was generated in the restricted area 292 and processing vessel lumen 304, and ordinary or non-hollow-cathode plasma was generated in the remainder of the vessel lumen 300 and gas inlet 310.
[00487] V.A. In Mode 3, ordinary or non-hollow-cathode plasma was generated in the entire vessel lumen 300 and gas inlet 310. This was accomplished by ramping up power to quench any hollow cathode ignition. Table 6 shows the conditions used to achieve these modes.
[00488] V.A. The syringe barrels 250 were then exposed to a ruthenium oxide staining technique. The stain was made from sodium hypochlorite bleach and Ru(III) chloride hydrate. 0.2g of Ru(EI) chloride hydrate was put into a vial. 10ml bleach were added and mixed thoroughly until the Ru(III) chloride hydrate dissolved.
[00489] V.A. Each syringe barrel was sealed with a plastic Luer seal and 3 drops of the staining mixture were added to each syringe barrel. The syringe barrels were then sealed with aluminum tape and allowed to sit for 30-40 minutes. In each set of syringe barrels tested, at least one uncoated syringe barrel was stained. The syringe barrels were stored with the restricted area 292 facing up.
[00490] V.A. Based on the staining, the following conclusions were drawn:
V.A. 1. The stain started to attack the uncoated (or poorly coated) areas within 0.25 hours of exposure;
V.A. 2. Ignition in the restricted area 292 resulted in SiOx coating of the restricted area 292;
V.A. 3. The best syringe barrel was produced by the test with no hollow cathode plasma ignition in either the gas inlet 310 or the restricted area 292. Only the restricted opening 294 was stained, most likely due to leaking of the stain; and
V.A. 4. Staining is a good qualitative tool to guide uniformity work.
[00491] V.A. Based on all of the above, we concluded: V.A. 1. Under the conditions of the test, hollow cathode plasma in either the gas inlet 310 or the restricted area 292 led to poor uniformity of the coating; and
V.A. 2. The best uniformity was achieved with no hollow cathode plasma in either the gas inlet 310 or the restricted area 292.
Example 6
Interference Patterns from Reflectance Measurements - Prophetic Example
[00492] VIA. Using a UV- Visible Source (Ocean Optics DH2000-BAL Deuterium
Tungsten 200-1000nm), a fiber optic reflection probe (combination emitter/collector Ocean Optics QR400-7 SR/BX with approximately 3mm probe area), miniature detector (Ocean Optics HR4000CG UV-NIR Spectrometer), and software converting the spectrometer signal to a transmittance/wavelength graph on a laptop computer, an uncoated PET tube Becton Dickinson (Franklin Lakes, New Jersey, USA) Product No. 366703 13x75 mm (no additives) is scanned (with the probe emitting and collecting light radially from the centerline of the tube, thus normal to the coated contact surface) both about the inner circumference of the tube and longitudinally along the inner wall of the tube, with the probe, with no observable interference pattern observed. Then a Becton Dickinson Product No. 366703 13x75 mm (no additives) SiOx plasma- coated BD 366703 tube is coated with a 20 nanometer thick Si02 coating as described in Protocol for Coating Tube Interior with SiOx. This tube is scanned in a similar manner as the uncoated tube. A clear interference pattern is observed with the coated tube, in which certain wavelengths were reinforced and others canceled in a periodic pattern, indicating the presence of a coating on the PET tube.
Example 7
Enhanced Light Transmission from Integrating Sphere Detection
[00493] VIA. The equipment used was a Xenon light source (Ocean Optics HL-2000-HP- FHSA - 20W output Halogen Lamp Source (185-2000nm)), an Integrating Sphere detector (Ocean Optics ISP-80-8-I) machined to accept a PET tube into its interior, and HR2000+ES Enhanced Sensitivity UV.VIS spectrometer, with light transmission source and light
receiver fiber optic sources (QP600-2-UV-VIS - 600um Premium Optical FIBER, UV/VIS, 2m), and signal conversion software (SPECTRASUITE - Cross-platform Spectroscopy
Operating SOFTWARE). An uncoated PET tube made according to the Protocol for Forming PET Tube was inserted onto a TEFZEL Tube Holder (Puck), and inserted into the integrating sphere. With the Spectrasuite software in absorbance mode, the absorption (at 615nm) was set to zero. An SiOx coated tube made according to the Protocol for Forming PET Tube and coated according to the Protocol for Coating Tube Interior with SiOx (except as varied in Table 16) was then mounted on the puck, inserted into the integrating sphere and the absorbance recorded at 615nm wavelength. The data is recorded in Table 16.
[00494] VIA. With the SiOx coated tubes, an increase in absorption relative to the uncoated article was observed; increased coating times resulted in increased absorption. The measurement took less than one second.
[00495] VIA. These spectroscopic methods should not be considered limited by the mode of collection (for example, reflectance vs. transmittance vs. absorbance), the frequency or type of radiation applied, or other parameters.
Example 8
Outgassing Measurement on PET
[00496] VLB. Present FIG. 30, adapted from FIG. 15 of U.S. Patent 6,584,828, is a schematic view of a test set-up that was used in a working example for measuring outgassing through an SiOx barrier coating 348 applied according to the Protocol for Coating Tube Interior with SiOx on the interior of the wall 346 of a PET tube 358 made according to the Protocol for Forming PET Tube seated with a seal 360 on the upstream end of a Micro-Flow Technology measurement cell generally indicated at 362.
[00497] VLB. A vacuum pump 364 was connected to the downstream end of a commercially available measurement cell 362 (an Intelligent Gas Leak System with Leak Test Instrument Model ME2, with second generation IMFS sensor, (ΙΟμ/min full range), Absolute Pressure Sensor range: 0-10 Torr, Flow measurement uncertainty: +/- 5% of reading, at calibrated range, employing the Leak-Tek Program for automatic data acquisition (with PC) and signatures/plots of leak flow vs. time. This equipment is supplied by ATC Inc.), and was configured to draw gas from the interior of the PET vessel 358 in the direction of the arrows through the measurement cell 362 for determination of the mass flow rate outgassed vapor into the vessel 358 from its walls.
[00498] VLB. The measurement cell 362 shown and described schematically here was understood to work substantially as follows, though this information might deviate somewhat from the operation of the equipment actually used. The cell 362 has a conical passage 368 through which the outgassed flow is directed. The pressure is tapped at two longitudinally spaced lateral bores 370 and 372 along the passage 368 and fed respectively to the chambers 374 and 376 formed in part by the diaphragms 378 and 380. The pressures accumulated in the respective chambers 374 and 376 deflect the respective diaphragms 378 and 380. These deflections are measured in a suitable manner, as by measuring the change in capacitance between conductive contact surfaces of the diaphragms 378 and 380 and nearby conductive contact surfaces such as 382 and 384. A bypass 386 can optionally be provided to speed up the initial pump-down by bypassing the measurement cell 362 until the desired vacuum level for carrying out the test is reached.
[00499] VLB. The PET walls 350 of the vessels used in this test were on the order of 1 mm thick, and the coating 348 was on the order of 20 nm (nanometers) thick. Thus, the wall 350 to coating 348 thickness ratio was on the order of 50,000 : 1.
[00500] VLB. To determine the flow rate through the measurement cell 362, including the vessel seal 360, 15 glass vessels substantially identical in size and construction to the vessel 358 were successively seated on the vessel seal 360, pumped down to an internal pressure of 1 Torr, then capacitance data was collected with the measurement cell 362 and converted to an
"outgassing" flow rate. The test was carried out two times on each vessel. After the first run, the vacuum was released with nitrogen and the vessels were allowed recovery time to reach equilibrium before proceeding with the second run. Since a glass vessel is believed to have very little outgassing, and is essentially impermeable through its wall, this measurement is understood to be at least predominantly an indication of the amount of leakage of the vessel and connections within the measurement cell 362, and reflects little if any true outgassing or permeation. The results are in Table 7.
[00501] VLB. The family of plots 390 in FIG. 31 shows the "outgas" flow rate, also in micrograms per minute, of individual tubes corresponding to the second run data in previously- mentioned Table 7. Since the flow rates for the plots do not increase substantially with time, and are much lower than the other flow rates shown, the flow rate is attributed to leakage.
[00502] VLB. Table 8 and the family of plots 392 in FIG. 31 show similar data for uncoated tubes made according to the Protocol for Forming PET Tube.
[00503] VLB. This data for uncoated tubes shows much larger flow rates: the increases are attributed to outgas flow of gases captured on or within the inner region of the vessel wall.
There is some spread among the vessels, which is indicative of the sensitivity of the test to small differences among the vessels and/or how they are seated on the test apparatus.
[00504] VLB. Table 9 and the families of plots 394 and 396 in FIG. 31 show similar data for an SiOx barrier coating 348 applied according to the Protocol for Coating PET Tube Interior with SiOx on the interior of the wall 346 of a PET tube made according to the Protocol for Forming PET Tube.
[00505] VLB. The family of curves 394 for the SiOx coated, injection-molded PET tubes of this example shows that the SiOx coating acts as a barrier to limit outgassing from the PET vessel walls, since the flow rate is consistently lower in this test than for the uncoated PET tubes. (The SiOx coating itself is believed to outgas very little.) The separation between the curves 394 for the respective vessels indicates that this test is sensitive enough to distinguish slightly differing barrier efficacy of the SiOx coatings on different tubes. This spread in the family 394 is attributed mainly to variations in gas tightness among the SiOx coatings, as opposed to variations in outgassing among the PET vessel walls or variations in seating integrity (which have a much tighter family 392 of curves). The two curves 396 for samples 2 and 4 are outliers, as demonstrated below, and their disparity from other data is believed to show that the SiOx coatings of these tubes are defective. This shows that the present test can very clearly separate out samples that have been processed differently or damaged.
[00506] VLB. Referring to Tables 8 and 9 previously mentioned and FIG. 32, the data was analyzed statistically to find the mean and the values of the first and third standard deviations above and below the mean (average). These values are plotted in FIG. 32.
[00507] VLB. This statistical analysis first shows that samples 2 and 4 of Table 9
representing coated PET tubes are clear outliers, more than +3 standard deviations away from the mean. These outliers are, however, shown to have some barrier efficacy, as their flow rates are still clearly distinguished from (lower than) those of the uncoated PET tubes.
[00508] VLB. This statistical analysis also shows the power of an outgassing measurement to very quickly and accurately analyze the barrier efficacy of nano-thickness barrier coatings and to distinguish coated tubes from uncoated tubes (which are believed to be indistinguishable using the human senses at the present coating thickness). Referring to FIG. 32, coated PET vessels showing a level of outgassing three standard deviations above the mean, shown in the top group of bars, have less outgassing than uncoated PET vessels showing a level of outgassing three standard deviations below the mean, shown in the bottom group of bars. This data shows no overlap of the data to a level of certainty exceeding 6σ (six-sigma).
[00509] VLB. Based on the success of this test, it is contemplated that the presence or absence of an SiOx coating on these PET vessels can be detected in a much shorter test than this working example, particularly as statistics are generated for a larger number of samples. This is evident, for example from the smooth, clearly separated families of plots even at a time T = 12 seconds for samples of 15 vessels, representing a test duration of about one second following the origin at about T = 11 seconds.
[00510] VLB. It is also contemplated, based on this data, that a barrier efficacy for SiOx coated PET vessels approaching that of glass or equal to glass can be obtained by optimizing the SiOx coating.
Example 9
Wetting Tension - Plasma Coated PET Tube Examples
[00511] VILA.1.a.ii. The wetting tension method is a modification of the method described in ASTM D 2578. Wetting tension is a specific measure for the hydrophobicity or hydrophilicity of a contact surface. This method uses standard wetting tension solutions (called dyne solutions) to determine the solution that comes nearest to wetting a plastic film contact surface for exactly two seconds. This is the film's wetting tension.
[00512] VILA.1.a.ii. The procedure utilized is varied from ASTM D 2578 in that the substrates are not flat plastic films, but are tubes made according to the Protocol for Forming PET Tube and (except for controls) coated according to the Protocol for Coating Tube Interior with Hydrophobic layer. A silicone coated glass syringe (Becton Dickinson Hypak® PRTC glass prefillable syringe with Luer-lok® tip) (1 mL) was also tested. The results of this test are listed in Table 10.
[00513] VH.A. l.a.ii. Surprisingly, plasma coating of uncoated PET tubes (40 dynes/cm) can achieve either higher (more hydrophilic) or lower (more hydrophobic) energy contact surfaces using the same hexamethyldisiloxane (HMDSO) feed gas, by varying the plasma process conditions. A thin (approximately 20-40 nanometers) SiOx coating made according to the Protocol for Coating Tube Interior with SiOx (data not shown in the tables) provides similar wettability as hydrophilic bulk glass substrates. A thin (less than about 100 nanometers) hydrophobic layer made according to the Protocol for Coating Tube Interior with Hydrophobic layer provides similar non- wettability as hydrophobic silicone fluids (data not shown in the tables).
Example 10
Vacuum Retention Study of Tubes Via Accelerated Ageing
[00514] VILA.3 Accelerated ageing offers faster assessment of long term shelf-life products. Accelerated ageing of blood tubes for vacuum retention is described in US Patent 5,792,940, Column 1, Lines 11-49.
[00515] VII.A.3 Three types of polyethylene terephthalate (PET) 13x75 mm (0.85 mm thick walls) molded tubes were tested:
• Becton Dickinson Product No. 366703 13x75 mm (no additives) tube (shelf life 545 days or 18 months), closed with Hemogard® system red stopper and uncolored guard [commercial control] ;
• PET tubes made according to the Protocol for Forming PET Tube, closed with the same type of Hemogard® system red stopper and uncolored guard [internal control]; and
• Injection molded PET 13x75 mm tubes, made according to the Protocol for
Forming PET Tube, coated according to the Protocol for Coating Tube Interior with SiOx, closed with the same type of Hemogard® system red stopper and uncolored guard [inventive sample] . [00516] VILA.3 The BD commercial control was used as received. The internal control and inventive samples were evacuated and capped with the stopper system to provide the desired partial pressure (vacuum) inside the tube after sealing. All samples were placed into a three gallon (3.8 L) 304 SS wide mouth pressure vessel (Sterlitech No. 740340). The pressure vessel was pressurized to 48psi (3.3 atm, 2482 mm.Hg). Water volume draw change determinations were made by (a) removing 3-5 samples at increasing time intervals, (b) permitting water to draw into the evacuated tubes through a 20 gauge blood collection adaptor from a one liter plastic bottle reservoir, (c) and measuring the mass change before and after water draw.
[00517] VII.A.3 Results are indicated on Table 11.
[00518] VII.A.3 The Normalized Average Decay Rate is calculated by dividing the time change in mass by the number of pressurization days and initial mass draw [mass change/(days x initial mass)]. The Accelerated Time to 10% Loss (months) is also calculated. Both data are listed in Table 12.
[00519] VII.A.3 This data indicates that both the commercial control and uncoated internal control have identical vacuum loss rates, and surprisingly, incorporation of a SiOx coating on the PET interior walls improves vacuum retention time by a factor of 2.1.
Example 11
Lubricity layers
[00520] VII.B.l.a. The following materials were used in this test:
• Commercial (BD Hypak® PRTC) glass prefillable syringes with Luer-lok® tip) (ca 1 mL)
• COC syringe barrels made according to the Protocol for Forming COC Syringe barrel;
• Commercial plastic syringe plungers with elastomeric tips taken from Becton Dickinson Product No. 306507 (obtained as saline prefilled syringes);
• Normal saline solution (taken from the Becton-Dickinson Product No. 306507 prefilled syringes);
• Dillon Test Stand with an Advanced Force Gauge (Model AFG-50N)
• Syringe holder and drain jig (fabricated to fit the Dillon Test Stand) [00521] VH.B.l.a. The following procedure was used in this test.
[00522] VH.B.l.a. The jig was installed on the Dillon Test Stand. The platform probe movement was adjusted to 6 in/min (2.5 mm/sec) and upper and lower stop locations were set. The stop locations were verified using an empty syringe and barrel. The commercial saline- filled syringes were labeled, the plungers were removed, and the saline solution was drained via the open ends of the syringe barrels for re-use. Extra plungers were obtained in the same manner for use with the COC and glass barrels.
[00523] VH.B.l.a. Syringe plungers were inserted into the COC syringe barrels so that the second horizontal molding point of each plunger was even with the syringe barrel lip (about 10 mm from the tip end). Using another syringe and needle assembly, the test syringes were filled via the capillary end with 2-3 milliliters of saline solution, with the capillary end uppermost. The sides of the syringe were tapped to remove any large air bubbles at the plunger/ fluid interface and along the walls, and any air bubbles were carefully pushed out of the syringe while maintaining the plunger in its vertical orientation.
[00524] VH.B.l.a. Each filled syringe barrel/plunger assembly was installed into the syringe jig. The test was initiated by pressing the down switch on the test stand to advance the moving metal hammer toward the plunger. When the moving metal hammer was within 5mm of contacting the top of the plunger, the data button on the Dillon module was repeatedly tapped to record the force at the time of each data button depression, from before initial contact with the syringe plunger until the plunger was stopped by contact with the front wall of the syringe barrel.
[00525] VH.B.l.a. All benchmark and coated syringe barrels were run with five replicates (using a new plunger and barrel for each replicate).
[00526] VH.B.l.a. COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were coated with an OMCTS lubricity layer according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer, assembled and filled with saline, and tested as described above in this Example for lubricity layers. The polypropylene chamber used per the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer allowed the OMCTS vapor (and oxygen, if added - see Table 13) to flow through the syringe barrel and through the syringe capillary into the polypropylene chamber (although a lubricity layer can not be needed in the capillary section of the syringe in this instance). Several different coating conditions were tested, as shown in previously mentioned Table 13. All of the depositions were completed on COC syringe barrels from the same production batch.
[00527] The coated samples were then tested using the plunger sliding force test per the protocol of this Example, yielding the results in Table 13, in English and metric force units. The data shows clearly that low power and no oxygen provided the lowest plunger sliding force for COC and coated COC syringes. Note that when oxygen was added at lower power (6 W) (the lower power being a favorable condition) the plunger sliding force increased from 1.09 lb, 0.49 Kg (at Power = 11 W) to 2.27 lb., 1.03 Kg. This indicates that the addition of oxygen can not be desirable to achieve the lowest possible plunger sliding force.
[00528] VH.B.l.a. Note also that the best plunger sliding force (Power = 11 W , plunger sliding force = 1.09 lb, 0.49 Kg) was very near the current industry standard of silicone coated glass (plunger sliding force = 0.58 lb, 0.26 Kg), while avoiding the problems of a glass syringe such as breakability and a more expensive manufacturing process. With additional optimization, values equal to or better than the current glass with silicone performance are expected to be achieved.
[00529] VH.B.l.a. The samples were created by coating COC syringe barrels according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer. An alternative embodiment of the technology herein, would apply the lubricity layer over another thin film coating, such as SiOx, for example applied according to the Protocol for Coating COC Syringe barrel Interior with SiOx.
Example 12
Improved Syringe Barrel Lubricity layer
[00530] VH.B.l.a. The force required to expel a 0.9 percent saline payload from a syringe through a capillary opening using a plastic plunger was determined for inner wall-coated syringes.
[00531] VH.B.l.a. Three types of COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were tested: one type having no internal coating [Uncoated Control], another type with a hexamethyldisiloxane (HMDSO)-based plasma coated internal wall coating [HMDSO Control] according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating, and a third type with an octamethylcyclotetrasiloxane [OMCTS - Inventive Example] -based plasma coated internal wall coating applied according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer. Fresh plastic plungers with elastomeric tips taken from BD Product Becton-Dickinson Product No. 306507 were used for all examples. Saline from Product No. 306507 was also used.
[00532] VH.B.l.a. The plasma coating method and apparatus for coating the syringe barrel inner walls is described in other experimental sections of this application. The specific coating parameters for the HMDSO-based and OMCTS-based coatings are listed in the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating, the Protocol for Coating COC Syringe barrel Interior with OMCTS Lubricity layer, and Table 14.
[00533] VH.B.l.a. The plunger is inserted into the syringe barrel to about 10 millimeters, followed by vertical filling of the experimental syringe through the open syringe capillary with a separate saline-filled syringe/needle system. When the experimental syringe has been filled into the capillary opening, the syringe is tapped to permit any air bubbles adhering to the inner walls to release and rise through the capillary opening.
[00534] VH.B.l.a. The filled experimental syringe barrel/plunger assembly is placed vertically into a home-made hollow metal jig, the syringe assembly being supported on the jig at the finger flanges. The jig has a drain tube at the base and is mounted on Dillon Test Stand with Advanced Force Gauge (Model AFG-50N). The test stand has a metal hammer, moving vertically downward at a rate of six inches (152 millimeters) per minute. The metal hammer contacts the extended plunger expelling the saline solution through the capillary. Once the plunger has contacted the syringe barrel/capillary interface the experiment is stopped.
[00535] VH.B.l.a. During downward movement of the metal hammer/extended plunger, resistance force imparted on the hammer as measured on the Force Gauge is recorded on an electronic spreadsheet. From the spreadsheet data, the maximum force for each experiment is identified.
[00536] VH.B.l.a. Table 14 lists for each Example the Maximum Force average from replicate coated COC syringe barrels and the Normalized Maximum Force as determined by division of the coated syringe barrel Maximum Force average by the uncoated Maximum Force average. [00537] VII.B.1.a. The data indicates all OMCTS-based inner wall plasma coated COC syringe barrels (Inventive Examples C,E,F,G,H) demonstrate much lower plunger sliding force than uncoated COC syringe barrels (uncoated Control Examples A & D) and surprisingly, also much lower plunger sliding force than HMDSO-based inner wall plasma coated COC syringe barrels (HMDSO control Example B). More surprising, an OMCTS-based coating over a silicon oxide (SiOx) gas barrier coating maintains excellent low plunger sliding force (Inventive Example F). The best plunger sliding force was Example C (Power = 8, plunger sliding force = 1.1 lb, 0.5 Kg). It was very near the current industry standard of silicone coated glass (plunger sliding force = 0.58 lb., 0.26 Kg.), while avoiding the problems of a glass syringe such as breakability and a more expensive manufacturing process. With additional optimization, values equal to or better than the current glass with silicone performance are expected to be achieved.
Example 13
Fabrication of COC Syringe Barrel with Exterior Coating - Prophetic Example
[00538] VII.B. I.e. A COC syringe barrel formed according to the Protocol for Forming COC Syringe barrel is sealed at both ends with disposable closures. The capped COC syringe barrel is passed through a bath of Daran® 8100 Saran Latex (Owensboro Specialty Plastics). This latex contains five percent isopropyl alcohol to reduce the contact surface tension of the composition to 32 dynes/cm). The latex composition completely wets the exterior of the COC syringe barrel. After draining for 30 seconds, the coated COC syringe barrel is exposed to a heating schedule comprising 275°F (135°C) for 25 seconds (latex coalescence) and 122°F (50°C) for four hours (finish cure) in respective forced air ovens. The resulting PVdC film is 1/10 mil (2.5 microns) thick. The COC syringe barrel and PVdC-COC laminate COC syringe barrel are measured for OTR and WVTR using a MOCON brand Oxtran 2/21 Oxygen Permeability Instrument and Permatran- W 3/31 Water Vapor Permeability Instrument, respectively.
[00539] VII.B.1 x. Predicted OTR and WVTR values are listed in Table 15, which shows the expected Barrier Improvement Factor (BIF) for the laminate would be 4.3 (OTR-BIF) and 3.0 (WVTR-BIF), respectively. Example 15
Atomic Compositions of PECVD applied OMCTS and HMDSO Coatings
[00540] VII.B.4. COC syringe barrel samples made according to the Protocol for Forming COC Syringe barrel, coated with OMCTS (according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer) or coated with HMDSO according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating were provided. The atomic compositions of the coatings derived from OMCTS or HMDSO were characterized using X-Ray Photoelectron Spectroscopy (XPS).
[00541] VII.B.4. XPS data is quantified using relative sensitivity factors and a model that assumes a homogeneous layer. The analysis volume is the product of the analysis area (spot size or aperture size) and the depth of information. Photoelectrons are generated within the X-ray penetration depth (typically many microns), but only the photoelectrons within the top three photoelectron escape depths are detected. Escape depths are on the order of 15-35 A, which leads to an analysis depth of -50-100 A. Typically, 95% of the signal originates from within this depth.
[00542] VII.B.4. The following analytical parameters were used:
Instrument: PHI Quantum 2000
X-ray source: Monochromated Alka 1486.6eV
Acceptance Angle +23°
Take-off angle 45°
Analysis area 600μιη
Charge Correction Cls 284.8 eV
Ion Gun Conditions Ar+, 1 keV, 2 x 2 mm raster
Sputter Rate 15.6 A/min (SiO2 Equivalent)
[00543] VII.B.4. Table 17 provides the atomic concentrations of the elements detected. XPS does not detect hydrogen or helium. Values given are normalized to 100 percent using the elements detected. Detection limits are approximately 0.05 to 1.0 atomic percent. [00544] VII.B.4. From the coating composition results and calculated starting monomer precursor elemental percent in Table 17, while the carbon atom percent of the HMDSO-based coating is decreased relative to starting HMDSO monomer carbon atom percent (54.1% down to 44.4%), surprisingly the OMCTS-based coating carbon atom percent is increased relative to the OMCTS monomer carbon atom percent (34.8% up to 48.4%), an increase of 39 atomic %, calculated as follows:
100% [(48.4/34.8) - 1] = 39 at.%.
[00545] Also, while the silicon atom percent of the HMDSO-based coating is almost unchanged relative to starting HMDSO monomer silicon atom percent (21.8% to 22.2%), surprisingly the OMCTS-based coating silicon atom percent is significantly decreased relative to the OMCTS monomer silicon atom percent (42.0% down to 23.6%), a decrease of 44 atomic %. With both the carbon and silicon changes, the OMCTS monomer to coating behavior does not trend with that observed in common precursor monomers (e.g. HMDSO). See, e.g., Hans J. Griesser, Ronald C. Chatelier, Chris Martin, Zoran R. Vasic, Thomas R. Gengenbach, George Jessup J. Biomed. Mater. Res. (Appl Biomater) 53: 235-243, 2000.
Example 16
Volatile Components from Plasma Coatings ("Outgassing")
[00546] VII.B.4. COC syringe barrel samples made according to the Protocol for Forming COC Syringe barrel, coated with OMCTS (according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer) or with HMDSO (according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating) were provided. Outgassing gas chromatography/mass spectroscopy (GC/MS) analysis was used to measure the volatile components released from the OMCTS or HMDSO coatings.
[00547] VII.B.4. The syringe barrel samples (four COC syringe barrels cut in half lengthwise) were placed in one of the 1½" (37 mm) diameter chambers of a dynamic headspace sampling system (CDS 8400 auto-sampler). Prior to sample analysis, a system blank was analyzed. The sample was analyzed on an Agilent 7890A Gas Chromatograph/ Agilent 5975 Mass Spectrometer, using the following parameters, producing the data set out in Table 18: • GC Column: 30m X 0.25mm DB-5MS (J&W Scientific),
0.25μιη film thickness
• Flow rate: 1.0 ml/min, constant flow mode
• Detector: Mass Selective Detector (MSD)
Injection Mode: Split injection (10: 1 split ratio)
• Outgassing Conditions: ' (37mm) Chamber, purge for three hour at 85°C, flow 60 ml/min
• Oven temperature: 40°C (5 min.) to 300°C @ 10°C/min.; hold for 5 min. at 300°C.
[00548] The outgassing results from Table 18 clearly indicated a compositional differentiation between the HMDSO-based and OMCTS -based lubricity layers tested. HMDSO-based compositions outgassed trimethylsilanol [(Me)3SiOH] but outgassed no measured higher oligomers containing repeating -(Me)2SiO- moieties, while OMCTS-based compositions outgassed no measured trimethylsilanol [(Me^SiOH] but outgassed higher oligomers containing repeating -(Me)2SiO- moieties. It is contemplated that this test can be useful for differentiating HMDSO-based coatings from OMCTS-based coatings.
[00549] Without limiting the invention according to the scope or accuracy of the following theory, it is contemplated that this result can be explained by considering the cyclic structure of OMCTS, with only two methyl groups bonded to each silicon atom, versus the acyclic structure of HMDSO, in which each silicon atom is bonded to three methyl groups. OMCTS is contemplated to react by ring opening to form a diradical having repeating -(Me)2SiO- moieties which are already oligomers, and can condense to form higher oligomers. HMDSO, on the other hand, is contemplated to react by cleaving at one O-Si bond, leaving one fragment containing a single O-Si bond that recondenses as (Me^SiOH and the other fragment containing no O-Si bond that recondenses as [(Me)3Si]2. [00550] The cyclic nature of OMCTS is believed to result in ring opening and condensation of these ring-opened moieties with outgassing of higher MW oligomers (26 ng/test). In contrast, HMDSO-based coatings are believed not to provide any higher oligomers, based on the relatively low-molecular- weight fragments from HMDSO.
Example 17
Density Determination of Plasma Coatings using X-Ray Reflectivity (XRR)
[00551] VII. B. 4. Sapphire witness samples (0.5 x 0.5 x 0.1 cm) were glued to the inner walls of separate PET tubes, made according to the Protocol for Forming PET tubes. The sapphire witness-containing PET tubes were coated with OMCTS or HMDSO (both according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer, deviating all with 2x power). The coated sapphire samples were then removed and X-ray reflectivity (XRR) data were acquired on a PANalytical X'Pert diffractometer equipped with a parabolic multilayer incident beam monochromator and a parallel plate diffracted beam collimator. A two layer SiwOxCyHz model was used to determine coating density from the critical angle
measurement results. This model is contemplated to offer the best approach to isolate the true SiwOxCyHz coating. The results are shown in Table 19.
[00552] VII. B. 4. From Table 17 showing the results of Example 15, the lower oxygen (28%) and higher carbon (48.4%) composition of OMCTS versus HMDSO would suggest OMCTS should have a lower density, due to both atomic mass considerations and valency (oxygen = 2; carbon = 4). Surprisingly, the XRR density results indicate the opposite would be observed, that is, the OMCTS density is higher than HMDSO density.
[00553] VII. B. 4. Without limiting the invention according to the scope or accuracy of the following theory, it is contemplated that there is a fundamental difference in reaction mechanism in the formation of the respective HMDSO-based and OMCTS-based coatings. HMDSO fragments can more easily nucleate or react to form dense nanoparticles which then deposit on the contact surface and react further on the contact surface, whereas OMCTS is much less likely to form dense gas phase nanoparticles. OMCTS reactive species are much more likely to condense on the contact surface in a form much more similar to the original OMCTS monomer, resulting in an overall less dense coating.
Example 18
Thickness Uniformity of PECVD Applied Coatings
[00554] VII. B. 4. Samples were provided of COC syringe barrels made according to the Protocol for Forming COC Syringe barrel and respectively coated with SiOx according to the Protocol for Coating COC Syringe Barrel Interior with SiOx or an OMCTS-based lubricity layer according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer. Samples were also provided of PET tubes made according to the Protocol for Forming PET Tube, respectively coated and uncoated with SiOx according to the Protocol for Coating Tube Interior with SiOx and subjected to an accelerated aging test. Transmission electron microscopy (TEM) was used to measure the thickness of the PECVD-applied coatings on the samples. The previously stated TEM procedure of Example 4 was used. The method and apparatus described by the SiOx and lubricity layer protocols used in this example demonstrated uniform coating as shown in Table 20.
Example 19
Outgassing Measurement on COC
[00555] VLB. COC tubes were made according to the Protocol for Forming COC Tube. Some of the tubes were provided with an interior barrier coating of SiOx according to the Protocol for Coating Tube Interior with SiOx, and other COC tubes were uncoated. Commercial glass blood collection Becton Dickinson 13 x 75 mm tubes having similar dimensions were also provided as above. The tubes were stored for about 15 minutes in a room containing ambient air at 45% relative humidity and 70°F (21°C), and the following testing was done at the same ambient relative humidity. The tubes were tested for outgassing following the ATC microflow measurement procedure and equipment of Example 8 (an Intelligent Gas Leak System with Leak Test Instrument Model ME2, with second generation IMFS sensor, (ΙΟμ/min full range), Absolute Pressure Sensor range: 0-10 Torr, Flow measurement uncertainty: +/- 5% of reading, at calibrated range, employing the Leak-Tek Program for automatic data acquisition (with PC) and signatures/plots of leak flow vs. time). In the present case each tube was subjected to a 22- second bulk moisture degassing step at a pressure of 1 mm Hg, was pressurized with nitrogen gas for 2 seconds (to 760 millimeters Hg), then the nitrogen gas was pumped down and the microflow measurement step was carried out for about one minute at 1 millimeter Hg pressure.
[00556] VLB. The result is shown in FIG. 57, which is similar to FIG. 31 generated in Example 8. In FIG. 57, the plots for the uncoated COC tubes are at 630, the plots for the SiOx coated COC tubes are at 632, and the plots for the glass tubes used as a control are at 634. Again, the outgassing measurement began at about 4 seconds, and a few seconds later the plots 630 for the uncoated COC tubes and the plots 632 for the SiOx barrier coated tubes clearly diverged, again demonstrating rapid differentiation between barrier coated tubes and uncoated tubes. A consistent separation of uncoated COC (>2 micrograms at 60 seconds) versus SiOx- coated COC (less than 1.6 micrograms at 60 seconds) was realized.
Example 20
Lubricity Layers
[00557] V I.B.l.a. COC syringe barrels made according to the Protocol for Forming COC Syringe Barrel were coated with a lubricity layer according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer. The results are provided in Table 21. The results show that the trend of increasing the power level, in the absence of oxygen, from 8 to 14 Watts was to improve the lubricity of the coating. Further experiments with power and flow rates can provide further enhancement of lubricity.
Example 21
Lubricity Layers - Hypothetical Example
[00558] VII. B. 4. Injection molded cyclic olefin copolymer (COC) plastic syringe barrels are made according to the Protocol for Forming COC Syringe Barrel. Some are uncoated ("control") and others are PECVD lubricity coated according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer ("lubricated syringe"). The lubricated syringes and controls are tested to measure the force to initiate movement of the plunger in the barrel (breakout force) and the force to maintain movement of the plunger in the barrel (plunger sliding force) using a Genesis Packaging Automated Syringe Force Tester, Model AST.
[00559] VII. B. 4. The test is a modified version of the ISO 7886-1: 1993 test. The following procedure is used for each test. A fresh plastic plunger with elastomeric tip taken from Becton Dickinson Product No. 306507 (obtained as saline prefilled syringes) is removed from the syringe assembly. The elastomeric tip is dried with clean dry compressed air. The elastomeric tip and plastic plunger are then inserted into the COC plastic syringe barrel to be tested with the plunger positioned even with the bottom of the syringe barrel. The filled syringes are then conditioned as necessary to achieve the state to be tested. For example, if the test object is to find out the effect of lubricant coating on the breakout force of syringes after storing the syringes for three months, the syringes are stored for three months to achieve the desired state.
[00560] VII. B. 4. The syringe is installed into a Genesis Packaging Automated Syringe Force Tester. The tester is calibrated at the start of the test per the manufacturer's specification. The tester input variables are Speed = lOOmm/minute, Range = 10,000. The start button is pushed on the tester. At completion of the test, the breakout force (to initiate movement of the plunger in the barrel) and the plunger sliding force (to maintain movement) are measured, and are found to be substantially lower for the lubricated syringes than for the control syringes.
[00561] Fig. 59 shows a vessel processing system 20 according to an exemplary embodiment of the present invention. The vessel processing system 20 comprises, inter alia, a first processing station 5501 and a second processing station 5502. Examples for such processing stations are for example depicted in Fig. 1, reference numerals 24, 26, 28, 30, 32 and 34.
[00562] The first vessel processing system 5501 contains a vessel holder 38 which holds a seated vessel 80. Although Fig. 59 depicts a blood tube 80, the vessel can also be, for example, a syringe body, a vial, a cuvette, a catheter or a pipette. The vessel can, for example, be made of glass or plastic. In case of plastic vessels, the first processing station can also comprise a mold for molding the plastic vessel.
[00563] After the first processing at the first processing station (which processing can comprise molding of the vessel, a first inspection of the vessel for defects, coating of the interior contact surface of the vessel and a second inspection of the vessel for defects, for example of the interior coating), the vessel holder 38 is transported together with the vessel 80 to a second vessel processing station 5502. This transportation is performed by a conveyor arrangement 70, 72, 74. For example, a gripper or several grippers can be provided for gripping the vessel holder 38 and/or the vessel 80 in order to move the vessel/holder combination to the next processing station 5502. Alternatively, only the vessel can be moved without the holder. However, it can be advantageous to move the holder together with the vessel in which case the holder is adapted such that it can be transported by the conveyor arrangement.
[00564] Fig. 60 shows a vessel processing system 20 according to another exemplary embodiment of the present invention. Again, two vessel processing stations 5501, 5502 are provided. Furthermore, additional vessel processing stations 5503, 5504 are provided which are arranged in series and in which the vessel can be processed, i.e. inspected and/or coated.
[00565] A vessel can be moved from a stock or holding area to the left processing station 5504. Alternatively, the vessel can be molded in the first processing station 5504. In any case, a first vessel processing step is performed in the processing station 5504, such as molding, inspection and/or coating, which can be followed by a second inspection. Then, the vessel is moved to the next processing station 5501 via the conveyor arrangement 70, 72, 74. Typically, the vessel is moved together with the vessel holder. Additional processing is performed in the second processing station 5501 after which the vessel and holder are moved to the next processing station 5502 in which more processing is performed. The vessel is then moved (again together with the holder) to the fourth processing station 5503 for a fourth processing, after which it is conveyed to storage.
[00566] Before and after each coating step or molding step or any other step which manipulates the vessel an inspection of the whole vessel, of part of the vessel and for example of an interior contact surface of the vessel can be performed. The result of each inspection can be transferred to a central processing unit 5505 via a data bus 5507. Each processing station can be connected to the data bus 5507. The processor 5505, which can be adapted in form of a central control and regulation unit, processes the inspection data, analyzes the data and determines whether the last processing step was successful.
[00567] If it is determined that the last processing step was not successful, because for example the coating comprises gaps or because the contact surface of the coating is determined to be irregular or not smooth enough, the vessel does not enter the next processing station but is either removed from the production process (see conveyor sections 7001, 7002, 7003, 7004) or conveyed back in order to be re-processed.
[00568] The processor 5505 is connected to a user interface 5506 for inputting control or regulation parameters.
[00569] Fig. 61 shows a vessel processing station 5501 according to an exemplary
embodiment of the present invention. The station comprises a PECVD apparatus 5701 for coating an interior contact surface of the vessel. Furthermore, several detectors 5702-5707 are provided for vessel inspection. Such detectors can for example be electrodes for performing electric measurements, optical detectors, like CCD cameras, gas detectors or pressure detectors.
[00570] A vessel holder 38 according to an exemplary embodiment of the present invention, together with several detectors 5702, 5703, 5704 and an electrode with gas inlet port 108, 110.
[00571] The electrode and the detector 5702 can be adapted to be moved into the interior space of the vessel 80 when the vessel is seated on the holder 38.
[00572] The optical inspection can be performed during a coating step, for example with the help of optical detectors 5703, 5704 which are arranged outside the seated vessel 80 or even with the help of an optical detector 5705 arranged inside the interior space of the vessel 80.
[00573] The detectors can comprise color filters such that different wavelengths can be detected during the coating process. The processing unit 5505 analyzes the optical data and determines whether the coating was successful or not to a predetermined level of certainty. If it is determined that the coating was most probably unsuccessful, the respective vessel is separated from the processing system or re-processed.
Example 22
Antimicrobial Treatment (Hypothetical)
[00574] The surfaces prepared as described in each preceding example are antimicrobially treated by ionic plasma deposition of silver as described in U.S. Published Patent Application 2006-0198903 Al. The treatment is found by a suitable test method to be antimicrobially effective, in that it inhibits the growth of the tested bacteria. [00575] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art and practising the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.
TABLE 1: COATED COC TUBE OTR AND WVTR MEASUREMENT
OTR WVTR
O-Si O2 (cc/ (mg/
Coating Power Flow Flow Time Tube. Tube. ID (Watts) O-Si (seem) (seem) (sec) Day) Day)
No 0.215 0. 27
Coating
A 50 HMDSO 6 90 14 0.023 0. 07
B 50 HMDSO 6 90 14 0.024 0. 10
C 50 HMDSO 6 90 7 0.026 0. 10
BLE 2: COATED PET TUBE OTR AND WVTR MEASUREMENT
OTR WVTR
O2 (cc/ (mg/
Coating Power O-Si Flow Flow Time Tube. Tube. ID (Watts) O-Si (seem) (seem) (sec) Day) Day)
Uncoated 0.0078 3.65
Control
SiOx 50 HMDSO 6 90 3 0.0035 1.95
TABLE 2 Cont'd.
Coating BIF BIF
ID (OTR) (WVTR)
Uncoated
Control
SiOx 2.2 1.9
TABLE 2A. COATED PET TUBE OTR WITH MECHANICAL SCRATCH DEFECTS
Mechanical
O-Si o2 Treat Scratch OTR
Power Flow Flow Time Length (cc/tube.d
Example O-Si (Watts) (seem) (seem) (sec) (mm) ay)* OTR E
Uncoated
Control 0.0052
Inventive HMDSO 50 6 90 3 0 0.0014 3.7
Inventive HMDSO 50 6 90 3 1 0.0039 1.3
Inventive HMDSO 50 6 90 3 2 0.0041 1.3
Inventive HMDSO 50 6 90 3 10 0.0040 1.3
Inventive HMDSO 50 6 90 3 20 0.0037 1.4
* average of two tubes
TABLE 3: COATED COC SYRINGE BARREL OTR AND WVTR MEASUREMENT
O-Si 02 OTR WVTR
Flow Flow Coating (cc/ (mg/
Syringe O-Si Power Rate Rate Time Barrel. Barrel. BIF BIF
Example Coating Composition (Watts) (seem) (seem) (sec) Day) Day) (OTR) (WVTR)
A Uncoated 0.032 0.12
Control
B SiOx HMDSO 44 6 90 7 0.025 0.11 1.3 1.1
Inventive
Example
C SiOx HMDSO 44 6 105 7 0.021 0.11 1.5 1.1
Inventive
Example
D SiOx HMDSO 50 6 90 7 0.026 0.10 1.2 1.2
Inventive
Example
E SiOx HMDSO 50 6 90 14 0.024 0.07 1.3 1.7
Inventive
Example
F SiOx HMDSO 52 6 97.5 7 0.022 0.12 1.5 1.0 Inventive
Example
G SiOx HMDSO 61 6 105 7 0.022 0.11 1.4 1.1
Inventive
Example
H SiOx HMDSO 61 6 120 7 0.024 0.10 1.3 1.2
Inventive
Example
I SiOx HMDZ 44 6 90 7 0.022 0.10 1.5 1.3
Inventive
Example
SiOx HMDZ 61 6 90 7 0.022 0.10 1.5 1.2
Inventive
Example
SiOx HMDZ 61 6 105 7 0.019 0.10 1.7 1.2
Inventive
Example TABLE 4: SIOx COATING THICKNESS (NANOMETERS) DETECTED BY TEM
Oxygen
HMDSO Flow
Thickness Power Flow Rate Rate
Sample (nm) (Watts) (seem) (seem)
Inventive Example
HMDSO 25-50 39 60 A
Inventive Example
HMDSO 20-35 39 90 B
TABLE 5: ATOMIC RATIOS OF THE ELEMENTS DETECTED (in parentheses, Concentrations in percent, normalized to 100% of elements detected)
Plasma
Sample Coating Si O C
PET Tube - Comparative Example - 0.08 (4.6%) 1 (31.5%) 2.7 (63.9%)
Polyethylene Terephthalate - _ 1 (28.6%) 2.5 (71.4%) Calculated
Coated PET Tube - Inventive χ 2.4 (51.7%) 0.57 (9.2%) Example
TABLE 6: EXTENT OF HOLLOW CATHODE PLASMA IGNITION
Sample Power Time Hollow Cathode Plasma Ignition Staining Result
A 25 Watts 7 sec No Ignition in gas inlet 310, good
Ignition in restricted area 292
B 25 Watts 7 sec Ignition in gas inlet 310 and poor
restricted area 292
C 8 Watts 9 sec No Ignition in gas inlet 310, better
Ignition in restricted area 292
D 30 Watts 5 sec No Ignition in gas inlet 310 or best
restricted area 292 TABLE 7: FLOW RATE USING GLASS TUBES
Run #1 ^g Run #2 ^g Average ^g
Glass Tube / min.) / min.) / min.)
1 1.391 1.453 1.422
2 1.437 1.243 1.34
3 1.468 1.151 1.3095
4 1.473 1.019 1.246
5 1.408 0.994 1.201
6 1.328 0.981 1.1545
7 Broken Broken Broken
8 1.347 0.909 1.128
9 1.171 0.91 1.0405
10 1.321 0.946 1.1335
11 1.15 0.947 1.0485
12 1.36 1.012 1.186
13 1.379 0.932 1.1555
14 1.311 0.893 1.102
15 1.264 0.928 1.096
Average 1.343 1.023 1.183
Max 1.473 1.453 1.422
Min 1.15 0.893 1.0405
Max-Min 0.323 0.56 0.3815
Std Dev 0.097781 0.157895 0.1115087
TABLE 8: FLOW RATE USING PET TUBES
Uncoated Run #1 ^g / Run #2 ^g / Average
PET min.) min.) / min.)
1 10.36 10.72 10.54
2 11.28 11.1 11.19
3 11.43 11 .22 11.325
4 11.41 11 .13 11.27
5 11.45 11 .17 11.31
6 11.37 11 .26 11.315
7 11.36 11 .33 11.345
8 11.23 11 .24 11.235
9 11.14 11 .23 11.185
10 11.1 11 .14 11.12
11 11.16 11 .25 11.205
12 11.21 11 .31 11.26
13 11.28 11 .22 11.25
14 10.99 11 .19 11.09
15 11.3 11 .24 11.27
Average 11.205 11.183 11.194
Max 11.45 11.33 11.345
Min 10.36 10.72 10.54
Max-Min 1.09 0.61 0.805
Std Dev 0.267578 0.142862 0.195121
TABLE 9: FLOW RATE FOR SiOx COATED PET TUBES
Coated Run #1 ^g Run #2 ^g Average
PET / min.) / min.) ^g / min.)
1 6.834 6.655 6.7445
2 9.682 9.513 Outliers
3 7.155 7.282 7.2185
4 8.846 8.777 Outliers
5 6.985 6.983 6.984
6 7.106 7.296 7.201
7 6.543 6.665 6.604
8 7.715 7.772 7.7435
9 6.848 6.863 6.8555
10 7.205 7.322 7.2635
11 7.61 7.608 7.609
12 7.67 7.527 7.5985
13 7.715 7.673 7.694
14 7.144 7.069 7.1065
15 7.33 7.24 7.285
Average 7.220 7.227 7.224
Max 7.715 7.772 7.7435
Min 6.543 6.655 6.604
Max-Min 1.172 1.117 1.1395
Std Dev 0.374267 0.366072 0.365902
TABLE 10: WETTING TENSION MEASUREMENT OF COATED AND UNCOATED TUBES
Wetting Tension
Example Tube Coating (dyne/cm)
Reference uncoated glass 72
Inventive Example PET tube coated with 60
SiOx according to SiOx
Protocol
Comparative Example uncoated PET 40
Inventive Example PET tube coated 34
according to Hydrophobic
layer Protocol
Comparative Example Glass (+silicone fluid) 30
glass syringe, Part No.
TABLE 11: WATER MASS DRAW (GRAMS)
Pressurization Time (days) Tube 0 27 46 81 108 125 152 231
BD PET (commercial control) 3.0 1.9 1.0
Uncoated PET (internal control) 4.0 3.1 2.7
SiOx-Coated PET (inventive example) 4.0 3.6 3.3
TABLE 12: CALCULATED NORMALIZED AVERAGE VACUUM DECAY
RATE AND TIME TO 10% VACUUM LOSS
Normalized Average
Decay rate (delta Time to 10% Loss
Tube mL/initial mL.da) (months) - Accelerated
BD PET 0.0038 0.9
(commercial control)
Uncoated PET 0.0038 0.9
(internal control)
SiOx-Coated PET 0.0018 1.9
(inventive example)
TABLE 13: SYRINGE BARRELS WITH LUBRICITY LAYER, ENGLISH UNITS
O-Si 02 Avg.
Power, Flow, Flow, time Force,
Sample (Watts) (seem) (seem) (sec) (lb.) St.dev.
Glass with Silicone No No No No 0.58 0.03 coating coating coating coating
Uncoated COC No No No No 3.04 0.71 coating coating coating coating
A 11 0 1.09 0.27 B 17 14 2.86 0.59 C 33 14 3.87 0.34 D 90 30 2.27 0.49
Uncoated COC 3.9 0.6 SiOx on COC 4.0 1.2 E 11 1.25 0 5 2.0 0.5 F 11 2.5 0 5 2.1 0.7 G 11 5 0 5 2.6 0.6 H 11 2.5 0 10 1.4 0.1 I 22 5 0 5 3.1 0.7 J 22 2.5 0 10 3.3 1.4 K 22 5 0 5 3.1 0.4 TABLE 13: SYRINGE BARRELS WITH LUBRICITY LAYER, METRIC UNITS
O-Si o2 Avg.
Power, Flow, Flow, time Force,
Sample (Watts) (seem) (seem) (sec) (Kg.) St.dev,
Glass syringe with No No No No 0.26 0.01 sprayed silicone coating coating coating coating
Uncoated COC No No No No 1.38 0.32 coating coating coating coating
A 11 6 0 7 0.49 0.12
B 17 6 0 14 1.29 0.27
C 33 6 0 14 1.75 0.15
D 6 6 90 30 1.03 0.22
Uncoated COC - - - 1.77 0.27 SiOx on COC , per
protocol 1.81 0.54
E 11 1.25 - 5 0.91 0.23
F 11 2.5 - 5 0.95 0.32
G 11 5 - 5 1.18 0.27
H 11 2.5 - 10 0.63 0.05
I 22 5 - 5 1.40 0.32
J 22 2.5 - 10 1.49 0.63
K 22 5 5 1.40 0.18
TABLE 14: PLUNGER SLIDING FORCE MEASUREMENTS OF HMDSO- AND
OMCTS-BASED PLASMA COATINGS
Coating
Si-0 Coating Maximum Normalized
Coating Flow Rate Power Force Maximum
Example Description Monomer Time ( sec) (seem) (Watts) (lb, kg.) Force
A uncoated 3.3, 1.5 1.0
Control
B HMDSO HMDSO 7 6 8 4.1, 1.9 1.2
Coating
C OMCTS OMCTS 7 6 8 1.1, 0.5 0.3
Lubricity layer
D uncoated 3.9, 1.8 1.0 Control
E OMCTS OMCTS 7 6 11 2.0, 0.9 0.5 Lubricity layer
F Two Layer 1 COC 14 6 50
Coating Syringe
Barrel +
SiOx
2 OMCTS 7 6 8 2.5, 1.1 0.6 Lubricity
layer
G OMCTS OMCTS 5 1.25 11 2, 0.9 0.5 Lubricity layer
H OMCTS OMCTS 10 1.25 11 1.4, 0.6 0.4 Lubricity layer
TABLE 15: OTR AND WVTR MEASUREMENTS (Prophetic)
OTR WVTR
Sample (cc/barrel.day) (gram/barrel.day)
COC syringe- Comparative Example 4.3 X 3.0 Y
PVdC-COC laminate COC syringe- Inventive X Y
Example
TABLE 16: OPTICAL ABSORPTION OF SiOx COATED PET TUBES (NORMALIZED TO UNCOATED PET TUBE)
Average
Coating Absorption (@ 615
Sample Time nm) Replicates Stdev.
Reference (uncoated) - 0.002-0.014 4
Inventive A 3 sec 0.021 8 0.001
Inventive B 2 x 3 sec 0.027 10 0.002
Inventive C 3 x 3 sec 0.033 4 0.003
TABLE 17: ATOMIC CONCENTRATIONS (IN PERCENT, NORMALIZED TO 100% OF ELEMENTS DETECTED) AND TEM THICKNESS
Figure imgf000144_0001
TABLE 18: VOLATILE COMPONENTS FROM SYRINGE OUTGASSING
Me3SiOH Higher SiOMe
Coating Monomer (ng/test) oligomers (ng/test)
Uncoated COC syringe - Comparative Example Uncoated ND ND
HMDSO-based Coated
COC syringe- Comparative
Example HMDSO 58 ND
OMCTS- based Coated
COC syringe- Inventive
Example OMCTS ND 26
TABLE 19: PLASMA COATING DENSITY FROM XRR DETERMINATION
Sample Layer Density g/cm3
HMDSO-based Coated Sapphire - Comparative Example SiwOxCyHz 1.21
OMCTS- based Coated Sapphire - Inventive Example SiwOxCyHz 1.46
TABLE 20: THICKNESS OF PECVD COATINGS BY TEM
TEM TEM TEM
Sample ID Thickness I Thickness II Thickness III
Protocol for Forming COC 164 nm 154 nm 167 nm
Syringe Barrel; Protocol
for Coating COC Syringe
Barrel Interior with SiOx
Protocol for Forming COC 55 nm 48nm 52 nm
Syringe Barrel; Protocol
for Coating COC Syringe
Barrel Interior with
OMCTS Lubricity layer
Protocol for 28 nm 26 nm 30 nm
Forming PET Tube;
Protocol for Coating Tube
Interior with SiOx
Protocol for
Forming PET Tube
(uncoated)
TABLE 21: OMCTS LUBRICITY LAYER PERFORMANCE (English Units)
Percent
Average Force
Plunger Reduction OMCTS
Force (vs Power Flow
Sample (lbs.)* uncoated) (Watts) (seem)
Comparative
(no coating) 3.99 —
Sample A 1.46 63% 14 0.75
Sample B 1.79 55% 11 1.25
Sample C 2.09 48% 8 1.75
Sample D 2.13 47% 14 1.75
Sample E 2.13 47% 11 1.25
Sample F 2.99 25% 8 0.75
Average of 4 replicates
TABLE 21: OMCTS LUBRICITY LAYER PERFORMANCE (Metric Units)
Percent
Average Force
Plunger Reduction OMCTS
Force (vs Power Flow
Sample (lbs.)* uncoated) (Watts) (seem)
Comparative
(no coating) 1.81
Sample A 0.66 63% 14 0.75
Sample B 0.81 55% 11 1.25
Sample C 0.95 48% 8 1.75
Sample D 0.96 47% 14 1.75
Sample E 0.96 47% 11 1.25
Sample F 1.35 25% 8 0.75
Above force measurements are the average of 4 samples.

Claims

1. A method of making an antimicrobial medical device comprising:
• providing a medical device or material or portion thereof comprising a contact surface;
• applying a first treatment to the contact surface of SiOx, SiOxCy, or SiNxCy; and
• before or after the first treatment, applying a second antimicrobially effective treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, to the contact surface.
2. The method of claim 1, in which the metal comprises silver.
3. The method of claim 1, in which the second treatment is applied by at least one of the following processes:
• a controlled cathodic arc process;
• ionic plasma deposition (IPD);
• application of a fluid coating containing ions of the metal; or
• adding silver mixed with a ceramic, such as zirconium phosphate, directly into the material of the contact surface.
4. The method of claim 1, in which the second treatment is ionic plasma deposition.
5. The method of claim 1, in which the second treatment is a controlled cathodic arc process.
6. The method of claim 1, in which the first coating comprises a barrier coating of
SiOx, in which x is from about 1.5 to about 2.9, applied by:
• providing a contact surface;
• providing a reaction mixture comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas;
• forming plasma in the reaction mixture that is substantially free of hollow cathode plasma;
• contacting the contact surface with the reaction mixture; and
• depositing the coating of SiOx on at least a portion of the contact surface.
7. The method of claim 6, further comprising, before or after forming plasma in the reaction mixture that is substantially free of hollow cathode plasma, also forming a plasma in the reaction mixture that contains hollow cathode plasma.
8. The method of claim 1, in which the first coating comprises a barrier coating of
SiOx, in which x is from about 1.5 to about 2.9, applied by:
• providing a vessel wall;
• providing a reaction mixture comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas;
• forming plasma in the reaction mixture by energizing the vicinity of the precursor with electrodes supplied with electric power at equal to or more than 5 W/ml. of plasma volume;
• contacting the vessel wall with the reaction mixture; and
• depositing the coating of SiOx on at least a portion of the vessel wall.
9. The method of claim 8, in which the plasma is made by energizing the vicinity of the precursor with electrodes supplied with electric power at from 6 W/ml. to 150 W/ml. of plasma volume, optionally from 7 W/ml. to 100 W/ml of plasma volume, optionally from 7 W/ml. to 20 W/ml of plasma volume.
10. The method of claim 1, in which the first coating is a hydrophobic first layer having one of the following atomic ratios, measured by X-ray photoelectron spectroscopy (XPS), SiwOxCy or SiwNxCy, where w is 1, x in this formula is from about 0.5 to 2.4, and y is from about 0.6 to about 3 of the type made by:
• providing a precursor selected from a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, or a combination of any two or more of these precursors;
• applying the precursor to a contact surface under conditions effective to form a coating; and
• polymerizing or crosslinking the coating, or both, to form a hydrophobic surface having a different contact angle, alternatively a higher contact angle, alternatively a lower contact angle, than the untreated contact surface.
11. The method of claim 10, in which the precursor comprises hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, hexamethylcyclotrisiloxane,
octamethylcyclotetrasiloxane, decamethylcyclo-pentasiloxane dodecamethylcyclohexasiloxane, a silatrane, a silquasilatrane, a silproatrane, an azasilatrane, an azasilquasiatrane, an
azasilproatrane, SST-eMOl poly(methylsilsesquioxane), in which each R is methyl, SST- 3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which 90% of the R groups are methyl and 10% are hydrogen atoms, methyl trimethoxysilane, or a combination of any two or more of these.
12. The method of claim 10 or 11, in which the precursor comprises
octamethylcyclotetrasiloxane.
13. The method of any of claims 10-12, in which the applying step is carried out by vaporizing the precursor and providing it in the vicinity of the contact surface.
14. The method of any of claims 10-13, in which a plasma is formed in the vicinity of the contact surface.
15. The method of any of claims 10-14, in which the precursor or its reaction product is applied to the contact surface at a thickness of 10 to 5000 nm thick, optionally 10 to 1000 nm thick, optionally 10 to 200 nm thick, optionally 20 to 100 nm thick.
16. The method of any of claims 10-15, in which the contact surface comprises glass.
17. The method of any of claims 10-15, in which the contact surface comprises a polymer.
18. The method of claim 17, in which the polymer is selected from the group consisting of: a polycarbonate polymer, an olefin polymer, a cyclic olefin copolymer, a polypropylene polymer, a polyester polymer and a polyethylene terephthalate polymer.
19. The method of any of claims 10-18, in which the precursor is contacted with a plasma made by energizing the vicinity of the precursor with electrodes powered at a frequency of 10 kHz to 2.45 GHz.
20. The method of any of claims 10-19, in which the precursor is contacted with a plasma made by energizing the vicinity of the precursor with electrodes supplied with electrical power having a frequency from about 13 to about 14 MHz.
21. The method of any of claims 10-20, in which the precursor is contacted with a plasma made by energizing the vicinity of the precursor with electrodes supplied with electric power at less than 10 Watts per ml. of plasma volume.
22. The method of any of claims 10-20, in which the precursor is contacted with a plasma made by energizing the vicinity of the precursor with electrodes supplied with electric power from 0.1 to 4 Watts per ml. of plasma volume.
23. The method of any of claims 10-20, in which the precursor is contacted with a plasma made by energizing the vicinity of the precursor with electrodes supplied with electric power from 0.2 to 2 Watts per ml. of plasma volume.
24. The method of any of claims 10-23, further comprising a barrier coating on the contact surface.
25. The method of claim 24, in which the barrier coating is an oxygen barrier coating.
26. The method of claim 24 or 25, in which the barrier coating is a water barrier coating.
27. The method of any of claims 10-26, configured as a sample tube, a syringe, a vial, a catheter, or a cuvette.
28. A medical device made by the method of any of claims 1-27.
29. A cell preparation tube comprising:
• a wall made of thermoplastic material having an internal surface defining a
lumen;
• a hydrophobic layer on the internal surface made by providing a precursor
selected from a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, or a combination of any two or more of these precursors; and using PECVD to form a coating on the internal surface having one of the following atomic ratios, measured by X-ray photoelectron spectroscopy (XPS), SiwOxCy or SiwNxCy, where w is 1, x in this formula is from about 0.5 to 2.4, and y is from about 0.6 to about 3;
• a second antimicrobially effective coating or treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc applied to the hydrophobic layer; and
• an aqueous sodium citrate reagent disposed in the lumen of the tube in an amount effective to inhibit coagulation of blood introduced into the tube.
30. The invention of claim 29, in which the hydrophobic layer precursor comprises hexamethyldisiloxane or tetramethyldisiloxane.
31. The invention of any preceding claim, in which the contact surface is a material contacting surface of one or more selected from the group consisting of: an ACL/PCL
Reconstruction System, an adapter, an adhesion barrier, an agar petri dish, an anesthesia unit, an anesthesia ventilator, an angiographic catheter, an ankle replacement, an aortic valve
replacement, an apnea monitor, an applicator, an argon enhanced coagulation unit, an artificial facet replacement, an artificial heart, an artificial heart valve, an artificial organ, an artificial pacemaker, an artificial pancreas, an artificial urinary bladder, an aspirator, an atherectomy catheter, an auditory brainstem implant, an auto transfusion unit, a bag, a balloon catheter, a bare-metal stent, a beaker a bileaflet valve, a biliary stent, a bio implant, a bioceramic device, a bioresorbable stent, a biphasic cuirass ventilation, a blood culture device, a blood sample cassette, a blood sampling system, a bottle, a brain implant, a breast implant, a breast pump, a buccal sample cassette, a buttock augmentation, a caged-ball valve, a cannulated screw, a capillary blood collection device, a capsular contracture, a cardiac catheter, a cardiac defibrillator (external or internal), a cardiac output injectate kit and cable, a cardiac prosthesis, a cardiac shunt, a catheter, a cell lifter, a cell scraper, a cell spreader, a central cenous catheter, a centrifuge component, a cerebral shunt, a CHD stent, a chemical transfer pump, a chin augmentation, a chin sling, a cochlear implant, a collection and transport device, a colonic Stent, a compression pump, a connector, a container, a contraceptive implant, a cornea implant, a coronary stent, a Cotrel-Dubousset instrumentation, a cover glass, a cranio maxillofacial implant, a cryo/freezer box, a dehydrated culture media device, a deltec cozmo, a dental implant, a depression microscopic slide, a dewar flask, a DHS/DCS & angled blade plate, a diabetes accessory, a diaphragm pump, a diaphragmatic pacemaker, a direct testing and serology device, a disposable domes and kits, a double channel catheter, a double-lumen catheter, a drug-eluting stent, a duodenal stent, a dynamic compression plate, a dynamic hip screw, an elastomeric pump, an elbow replacement, an elbowed Catheter, an electrocardiograph (ECG), an electrode Catheter, an electroencephalograph (EEG), an electronic thermometer, an electrosurgical unit, an endoscope, an enteral feeding pump, an environmental systems device, an esophageal stent, an external fixator, an external pacemaker, a female catheter, a fetal monitor, a film, a flat microscopic slide, a flow-restricted, oxygen-powered ventilation device, a fluid administration product, a fluid-filled catheter, a foley catheter, a forceps, a glaucoma valve, goggles, a Gouley catheter, a graft, a grommet, a Greuntzig balloon catheter, a Harrington rod, a heart valve, a heart-lung machine, a HeartMate left ventricular assist device, a hip prosthesis, a hip
replacement, a hip resurfacing, a holder, a human-implantable RFID chip, a hypoxicator, a susceptibility device, an Implanon, an implant (medicine), an implantable cardioverter- defibrillator, an implantable defibrillator, an implantable device, an implantable gastric stimulation, an incubator, an in-dwelling catheter, an infusion set, an inhaler, an insulin pen, an insulin pump, an interlocking nail, an internal fixation, an intra-aortic balloon pump, an intramedullary rod, an intrathecal pump, an intravenous Catheter, an invasive blood pressure unit, an iron lung, an IV adapter, an IV catheter, an IV connector, an IV fluch syringe, an IV product, an IV site maintenance device, an IV stopcock, a joint replacement of the hand, a joint replacement, a keratometer, a Kirschner wire, a knee cartilage replacement therapy, a knee replacement, a lancet, a laparoscopic insufflator, large fragment implant, a lensometer, a liquid ventilator, a lytic bacteriophage, a medical grafting, a medical Pump, a medical ventilator, microbiology equipment and supplies, a microbiology testing device, a microchip implant (human), a microscopic Slide, a microtiter plate, a midline catheter, a mini dental implant, a mini Fragment Implant, a Minimplant, a molecular diagnostics device, a mycobacteria testing device, a nail, a wire, a pin, a needleless IV connector, a Nelaton urinary catheter, a Norplant
implantable birth control device, an O'Neil aspirating and irrigating needle, an O'Neil balloon infuser, an O'Neil intermittent urinary catheter, a contact lens, an orthopedic implant, an osseointegration implant, an oxinium replacement joint material, a pacemaker, a pacing Catheter, a pain management pump, a palatal obturator, a pancreatic Stent, a penile prosthesis, a penis enlargement device, a peripheral stent, a Peripherally Inserted Central Catheter (PICC), a peristaltic pump, a peritoneovenous shunt, a petri dish, a phonocardiograph, a phototherapy unit, a Pipette, a polyaxial screw, a port (medical), a portacaval shunt, a positive airway pressure device, a prepared media device, a pressure accessory or cable, a pressure transducer, a prostatic catheter, a prostatic stent, a pulmonary artery catheter, a pule oximeter, a radiant warmer, a radiation-therapy machine, a razor blade, a re-constructive prosthesis, a right-to-left shunt, a nerve stimulator, a safety supply, a sample collection container, a sample collection tube, a Sample Collection/Storage Device, a self-expandable metallic stent, a self-retaining catheter, a shaker flask, a shoulder replacement, a shunt (medical), a skin implant, a small fragment Implant, a snare catheter, Sphygmomanometer, a spinal cord stimulator, a spine surgery, a Stain, a Reagent, a static control supply, a stent graft, a stent, a sterility supply, a sterilizer, a stirrer, a subdermal implant, a surgical drill and saw, a surgical microscope, a suture, a swab, a Swan- Ganz catheter, a syringe driver, a temperature monitor, a Tenckhoff catheter, a Tiemann catheter, a tilting-disk valve, a tissue grinder, a toposcopic catheter, a transdermal implant, tubing, a tubing connector, a tubing link, a two-way catheter, ultrasonic nebulizer, an ultrasound sensor, an unicompartmental knee arthoplasty, an ureteral catheter, an ureteral stent, an urethral catheter, a urinary catheter, a urine sample cassette, a vascular ring connector, a vascular stent, a ventilator, ventricular assist device, vertebral fixation, a winged Catheter and X-ray diagnostic equipment.
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