EP1652787A1 - Piercable flexible device for closing a container for liquid - Google Patents
Piercable flexible device for closing a container for liquid Download PDFInfo
- Publication number
- EP1652787A1 EP1652787A1 EP05022082A EP05022082A EP1652787A1 EP 1652787 A1 EP1652787 A1 EP 1652787A1 EP 05022082 A EP05022082 A EP 05022082A EP 05022082 A EP05022082 A EP 05022082A EP 1652787 A1 EP1652787 A1 EP 1652787A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- opening
- membrane
- incisions
- elastic membrane
- liquid
- Prior art date
- Legal status (The legal status 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 status listed.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/1406—Septums, pierceable membranes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5082—Test tubes per se
- B01L3/50825—Closing or opening means, corks, bungs
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D51/00—Closures not otherwise provided for
- B65D51/002—Closures to be pierced by an extracting-device for the contents and fixed on the container by separate retaining means
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/142—Preventing evaporation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
- B01L2300/042—Caps; Plugs
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/046—Function or devices integrated in the closure
- B01L2300/049—Valves integrated in closure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0633—Valves, specific forms thereof with moving parts
- B01L2400/0638—Valves, specific forms thereof with moving parts membrane valves, flap valves
Definitions
- the invention relates to a flexible device for covering liquid containers, which can be pierced by the action of a rod-shaped object and which returns to its original shape after removal of the rod-shaped object.
- a criterion to be considered when establishing tests on fully automatic diagnostic devices is the shelf life of the reagents when stored in the device, the so-called on-board stability, which is significantly influenced by the conditions in the device. Particularly problematic is the evaporation-related mass loss of liquid reagents.
- the use of reagents of a defined composition is essential, so that changes in concentration caused by fluid losses can impair the quality or the so-called performance of the entire test.
- the reason for the evaporation of liquid reagents is that they have to be directly accessible to the automatic pipettors and therefore are not hermetically sealed as a rule.
- a particularly impervious protection against evaporation are sealing caps that hermetically seal the opening of the reagent container, such as swivel or snap closures.
- this type of evaporation protection is only suitable for those devices that also have a corresponding device that automatically performs the opening and reclosing.
- sealing plugs which are preferably made of highly elastic materials, such. As rubber are made, widely used. Examples of such devices can be found in EP 0 509 281 B1, EP 0 097 591 B1 and FR 27 72 727 A1.
- the advantage of these flexible plugs is that they have inlet openings for cannulas and other rod-shaped objects, which have a certain flexibility due to the elasticity of the material used. As a result, on the one hand, the inlet openings can adapt to the diameter of the inserted object and, on the other hand, reseal after removal of the object. Difficulties arise, however, if z.
- the object of the present invention was therefore to provide a device for closing fluid containers, which firstly contributes to the reduction of evaporation effects and thus to a higher on-board stability of liquid reagents, secondly almost universally for a very wide variety of liquid containers and pipetting devices can be used in diagnostic devices without modifications to the design of the liquid containers themselves or even the devices would be required and thirdly represents a cost-effective alternative to the previously known closure devices.
- the present device for covering liquid containers is preferably used for the cover of reagent containers used in equipment, which process steps, such as. B. perform the pipetting or mixing of liquids automatically.
- the device consists of a membrane, that is to say a separating layer or separating layer, which is suitable for separating two partial regions or compartments.
- the membrane is provided with at least two radially arranged cuts and is preferably mounted on an opening of a liquid container, so that its opening is completely covered.
- the term "cut” is to be understood as a cut which completes the membrane, i. H. severed in their entire thickness.
- the attachment of the membrane may be by means of chemical or mechanical adhesion promoters which provide a sealing, fixing connection between the membrane and the edge of the liquid container defining the opening.
- the chemical adhesion is the Adhesion, which is produced by means of adhesives, preferably with the aid of liquid adhesives, between two parts to be joined, while mechanical adhesion is to be understood as adhesion, which is influenced by the nature of surfaces, such. As the micro-clamping porous or fibrous surfaces such.
- Velcro closures are examples of the Adhesion, which is produced by means of adhesives, preferably with the aid of liquid adhesives, between two parts to be joined.
- a preferred variant is the use of a self-adhesive membrane which is treated on one side, at least in the area which is to be brought into direct contact with the liquid container, with an adhesive, as z.
- B. of commercially available self-adhesive films or adhesive labels is known.
- This embodiment has the advantage that the self-adhesive membranes on a carrier layer, such. B. a protective film can be applied, from which they can be easily detached without losing their adhesive power. To allow easier handling of the membranes and z.
- the inventive device may also be provided with one or more Abziehlaschen.
- Another type of attachment of the membrane is the use of a cap which fixes the membrane mechanically on the edge defining the opening of a liquid container.
- Coupling caps in the sense of the present invention have a preferably circular opening whose opening cross-section allows the passage of the rod-shaped object to be used.
- Particularly advantageous is the use of such drilled screw caps, if the liquid container to be closed has a screw thread.
- the device according to the invention may be advantageous not to fasten the device according to the invention on the edge of the liquid container itself, but on the edge of the cap. It is possible to mount the device both on the outer edge and on the edge facing the inside of the cap.
- the inventive device for covering liquid containers consists of a flexible membrane, which is provided with at least two incisions, which meet in a common initial or apex, so are arranged radially.
- the two incisions are arranged so that an angle of 10 ° to 180 °, preferably from 20 ° to 120 °, particularly preferably from 45 ° to 90 ° is formed.
- the number of incisions and the angular intervals between the incisions can be varied so as to result in an optimum ratio between the passage width, minimum frictional resistance and the greatest possible evaporation protection.
- a further preferred embodiment of the device according to the invention consists of a membrane which is provided with 3 to 12, preferably with 4 to 10, particularly preferably with 6 advantageously equally long incisions.
- An incision can be made by means of a straight, wavy or serrated cut.
- the incisions are arranged equiangularly to each other, so that a plurality of isosceles triangles arise whose bases are connected to the peripheral edge of the membrane.
- the length of the incisions originating from the vertex can be varied and is preferably chosen so that the region of the rod-shaped object which has the largest diameter and which is still intended to penetrate the covering device is provided with passage.
- the device according to the invention can be pierced by the action of a rod-shaped object and returns to its original shape after removal of the rod-shaped object.
- a rod-shaped object Become by the action of, for example, a pipettor the free ends of the triangles, which are cut into the membrane, displaced into the interior of the liquid container, whereby an opening is ensteht, which adapts flexibly, ie with low friction to the diameter of the pipettor.
- the membrane triangles After removal of the pipettor, the membrane triangles return to their original position due to the elasticity of the material used and thus close the opening of the liquid container. This process is repeatable many times.
- Rod-shaped objects for the purposes of the present invention are, for example, devices for transferring liquids, such as pipettors or cannulas, or devices for mixing liquids, such as stirring rods, and are generally cylindrical or conical-shaped. The end of such rod-shaped objects may be pointed, rounded or blunt.
- the flexible membrane preferably consists of an elastic, vapor-impermeable material.
- the membrane material consists of a material from the group polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polystyrene (PS), polyamide (PA), polybutylene terephthalate (PBT), polycarbonate, (PC), polyimides (PI) , Natural rubber, silicone, bromobutyl and chlorobutyl rubber.
- PE polyethylene
- PP polypropylene
- PET polyethylene terephthalate
- PS polystyrene
- PA polyamide
- PBT polybutylene terephthalate
- PC polycarbonate
- PI polyimides
- Natural rubber silicone, bromobutyl and chlorobutyl rubber.
- the thickness of the flexible membrane is preferably not greater than 150 ⁇ m and is advantageously between 40 ⁇ m and 100 ⁇ m, more preferably between 50 ⁇ m and 80 ⁇ m.
- the device according to the invention is characterized in that arranged at the apex of the radiating th incisions is a circular, oval or polygonal opening, the z. B. can be created by punching.
- the diameter of this opening corresponds to the diameter of that part of the rod-shaped object which passes first when entering the liquid container and at the exit last the closure device, so that z. B. liquid residues that adhere to the outside of a pipettor are stripped on the membrane. In this way, excessive contamination of the closure device can be avoided, whereby the risk of mixing of z. As different reagents is reduced.
- FIG. 1 shows various embodiments of the device according to the invention for covering liquid containers in a plan view.
- the device consists of an elastic membrane (1), which is provided with at least two incisions (2), which are arranged radially.
- Fig. 1 a and Fig. 1 b show devices according to the invention, which are each provided with six incisions (2).
- the equiangular arrangement of the incisions each produce six isosceles triangles (3) whose bases are connected to the peripheral edge of the membrane.
- the device in Fig. 1 b has at the apex of the radially arranged incisions via a circular opening (4).
- Fig. 1 a and b are provided with three pull tabs (5), which are designed by appropriate cutting of the membrane and facilitate the handling of the devices.
- Fig. 1 c shows a device according to the invention provided with two cuts arranged to form an angle (6) of about 70 °.
- Fig. 1d shows a device according to the invention, which is provided with six incisions, wherein the incisions are not all the same length.
- the shape or the outline of the devices depends on the shape of the opening of the liquid container to be covered. While the devices of Figures 1 a to c are particularly suitable for covering circular openings, a device having a shape as shown in Figure 1 d can be used to cover oval openings.
- Fig. 1d further illustrates that the area of the membrane rendered pierceable by the sipes need not be in the center of the device, but can also be placed at a position other than the central position.
- FIG. 2 illustrates the attachment of a device according to the invention for covering liquid containers (7), which in this example are provided with a screw thread (8) and for which a drilled screw cap (9) with a central, circular opening is available.
- Fig. 2a shows that the device according to the invention can be applied directly to the edge of the opening of the liquid container (10). The fixation of the membrane can be achieved by adhesion promoters such. As an adhesive on the support surface, caused by the mechanical attachment by screwing the screw cap or by a combination of both.
- 2b shows that the device according to the invention for covering can also be applied to the outside of the edge defining the opening of the screw cap, the membrane in this case preferably being fastened with the aid of a bonding agent.
- FIG. 3 illustrates the expediency of a device (1) according to the invention, which in this case consists of an elastic membrane provided with six cuts and applied to the opening of a cap (11), which in turn rests on the opening of a liquid container (12) , The level of the liquid inside the container is indicated by a dashed line.
- FIG. 3a shows how a pipettor (13), which has regions of different diameter along its longitudinal axis, pierces the device according to the invention with the tip, ie with the region of the smallest diameter (14).
- 3b and 3c show how, as a result of the increasing outer diameter (15, 16) of the pipettor, the free ends of the membrane triangles (3) are displaced into the interior of the container, whereby the opening flexibly adapts to the respective outer diameter of the pipettor.
- Example 1 Reduction of evaporation-related weight losses
- D-dimer cross-linked fibrin derivatives containing the D-dimer domain
- All three reagents are aqueous solutions that are mixed with a plasma sample to perform the assay.
- reagent B is a suspension of latex particles coated with a D-dimer specific monoclonal antibody (see, for example, EP 0 122 478-B2)
- reagents A and C are known in the art essentially to buffered saline solutions.
- the Sysmex® CA-560 Analyzer (CA-560 for short) has a temperature-controllable position (15 ⁇ 1 ° C) for a test reagent container and other reagent container positions that can not be adjusted for temperature and therefore at room temperature (approx 25 ° C).
- Test reagent A was placed in the tempered position while test reagents B and C were placed in non-tempered positions.
- the reagent containers were 5 ml glass threaded bottles with an opening diameter of about 11 mm.
- reagent containers A, B and C were opened and placed in the designated positions of the CA-560, either with or without the use of a capping device according to the present invention.
- a self-adhesive polypropylene membrane was used, which was coated on one side with cellulose and treated on the other side with an adhesive was, so that a total film thickness of 62 microns and a weight of 93 g / qm resulted.
- the membranes were circular cut, had a diameter of about 12 mm and were provided with 8 radial, equiangularly arranged and equally long incisions.
- the membranes were glued to the upper edges of the reagent containers and additionally stabilized with a drilled screw cap, as also shown in Fig. 2a.
- Each of the reagent containers contained 2 ml of reagent liquid at time t (0).
- a mass determination of the filled reagent containers was carried out at time t (0) and after 18 hours, at time t (18).
- the relative mass loss of the reagent liquids was determined from the difference ( ⁇ ) of the mass at time t (0) and the mass at time t (18).
- the reagent containers each containing 2 ml of reagent liquid, were first opened, placed in the CA-560, and at time t (0), a test for quantitative determination of D-dimer in a lower D plasma sample -Dimer concentration (control LOW) and performed in a plasma sample of high D-dimer concentration (control HIGH).
- control LOW D plasma sample -Dimer concentration
- control HIGH plasma sample of high D-dimer concentration
- the reagents were stored in the equipment under the conditions described in 1), 2) or 3), and after 18 hours another test run was performed on the same samples.
- the relative deviations of the raw values at time t (18) from the corresponding reference values at time t (0) were determined as well as the relative deviations of the D-dimer concentration determined from the raw values.
- Table 2 shows the results from these on-board stability studies.
- Table 2 Reference at t (0) Storage closed Storage open Storage with cover device Time t [h] 0 18 18 18 Control LOW Raw values signal [mOD / min] 17.2 16.2 18.9 17.5 Relative deviation [%] -5.8% 9.9% 1.7% D-dimer concentration [ ⁇ g / L] 416 397 447 422 Relative deviation [%] -4.6% 7.5% 1.4% Control HIGH Raw values signal [mOD / min] 152.9 153.7 165.2 149.2 Relative deviation [%] 0.5% 8.0% -2.4% D-dimer concentration [ ⁇ g / L] 3638 3673 4200 3476 Relative deviation [%] 1.0% 15.4% -4.5%
- the use of the inventive cover device also achieves an improved on-board stability of the entire test. Compared with the measured raw D-dimer concentrations obtained with the open-retained reagents after 18 hours, the deviation of the test results obtained with the reagents is over the 18-hour storage with a device according to the invention were significantly lower. Due to the better preservation of the test accuracy (performance) after 18 hours of storage of the test reagents in the devices (on-board), the use of the covering device according to the invention over the open storage of the test reagents is to be preferred.
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Abstract
Description
Die Erfindung betrifft eine flexible Vorrichtung zur Abdeckung von Flüssigkeitsbehältnissen, die durch Einwirkung eines stabförmigen Objektes durchstoßbar ist und die nach Entfernung des stabförmigen Objektes wieder in ihre ursprüngliche Form zurückkehrt.The invention relates to a flexible device for covering liquid containers, which can be pierced by the action of a rod-shaped object and which returns to its original shape after removal of the rod-shaped object.
Im Bereich der modernen Diagnostik kommt eine Vielzahl von Geräten zum Einsatz, die die notwendigen Verfahrensschritte, wie z. B. Pipettieren, Mischen, Inkubieren, Zentrifugieren, Messen etc. vollautomatisch durchführen. Bei den Proben, die mit Hilfe derartiger Geräte analysiert werden, handelt es sich zumeist um menschliche oder tierische Körperflüssigkeiten oder andere Analyt-enthaltende Flüssigkeiten, die häufig mit mindestens einem Testreagenz versetzt werden müssen. Die Aufbewahrung, die Entnahme, der Transfer und die Zugabe von Flüssigkeiten, die sich in verschiedensten Behältnissen befinden können, sind also wesentliche Vorgänge im Inneren von Diagnostik-Geräten.In the field of modern diagnostics, a variety of devices is used, the necessary procedural steps, such. B. Pipetting, mixing, incubating, centrifuging, measuring etc. fully automatically perform. The samples that are analyzed using such devices are mostly human or animal body fluids or other analyte-containing fluids that often need to be spiked with at least one test reagent. The storage, removal, transfer and addition of liquids, which can be stored in various containers, are therefore essential processes inside diagnostics devices.
Ein zu berücksichtigendes Kriterium bei der Etablierung von Testen auf vollautomatischen Diagnostik-Geräten ist die Haltbarkeit der Reagenzien bei Aufbewahrung im Gerät, die sogenannte on-board Stabilität, welche maßgeblich von den Bedingungen im Gerät beeinflusst wird. Besonders problematisch ist der verdunstungsbedingte Massenverlust von Flüssigreagenzien. Zur standardisierten und zuverlässigen Bestimmung von Analyten ist die Verwendung von Reagenzien einer definierten Zusammensetzung unabdingbar, so dass durch Flüssigkeitsverluste verursachte Konzentrationsänderungen die Qualität bzw. die sogenannte Performance des gesamten Tests beeinträchtigen können. Der Grund für die Verdunstung von Flüssigreagenzien ist, dass sie für die automatischen Pipettoren direkt zugänglich sein müssen und daher in der Regel nicht hermetisch verschlossen sind.A criterion to be considered when establishing tests on fully automatic diagnostic devices is the shelf life of the reagents when stored in the device, the so-called on-board stability, which is significantly influenced by the conditions in the device. Particularly problematic is the evaporation-related mass loss of liquid reagents. For the standardized and reliable determination of analytes, the use of reagents of a defined composition is essential, so that changes in concentration caused by fluid losses can impair the quality or the so-called performance of the entire test. The reason for the evaporation of liquid reagents is that they have to be directly accessible to the automatic pipettors and therefore are not hermetically sealed as a rule.
Je nach Bauart der Geräte bzw. Pipettoren werden bekanntermaßen unterschiedliche Vorkehrungen zur Verminderung der Verdunstung von Flüssigkeiten aus den Reagenzbehältnissen getroffen. Beispielsweise verfügen viele Diagnostik-Geräte über gekühlte Halterungen bzw. Positionen, in welche die Reagenzbehälter eingesetzt werden. Durch Kühlung der Reagenzien kann der Flüssigkeitsverlust durch Verdunstung wesentlich gesenkt werden. Eine andere Maßnahme zur Verminderung von Verdunstungseffekten ist die Verringerung des Öffnungsquerschnittes des Reagenzbehältnisses, der jedoch nur in begrenztem Umfang angepasst werden kann, limitiert durch die Abmessungen des Pipettors. Ebenfalls üblich ist der Einsatz von mehr oder weniger hermetisch verschließenden Verschlusskappen oder Stopfen.Depending on the design of the devices or pipettors, it is known that various measures are taken to reduce the evaporation of liquids from the reagent containers. For example, many diagnostic devices have cooled mounts or positions into which the reagent containers are inserted. By cooling the reagents, the loss of fluid through evaporation can be significantly reduced. Another measure for the reduction of evaporation effects is the reduction of the opening cross-section of the reagent container, which, however, can be adapted only to a limited extent, limited by the dimensions of the pipettor. Also common is the use of more or less hermetically closing caps or plugs.
Einen besonders undurchlässigen Verdunstungsschutz stellen Verschlusskappen dar, die die Öffnung des Reagenzbehältnisses hermetisch abdichten, wie zum Beispiel Dreh- oder Schnappverschlüsse. Diese Art von Verdunstungsschutz ist jedoch nur für solche Geräte geeignet, die auch über eine entsprechende Einrichtung verfügen, die das Öffnen und Wiederverschließen automatisch durchführt.A particularly impervious protection against evaporation are sealing caps that hermetically seal the opening of the reagent container, such as swivel or snap closures. However, this type of evaporation protection is only suitable for those devices that also have a corresponding device that automatically performs the opening and reclosing.
Weiterhin ist die Verwendung von Verschlussstopfen, die vorzugsweise aus hochelastischen Materialien, wie z. B. Kautschuk gefertigt sind, weitverbreitet. Beispiele für derartige Vorrichtungen finden sich in EP 0 509 281 B1, EP 0 097 591 B1 und FR 27 72 727 A1. Der Vorteil dieser flexiblen Verschlussstopfen ist, dass sie über Eintrittsöffnungen für Kanülen und andere stabförmige Objekte verfügen, die durch die Elastizität des verwendeten Materials über eine gewisse Flexibilität verfügen. Dadurch können sich die Eintrittsöffnungen einerseits dem Durchmesser des eingeführten Objektes anpassen und sich andererseits nach Entfernung des Objektes wiederverschließen. Schwierigkeiten ergeben sich allerdings, wenn z. B. Pipettoren verwendet werden müssen, die einen Durchmesser aufweisen, der nur wenig geringer ist als der Öffnungsdurchmesser des Reagenzbehältnisses. In diesen Fällen muss entweder die Eintrittsöffnung so stark vergrößert werden, dass kein effektiver Verdunstungsschutz mehr gewährleistet ist, oder aber der Pipettor muss mit hohem Kraftaufwand durch eine schmale Eintrittsöffnung getrieben werden, was eine technische Anpassung des gesamten Gerätes erforderlich machen kann und außerdem durch die entstehende Reibung einen erhöhten Verschleiß verursacht. Hinzu kommt, dass derartige Verschlussstopfen, da sie zum Teil in den Hals des Reagenzgefäßes hineinragen, für jede besondere Form einer Reagenzbehältnis-Öffnung passend hergestellt werden müssen und dass eine vorgefertigte Eintrittsöffnung nur für eine begrenzte Auswahl von Pipettiervorrichtungen, und zwar solche ähnlichen Durchmessers, geeignet ist.Furthermore, the use of sealing plugs, which are preferably made of highly elastic materials, such. As rubber are made, widely used. Examples of such devices can be found in EP 0 509 281 B1, EP 0 097 591 B1 and FR 27 72 727 A1. The advantage of these flexible plugs is that they have inlet openings for cannulas and other rod-shaped objects, which have a certain flexibility due to the elasticity of the material used. As a result, on the one hand, the inlet openings can adapt to the diameter of the inserted object and, on the other hand, reseal after removal of the object. Difficulties arise, however, if z. As pipettors must be used, which have a diameter which is only slightly smaller than the opening diameter of the reagent container. In these cases, either the inlet opening must be increased so much that no more effective evaporation protection is guaranteed, or the pipettor must be driven with great force through a narrow inlet opening, which may require a technical adjustment of the entire device and also by the resulting Friction causes increased wear. In addition, such closure plugs, since they partly in the neck of the reagent vessel must suitably be prepared for any particular form of reagent container opening and that a prefabricated entry opening is suitable only for a limited range of pipetting devices, namely of such similar diameter.
Der vorliegenden Erfindung lag also die Aufgabe zugrunde, eine Vorrichtung zum Verschluss von Flüssigkeitsbehältnissen bereitzustellen, die sich dadurch auszeichnet, dass sie erstens zur Verminderung von Verdunstungseffekten und somit zu einer höheren on-board Stabilität von Flüssigreagenzien beiträgt, zweitens nahezu üniversell für verschiedenartigste Flüssigkeitsbehältnisse und Pipettiereinrichtungen in Diagnostik-Geräten eingesetzt werden kann, ohne dass Modifikationen an der Ausgestaltung der Flüssigkeitsbehältnisse selbst oder gar der Geräte erforderlich wären und drittens eine kostengünstige Alternative zu den bisher bekannten Verschlussvorrichtungen darstellt.The object of the present invention was therefore to provide a device for closing fluid containers, which firstly contributes to the reduction of evaporation effects and thus to a higher on-board stability of liquid reagents, secondly almost universally for a very wide variety of liquid containers and pipetting devices can be used in diagnostic devices without modifications to the design of the liquid containers themselves or even the devices would be required and thirdly represents a cost-effective alternative to the previously known closure devices.
Die erfindungsgemäße Lösung besteht in der Bereitstellung der in den Ansprüchen beschriebenen Gegenstände und Verfahren.The solution according to the invention is to provide the objects and methods described in the claims.
Die vorliegende Vorrichtung zur Abdeckung von Flüssigkeitsbehältnissen wird bevorzugterweise für die Abdeckung von Reagenzbehältnissen verwendet, die in Gerätenzum Einsatz kommen, welche Verfahrensschritte, wie z. B. das Pipettieren oder Mischen von Flüssigkeiten automatisch durchführen. Die Vorrichtung besteht aus einer Membran, also einer Trennschicht oder Trennlage, die sich zur Separierung zweier Teilbereiche bzw. Kompartimente eignet. Die Membran ist mit mindestens zwei strahlenförmig angeordneten Einschnitten versehen und ist bevorzugterweise auf einer Öffnung eines Flüssigkeitsbehältnisses angebracht ist, so dass dessen Öffnung vollständig abdeckt wird. In Bezug auf die vorliegende Erfindung ist der Begriff "Einschnitt" als ein Schnitt zu verstehen, der die Membran vollständig, d. h. in ihrer gesamten Dicke durchtrennt.The present device for covering liquid containers is preferably used for the cover of reagent containers used in equipment, which process steps, such as. B. perform the pipetting or mixing of liquids automatically. The device consists of a membrane, that is to say a separating layer or separating layer, which is suitable for separating two partial regions or compartments. The membrane is provided with at least two radially arranged cuts and is preferably mounted on an opening of a liquid container, so that its opening is completely covered. With regard to the present invention, the term "cut" is to be understood as a cut which completes the membrane, i. H. severed in their entire thickness.
Die Anbringung der Membran kann mit Hilfe von chemischen oder mechanischen Haftvermittlern erfolgen, die eine dichtende, fixierende Verbindung zwischen der Membran und dem Rand des Flüssigkeitsbehältnisses, der die Öffnung begrenzt, herstellen. Im Sinne der vorliegenden Erfindung ist unter chemischer Adhäsion die Haftung zu verstehen, die mit Hilfe von Klebstoffen, bevorzugterweise mit Hilfe von flüssigen Klebstoffen, zwischen zwei Fügeteilen hergestellt wird, während unter mechanischer Adhäsion die Haftung zu verstehen ist, die durch die Beschaffenheit von Oberflächen beeinflusst wird, wie z. B. die Mikroverklammerung poröser oder fasriger Oberflächen, wie z. B. Klettverschlüsse.The attachment of the membrane may be by means of chemical or mechanical adhesion promoters which provide a sealing, fixing connection between the membrane and the edge of the liquid container defining the opening. For the purposes of the present invention, the chemical adhesion is the Adhesion, which is produced by means of adhesives, preferably with the aid of liquid adhesives, between two parts to be joined, while mechanical adhesion is to be understood as adhesion, which is influenced by the nature of surfaces, such. As the micro-clamping porous or fibrous surfaces such. B. Velcro closures.
Eine bevorzugte Variante ist die Verwendung einer selbsthaftenden Membran, die auf einer Seite, zumindest in dem Bereich, der mit dem Flüssigkeitsbehältnis in direkten Kontakt gebracht werden soll, mit einem Klebstoff behandelt ist, wie es z. B. von handelsüblichen Selbstklebefolien oder Haftetiketten bekannt ist. Diese Ausführungsform hat den Vorteil, dass die selbsthaftenden Membranen auf eine Träger schicht, wie z. B. eine Schutzfolie aufgebracht werden können, von der sie leicht abgelöst werden können, ohne ihre Haftkraft zu verlieren. Um eine einfachere Handhabung der Membranen zu ermöglichen und z. B. das Ablösen selbsthaftender Membranen von einer Trägerschicht oder das Aufbringen auf ein Flüssigkeitsbehältnis zu erleichtern, kann die erfindungsgemäße Vorrichtung auch mit einer oder mehreren Abziehlaschen versehen sein.A preferred variant is the use of a self-adhesive membrane which is treated on one side, at least in the area which is to be brought into direct contact with the liquid container, with an adhesive, as z. B. of commercially available self-adhesive films or adhesive labels is known. This embodiment has the advantage that the self-adhesive membranes on a carrier layer, such. B. a protective film can be applied, from which they can be easily detached without losing their adhesive power. To allow easier handling of the membranes and z. As the detachment of self-adhesive membranes from a carrier layer or the application to a liquid container to facilitate, the inventive device may also be provided with one or more Abziehlaschen.
Eine andere Art der Anbringung der Membran ist die Verwendung einer Überwurfkappe, die die Membran mechanisch auf dem die Öffnung eines Flüssigkeitsbehältnisses begrenzenden Rand fixiert. Überwurfkappen im Sinne der vorliegenden Erfindung weisen eine bevorzugterweise kreisförmige Öffnung auf, deren Öffnungsquerschnitt die Passage des zu verwendenden stabförmigen Objektes ermöglicht. Besonders vorteilhaft ist die Verwendung von derartig gebohrten Schraubkappen, sofern das zu verschließende Flüssigkeitsbehältnis über ein Schraubgewinde verfügt. Des weiteren ist es möglich, die Membran festzukleben und zusätzlich mit Hilfe einer Überwurfkappe zu fixieren, um eine besonders stabile Befestigung zu erzielen, wodurch ein durch Reibung bedingtes Ablösen der Membran verhindert werden kann.Another type of attachment of the membrane is the use of a cap which fixes the membrane mechanically on the edge defining the opening of a liquid container. Coupling caps in the sense of the present invention have a preferably circular opening whose opening cross-section allows the passage of the rod-shaped object to be used. Particularly advantageous is the use of such drilled screw caps, if the liquid container to be closed has a screw thread. Furthermore, it is possible to adhere the membrane and additionally fix with the aid of a cap to achieve a particularly stable attachment, whereby a friction caused detachment of the membrane can be prevented.
Weiterhin kann es vorteilhaft sein, die erfindungsgemäße Vorrichtung nicht auf dem Rand des Flüssigkeitsbehältnisses selbst, sondern auf dem Rand der Überwurfkappe zu befestigen. Es ist möglich die Vorrichtung sowohl auf den äußeren Rand als auch auf dem der Innenseite der Überwurfkappe zugewendeten Rand anzubringen.Furthermore, it may be advantageous not to fasten the device according to the invention on the edge of the liquid container itself, but on the edge of the cap. It is possible to mount the device both on the outer edge and on the edge facing the inside of the cap.
Die erfindungsgemäße Vorrichtung zur Abdeckung von Flüssigkeitsbehältnissen besteht aus einer flexiblen Membran, die mit mindestens zwei Einschnitten versehen ist, welche sich in einem gemeinsamen Anfangs- bzw. Scheitelpunkt treffen, also strahlenförmig angeordnet sind.The inventive device for covering liquid containers consists of a flexible membrane, which is provided with at least two incisions, which meet in a common initial or apex, so are arranged radially.
Bei einer Membran, die mit zwei Einschnitten versehen ist, sind die beiden Einschnitte so angeordnet, dass ein Winkel von 10 ° bis 180 °, bevorzugterweise von 20 ° bis 120°, besonders bevorzugt von 45 ° bis 90 ° gebildet wird.In a membrane provided with two incisions, the two incisions are arranged so that an angle of 10 ° to 180 °, preferably from 20 ° to 120 °, particularly preferably from 45 ° to 90 ° is formed.
Je nach Durchmesser des stabförmigen Objektes und Festigkeit bzw. Elastizität des verwendeten Membranmaterials kann die Anzahl der Einschnitte und die Winkelabstände zwischen den Einschnitten so variiert werden, dass ein optimales Verhältnis zwischen Durchlassweite, minimalem Reibungswiderstand und größtmöglichem Verdunstungsschutz resultiert.Depending on the diameter of the rod-shaped object and the strength or elasticity of the membrane material used, the number of incisions and the angular intervals between the incisions can be varied so as to result in an optimum ratio between the passage width, minimum frictional resistance and the greatest possible evaporation protection.
Eine weitere bevorzugte Ausführungsform der erfindungsgemäßen Vorrichtung besteht aus einer Membran, die mit 3 bis 12, bevorzugterweise mit 4 bis 10, besonders bevorzugt mit 6 vorteilhafterweise gleich langen Einschnitten versehen ist. Es ist jedoch auch möglich, dass nicht alle Einschnitte gleich lang sind, sondern dass z. B. eine Verlängerung einiger Einschnitte- in einem bestimmten Bereich den Durchlass z. B. eines asymmetrisch verbreiterten Objektes ermöglicht.A further preferred embodiment of the device according to the invention consists of a membrane which is provided with 3 to 12, preferably with 4 to 10, particularly preferably with 6 advantageously equally long incisions. However, it is also possible that not all cuts are the same length, but that z. B. an extension of some cuts- in a certain area the passage z. B. allows an asymmetrically broadened object.
Ein Einschnitt kann mittels einer geraden, wellen- oder zackenförmigen Schnittführung ausgeführt sein. Bevorzugterweise sind die Einschnitte gleichwinklig zueinander angeordnet, so dass mehrere gleichschenklige Dreiecke entstehen, deren Grundseiten mit dem umlaufenden Rand der Membran verbunden sind. Die Länge der vom Scheitelpunkt ausgehenden Einschnitte kann variiert werden und wird bevorzugterweise so gewählt, dass dem Bereich des stabförmigen Objektes, welcher über den größten Durchmesser verfügt und welcher noch die Abdeckungsvorrichtung durchstoßen soll, Durchlass geboten wird.An incision can be made by means of a straight, wavy or serrated cut. Preferably, the incisions are arranged equiangularly to each other, so that a plurality of isosceles triangles arise whose bases are connected to the peripheral edge of the membrane. The length of the incisions originating from the vertex can be varied and is preferably chosen so that the region of the rod-shaped object which has the largest diameter and which is still intended to penetrate the covering device is provided with passage.
Die erfindungsgemäße Vorrichtung ist durch Einwirkung eines stabförmigen Objektes durchstoßbar und kehrt nach Entfernung des stabförmigen Objektes wieder in ihre ursprüngliche Form zurück. Durch Einwirkung beispielsweise eines Pipettors werden die freien Enden der Dreiecke, die in die Membran eingeschnitten sind, in das Innere des Flüssigkeitsbehältnisses verdrängt, wodurch eine Öffnung ensteht, die sich flexibel, d. h. reibungsarm dem Durchmesser des Pipettors anpasst. Nach Entfernung des Pipettors nehmen die Membrandreiecke aufgrund der Elastizität des verwendeten Materials wieder ihre ursprüngliche Position ein und verschließen somit die Öffnung des Flüssigkeitsbehältnisses. Dieser Vorgang ist vielmalig wiederholbar.The device according to the invention can be pierced by the action of a rod-shaped object and returns to its original shape after removal of the rod-shaped object. Become by the action of, for example, a pipettor the free ends of the triangles, which are cut into the membrane, displaced into the interior of the liquid container, whereby an opening is ensteht, which adapts flexibly, ie with low friction to the diameter of the pipettor. After removal of the pipettor, the membrane triangles return to their original position due to the elasticity of the material used and thus close the opening of the liquid container. This process is repeatable many times.
Stabförmige Objekte im Sinne der vorliegenden Erfindung sind zum Beispiel Vorrichtungen zum Transfer von Flüssigkeiten, wie Pipettoren oder Kanülen oder auch Vorrichtungen zum Mischen von Flüssigkeiten, wie zum Beispiel Rührstäbe, und sind in der Regel zylindrisch oder konisch-geformt. Das Ende derartiger stabförmiger Objekte kann spitz, abgerundet oder stumpf ausgestaltet sein.Rod-shaped objects for the purposes of the present invention are, for example, devices for transferring liquids, such as pipettors or cannulas, or devices for mixing liquids, such as stirring rods, and are generally cylindrical or conical-shaped. The end of such rod-shaped objects may be pointed, rounded or blunt.
Die flexible Membran besteht bevorzugterweise aus einem elastischen, dampfundurchlässigen Material. Bei der Auswahl des Membranmaterials sollte der Fachmann selbstverständlich berücksichtigen, dass für die Abdeckung von Flüssigkeitsbehältnissen, die so verschiedene Flüssigkeiten wie z. B. wässrige Lösungen oder organische Lösungsmittel enthalten können, ein adäquates Membranmaterial verwendet wird, welches durch die abzudeckende Flüssigkeit oder deren Dämpfe nicht beeinträchtigt wird. Besonders bevorzugt besteht die Membran aus einem Material der Gruppe Polyethylen (PE), Polypropylen (PP), Polyethylenterephthalat (PET), Polystyrol (PS), Polyamid (PA), Polybutylentherephthalat (PBT), Polycarbonat, (PC), Polyimiden (PI), Naturkautschuk, Silikon-, Brombutyl- und Chlorbutylkautschuk. Ebenso eignen sich Membranen, die aus Mischungen dieser Materialien oder aus mindestens zwei verschiedenartigen Schichten dieser Materialien bestehen. Weiterhin ist es möglich, z. B. eine Celluloseschicht mit einer Schicht von elastischem Material zu kombinieren.The flexible membrane preferably consists of an elastic, vapor-impermeable material. When selecting the membrane material, the expert should of course take into account that for the cover of liquid containers, the so different liquids such. As aqueous solutions or organic solvents, an adequate membrane material is used, which is not affected by the liquid to be covered or their vapors. Particularly preferably, the membrane consists of a material from the group polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polystyrene (PS), polyamide (PA), polybutylene terephthalate (PBT), polycarbonate, (PC), polyimides (PI) , Natural rubber, silicone, bromobutyl and chlorobutyl rubber. Likewise suitable are membranes which consist of mixtures of these materials or of at least two different layers of these materials. Furthermore, it is possible, for. B. to combine a cellulosic layer with a layer of elastic material.
Die Dicke der flexiblen Membran ist bevorzugterweise nicht größer als 150 µm und liegt vorteilhafterweise zwischen 40 µm und 100 µm, besonders bevorzugt zwischen 50 µm und 80 µm.The thickness of the flexible membrane is preferably not greater than 150 μm and is advantageously between 40 μm and 100 μm, more preferably between 50 μm and 80 μm.
Eine weitere besondere Ausführungsform der erfindungsgemäßen Vorrichtung ist dadurch gekennzeichnet, dass sich im Scheitelpunkt der strahlenförmig angeordne ten Einschnitte eine kreisförmige, ovale oder polygonale Öffnung befindet, die z. B. durch Ausstanzen geschaffen werden kann. Vorteilhafterweise entspricht der Durchmesser dieser Öffnung dem Durchmesser desjenigen Teils des stabförmigen Objekts, welcher beim Eintritt in das Flüssigkeitsbehältnis zuerst und beim Austritt zuletzt die Verschlussvorrichtung passiert, so dass z. B. Flüssigkeitsreste, die der Außenseite eines Pipettors anhaften, an der Membran abgestreift werden. Auf diese Weise kann eine übermäßige Verunreinigung der Verschlussvorrichtung vermieden werden, wodurch die Gefahr einer Vermischung von z. B. verschiedenen Reagenzien vermindert ist.Another particular embodiment of the device according to the invention is characterized in that arranged at the apex of the radiating th incisions is a circular, oval or polygonal opening, the z. B. can be created by punching. Advantageously, the diameter of this opening corresponds to the diameter of that part of the rod-shaped object which passes first when entering the liquid container and at the exit last the closure device, so that z. B. liquid residues that adhere to the outside of a pipettor are stripped on the membrane. In this way, excessive contamination of the closure device can be avoided, whereby the risk of mixing of z. As different reagents is reduced.
In Figur 1 sind verschiedene Ausführungsformen der erfindungsgemäßen Vorrichtung zur Abdeckung von Flüssigkeitsbehältnissen in einer Aufsicht dargestellt. Die Vorrichtung besteht aus einer elastischen Membran (1), die mit mindestens zwei Einschnitten (2) versehen ist, welche strahlenförmig angeordnet sind. Fig. 1 a und Fig. 1 b zeigen erfindungsgemäße Vorrichtungen, die mit jeweils sechs Einschnitten (2) versehen sind. Durch die gleichwinkelige Anordnung der Einschnitte entstehen jeweils sechs gleichschenklige Dreiecke (3), deren Grundseiten mit dem umlaufenden Rand der Membran verbunden sind. Die Vorrichtung in Fig. 1 b verfügt im Scheitelpunkt der strahlenförmig angeordneten Einschnitte über eine kreisförmige Öffnung (4). Die Vorrichtungen in Fig. 1 a und b sind mit jeweils drei Abziehlaschen (5) versehen, die durch entsprechenden Zuschnitt der Membran ausgestaltet sind und die die Handhabung der Vorrichtungen erleichtern. Fig. 1 c zeigt eine erfindungsgemäße Vorrichtung, die mit zwei Einschnitten versehen ist, die so angeordnet-sind, dass sie einen Winkel (6) von etwa 70 ° bilden. Fig. 1d zeigt eine erfindungsgemäße Vorrichtung, die mit sechs Einschnitten versehen ist, wobei die Einschnitte nicht alle gleich lang sind. Die Form bzw. der Umriss der Vorrichtungen richtet sich nach der Form der abzudeckenden Öffnung des Flüssigkeitsbehältnisses. Während sich die Vorrichtungen der Figuren 1 a bis c besonders zur Abdeckung von kreisrunden Öffnungen eignen, kann eine Vorrichtung mit einer Form wie in Fig. 1 d gezeigt zur Abdeckung von ovalen Öffnungen verwendet werden. Fig. 1d verdeutlicht weiterhin, dass der durch die Einschnitte durchstoßbar gemachte Bereich der Membran nicht im Zentrum der Vorrichtung liegen muss, sondern auch an einer anderen als der zentralen Position platziert werden kann.FIG. 1 shows various embodiments of the device according to the invention for covering liquid containers in a plan view. The device consists of an elastic membrane (1), which is provided with at least two incisions (2), which are arranged radially. Fig. 1 a and Fig. 1 b show devices according to the invention, which are each provided with six incisions (2). The equiangular arrangement of the incisions each produce six isosceles triangles (3) whose bases are connected to the peripheral edge of the membrane. The device in Fig. 1 b has at the apex of the radially arranged incisions via a circular opening (4). The devices in Fig. 1 a and b are provided with three pull tabs (5), which are designed by appropriate cutting of the membrane and facilitate the handling of the devices. Fig. 1 c shows a device according to the invention provided with two cuts arranged to form an angle (6) of about 70 °. Fig. 1d shows a device according to the invention, which is provided with six incisions, wherein the incisions are not all the same length. The shape or the outline of the devices depends on the shape of the opening of the liquid container to be covered. While the devices of Figures 1 a to c are particularly suitable for covering circular openings, a device having a shape as shown in Figure 1 d can be used to cover oval openings. Fig. 1d further illustrates that the area of the membrane rendered pierceable by the sipes need not be in the center of the device, but can also be placed at a position other than the central position.
Figur 2 veranschaulicht die Anbringung einer erfindungsgemäßen Vorrichtung zur Abdeckung von Flüssigkeitsbehältnissen (7), welche in diesem Beispiel mit einem Schraubgewinde (8) ausgestattet sind und für die eine gebohrte Schraubkappe (9) mit einer zentralen, kreisrunden Öffnung zur Verfügung steht. Fig. 2a zeigt, dass die erfindungsgemäße Vorrichtung direkt auf den die Öffnung des Flüssigkeitsbehältnisses begrenzenden Rand (10) aufgebracht werden kann. Die Fixierung der Membran kann durch Haftvermittler, wie z. B. einen Klebstoff auf der Auflagefläche, bewirkt werden, durch die mechanische Befestigung durch Aufschrauben der Schraubkappe oder durch eine Kombination von beidem. Fig. 2b zeigt, dass die erfiridungsgemäße Vorrichtung zur Abdeckung auch auf die Aussenseite des die Öffnung der Schraubkappe begrenzenden Randes aufgebracht werden kann, wobei die Membran in diesem Fall vorzugsweise mit Hilfe eines Haftvermittlers befestigt wird.Figure 2 illustrates the attachment of a device according to the invention for covering liquid containers (7), which in this example are provided with a screw thread (8) and for which a drilled screw cap (9) with a central, circular opening is available. Fig. 2a shows that the device according to the invention can be applied directly to the edge of the opening of the liquid container (10). The fixation of the membrane can be achieved by adhesion promoters such. As an adhesive on the support surface, caused by the mechanical attachment by screwing the screw cap or by a combination of both. 2b shows that the device according to the invention for covering can also be applied to the outside of the edge defining the opening of the screw cap, the membrane in this case preferably being fastened with the aid of a bonding agent.
Figur 3 veranschaulicht die Zweckdienlichkeit einer erfindungsgemäßen Vorrichtung (1), die in diesem Fall aus einer elastischen Membran besteht, die mit sechs Einschnitten versehen ist und auf der Öffnung einer Überwurfkappe (11) aufgebracht ist, welche wiederum der Öffnung eines Flüssigkeitsbehältnisses (12) aufsitzt. Die Füllstandhöhe der Flüssigkeit im Inneren des Behältnisses ist durch eine gestrichelte Linie angedeutet. Fig. 3a zeigt, wie ein Pipettor (13), der entlang seiner Längsachse über Bereiche verschiedenen Durchmessers verfügt, mit der Spitze, d. h. mit dem Bereich des geringsten Durchmessers (14) die erfindungsgemäße Vorrichtung durchstößt. Fig. 3b und Fig. 3c zeigen, wie durch den zunehmenden Aussendurchmesser (15, 16) des Pipettors, die freien Enden der Membrandreiecke (3) in das Innere des Behältnisses verdrängt werden, wodurch sich die Öffnung dem jeweiligen Aussendurchmesser des Pipettors flexibel anpasst.Figure 3 illustrates the expediency of a device (1) according to the invention, which in this case consists of an elastic membrane provided with six cuts and applied to the opening of a cap (11), which in turn rests on the opening of a liquid container (12) , The level of the liquid inside the container is indicated by a dashed line. FIG. 3a shows how a pipettor (13), which has regions of different diameter along its longitudinal axis, pierces the device according to the invention with the tip, ie with the region of the smallest diameter (14). 3b and 3c show how, as a result of the increasing outer diameter (15, 16) of the pipettor, the free ends of the membrane triangles (3) are displaced into the interior of the container, whereby the opening flexibly adapts to the respective outer diameter of the pipettor.
Die im folgenden beschriebenen Beispiele dienen der exemplarischen Beleuchtung einzelner Aspekte dieser Erfindung und sind nicht als Einschränkung zu verstehen.The examples described below are intended to exemplify aspects of this invention, and are not intended to be limiting.
Es wurden vergleichende Untersuchungen anhand von drei Reagenzien durchgeführt, die für ein turbidimetrisches Testverfahren zur quantitativen Bestimmung von quervernetzten Fibrinderivaten, die die D-Dimer Domäne enthalten (im folgenden abgekürzt als D-Dimer), verwendet werden können. Bei allen drei Reagenzien handelt es sich um wässrige Lösungen, die zur Durchführung des Tests mit einer Plasmaprobe vermischt werden. Während es sich bei Reagenz B um eine Suspension von Latexpartikeln handelt, die mit einem D-Dimer-spezifischen, monoklonalen Antikörper beschichtet sind (siehe z. B. EP 0 122 478-B2), handelt es sich bei den Reagenzien A und C im wesentlichen um gepufferte Salzlösungen. Bei Anwesenheit von D-Dimer in einer Plasmaprobe findet eine Agglutination der Latexpartikel statt, die anhand der Trübung quantifiziert werden kann. Dieses Testverfahren wurde auf dem automatischen Gerinnungsanalyzer Sysmex® CA-560 (Dade Behring Marburg GmbH, Marburg, Deutschland) zur automatischen Abarbeitung etabliert.Comparative studies were performed on three reagents that can be used for a turbidimetric assay for the quantitative determination of cross-linked fibrin derivatives containing the D-dimer domain (hereinafter abbreviated as D-dimer). All three reagents are aqueous solutions that are mixed with a plasma sample to perform the assay. While reagent B is a suspension of latex particles coated with a D-dimer specific monoclonal antibody (see, for example, EP 0 122 478-B2), reagents A and C are known in the art essentially to buffered saline solutions. In the presence of D-dimer in a plasma sample, agglutination of the latex particles occurs, which can be quantified by turbidity. This test procedure was established on the automatic coagulation analyzer Sysmex® CA-560 (Dade Behring Marburg GmbH, Marburg, Germany) for automatic processing.
Der Sysmex® CA-560 Analyzer (kurz: CA-560) verfügt über eine temperierbare Position (15 ± 1°C) für ein Testreagenzbehältnis und weitere Positionen für Reagenzbehältnisse, deren Temperatur nicht reguliert werden kann und demzufolge der Raumtemperatur (ca. 15 bis 25°C) entsprechen. Testreagenz A wurde in der temperierten Position platziert, während die Testreagenzien B und C in nicht-temperierten Positionen platziert wurden. Bei den Reagenzbehältnissen handelte es sich um 5 ml Gewindeflaschen aus Glas mit einem Öffnungsdurchmesser von etwa 11 mm.The Sysmex® CA-560 Analyzer (CA-560 for short) has a temperature-controllable position (15 ± 1 ° C) for a test reagent container and other reagent container positions that can not be adjusted for temperature and therefore at room temperature (approx 25 ° C). Test reagent A was placed in the tempered position while test reagents B and C were placed in non-tempered positions. The reagent containers were 5 ml glass threaded bottles with an opening diameter of about 11 mm.
Zum Zeitpunkt t(0) wurden die Reagenzbehältnisse A, B und C geöffnet und in den vorgesehen Positionen des CA-560 platziert, entweder mit oder ohne Verwendung einer erfindungsgemäßen Abdeckungsvorrichtung. In der vorliegenden Untersuchung wurde eine selbsthaftende Polypropylenmembran verwendet, die auf der einen Seite mit Cellulose beschichtet und auf der anderen Seite mit einem Klebstoff behandelt war, so dass sich eine Gesamtfoliendicke von 62 µm und ein Gewicht von 93 g/qm ergab. Die Membranen waren kreisrund zugeschnitten, verfügten über einen Durchmesser von etwa 12 mm und waren mit 8 radialen, gleichwinklig zueinander angeordneten und gleich langen Einschnitten versehen. Die Membranen wurden auf die oberen Ränder der Reagenzbehältnisse geklebt und zusätzlich mit einer gebohrten Schraubkappe stabilisiert, wie auch in Fig. 2a dargestellt.At time t (0), reagent containers A, B and C were opened and placed in the designated positions of the CA-560, either with or without the use of a capping device according to the present invention. In the present study, a self-adhesive polypropylene membrane was used, which was coated on one side with cellulose and treated on the other side with an adhesive was, so that a total film thickness of 62 microns and a weight of 93 g / qm resulted. The membranes were circular cut, had a diameter of about 12 mm and were provided with 8 radial, equiangularly arranged and equally long incisions. The membranes were glued to the upper edges of the reagent containers and additionally stabilized with a drilled screw cap, as also shown in Fig. 2a.
Jedes der Reagenzbehältnisse enthielt zum Zeitpunkt t(0) 2 ml Reagenzflüssigkeit. Eine Massenbestimmung der befüllten Reagenzbehältnisse wurde zum Zeitpunkt t(0) und nach 18 Stunden, zum Zeitpunkt t(18) durchgeführt. Aus der Differenz (Δ) der Masse zum-Zeitpunkt t(0) und der Masse zum Zeitpunkt t(18) wurde der relative Massenverlust der Reagenzflüssigkeiten ermittelt.Each of the reagent containers contained 2 ml of reagent liquid at time t (0). A mass determination of the filled reagent containers was carried out at time t (0) and after 18 hours, at time t (18). The relative mass loss of the reagent liquids was determined from the difference (Δ) of the mass at time t (0) and the mass at time t (18).
Anhand der Ergebnisse, die in Tabelle 1 zusammengefasst sind, wird deutlich, dass durch die Verwendung einer erfindungsgemäßen Vorrichtung zur Abdeckung der Reagenzbehältnisse eine Senkung von verdunstungsbedingten Masseverlusten um 30 bis 50 % erzielt werden kann.
Zur Untersuchung der on-board Stabilität wurden wieder die Testreagenzien A, B und C, die sich zur quantitativen Bestimmung von D-Dimer eignen, in die vorgesehenen Positionen des CA-560 eingesetzt (siehe Beispiel 1), und es wurden unterschiedliche Versuchsreihen unter folgenden Testbedingungen durchgeführt:
- 1) Die drei Reagenzbehältnisse wurden nur für den Zeitraum der Testdurchführung manuell geöffnet und bis zum nächsten Durchlauf mit einem integralen Stopfen und einer Schraubkappe versehen verschlossen aufbewahrt.
- 2) Die drei Reagenzbehältnisse wurden über den gesamten Versuchszeitraüm offen aufbewahrt.
- 3) Die drei Reagenzbehältnisse, welche die Testreagenzien enthielten, wurden mit einer wie in
Beispiel 1 beschriebenen erfindungsgemäßen Verschlussvorrichtung versehen.
- 1) The three reagent containers were opened manually only for the period of the test procedure and kept sealed until the next run with an integral stopper and a screw cap.
- 2) The three reagent containers were kept open throughout the experimental period.
- 3) The three reagent containers containing the test reagents were provided with a closure device according to the invention as described in Example 1.
Zum Zeitpunkt t(0) wurden die Reagenzbehältnisse, die jeweils 2 ml Reagenzflüssigkeit enthielten, erstmalig geöffnet, in den CA-560 eingebracht, und es wurde zum Zeitpunkt t(0) ein Test zur quantitativen Bestimmung von D-Dimer in einer Plasmaprobe niedriger D-Dimer-Konzentration (Kontrolle LOW) und in einer Plasmaprobe hoher D-Dimer-Konzentration (Kontrolle HIGH) durchgeführt. Für jede Probe wurde ein Rohwert (mOD/min) gemessen, anhand dessen aus einer zuvor erstellten Kalibrationskurve, die D-Dimer-Konzentration der gemessenen Probe bestimmt werden konnte. Der Rohwert, der zum Zeitpunkt t(0) bestimmt wurde, diente im weiteren als Referenzwert für die Performance des Testes. Die Reagenzien wurden unter den in 1), 2) oder 3) beschriebenen Bedingungen in den Geräten aufbewahrt und nach 18 Stunden wurde ein weiterer Testdurchlauf mit den gleichen Proben durchgeführt. Es wurden die relativen Abweichungen der Rohwerte zum Zeitpunkt t(18) von den korrespondierenden Referenzwerten zum Zeitpunkt t(0) ermittelt, wie auch die relativen Abweichungen der D-Dimer-Konzentration ermittelt wurden, die anhand der Rohwerte bestimmt worden waren.At time t (0), the reagent containers, each containing 2 ml of reagent liquid, were first opened, placed in the CA-560, and at time t (0), a test for quantitative determination of D-dimer in a lower D plasma sample -Dimer concentration (control LOW) and performed in a plasma sample of high D-dimer concentration (control HIGH). For each sample, a raw value (mOD / min) was measured, from which a previously prepared calibration curve could be used to determine the D-dimer concentration of the measured sample. The raw value, which was determined at time t (0), further served as the reference value for the performance of the test. The reagents were stored in the equipment under the conditions described in 1), 2) or 3), and after 18 hours another test run was performed on the same samples. The relative deviations of the raw values at time t (18) from the corresponding reference values at time t (0) were determined as well as the relative deviations of the D-dimer concentration determined from the raw values.
Tabelle 2 zeigt die Ergebnisse aus diesen Untersuchungen zur on-board Stabilität.
Wie aus Tabelle 2 hervorgeht, wird durch die Verwendung der erfindungsgemäßen Abdeckungsvorrichtung auch eine verbesserte on-board Stabilität des gesamten Testes erzielt. Verglichen mit den gemessenen Rohwerten bzw. den ermittelten D-Dimer-Konzentrationen, die mit Hilfe der offen aufbewahrten Reagenzien nach 18 Stunden gewonnen wurden, ist die Abweichung der Testergebnisse, die mit den Reagenzien gewonnen wurden, die über die 18stündige Aufbewahrung mit einer erfindungsgemäßen Vorrichtung abgedeckt waren, wesentlich geringer. Aufgrund der besseren Erhaltung der Testgenauigkeit (Performance) nach 18stündiger Aufbewahrung der Testreagenzien in den Geräten (on-board) ist die Verwendung der erfindungsgemäßen Abdeckungsvorrichtung gegenüber der offenen Aufbewahrung der Testreagenzien zu bevorzugen.As is apparent from Table 2, the use of the inventive cover device also achieves an improved on-board stability of the entire test. Compared with the measured raw D-dimer concentrations obtained with the open-retained reagents after 18 hours, the deviation of the test results obtained with the reagents is over the 18-hour storage with a device according to the invention were significantly lower. Due to the better preservation of the test accuracy (performance) after 18 hours of storage of the test reagents in the devices (on-board), the use of the covering device according to the invention over the open storage of the test reagents is to be preferred.
Claims (18)
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DE102004052082A DE102004052082A1 (en) | 2004-10-26 | 2004-10-26 | Pierceable, flexible device for covering liquid containers |
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EP1652787A1 true EP1652787A1 (en) | 2006-05-03 |
EP1652787B1 EP1652787B1 (en) | 2008-03-12 |
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EP05022082A Not-in-force EP1652787B1 (en) | 2004-10-26 | 2005-10-11 | Piercable flexible device for closing a container for liquid |
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US (1) | US20060088446A1 (en) |
EP (1) | EP1652787B1 (en) |
JP (1) | JP2006124035A (en) |
AT (1) | ATE388904T1 (en) |
CA (1) | CA2524314A1 (en) |
DE (2) | DE102004052082A1 (en) |
ES (1) | ES2300919T3 (en) |
Cited By (7)
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WO2008068663A1 (en) | 2006-12-01 | 2008-06-12 | Koninklijke Philips Electronics N. V. | Needle interface for fluid connections |
EP1906188A3 (en) * | 2006-09-27 | 2010-01-20 | FUJIFILM Corporation | Liquid circulating apparatus and measurement apparatus |
DE102012007887A1 (en) * | 2012-04-23 | 2013-10-24 | Erwin Quarder Systemtechnik Gmbh | Sample vessel i.e. multi-corrugated board, for examination of e.g. biological cell sample, has closure unit returning back into closed position from open position by return forces after termination of force by opening unit |
GB2504300A (en) * | 2012-07-24 | 2014-01-29 | Genevac Ltd | Apparatus and method for evaporating a solvent from a sample |
WO2014072170A1 (en) * | 2012-11-06 | 2014-05-15 | Gerhard Bonecker | Test set for a photometric measuring device, and photometric measuring method for a sample liquid |
EP3563929A1 (en) * | 2018-04-30 | 2019-11-06 | Firmenich SA | Apparatus for customized production of a flavoring agent mix |
CN113474083A (en) * | 2019-01-04 | 2021-10-01 | 仪器实验室公司 | Container stopper for high puncture count applications |
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GB201012494D0 (en) * | 2010-07-26 | 2010-09-08 | Randox Lab Ltd | Reagent bottles, valves thereof, washing modules and methods and apparatus for dispensing reagents |
JP6294735B2 (en) * | 2013-04-05 | 2018-03-14 | 協和メデックス株式会社 | Reagent bottle cap and reagent container |
CN114789843B (en) * | 2022-04-24 | 2022-11-22 | 四川先通原子医药科技有限公司 | Container for radioactive particles and use thereof |
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CN113474083A (en) * | 2019-01-04 | 2021-10-01 | 仪器实验室公司 | Container stopper for high puncture count applications |
Also Published As
Publication number | Publication date |
---|---|
US20060088446A1 (en) | 2006-04-27 |
CA2524314A1 (en) | 2006-04-26 |
DE102004052082A1 (en) | 2006-04-27 |
DE502005003180D1 (en) | 2008-04-24 |
EP1652787B1 (en) | 2008-03-12 |
ATE388904T1 (en) | 2008-03-15 |
ES2300919T3 (en) | 2008-06-16 |
JP2006124035A (en) | 2006-05-18 |
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