GB2570061B - Adhesive film for de-capping tubes and multiwell plates - Google Patents

Description

ADHESIVE FILM FOR DE-CAPPING TUBES AND MULTIWELL PLATES

Field of the Invention

The present invention relates adhesive films suitable for use in a method for de-capping capped tubes in an array.

Background

Multwell plates and/or cluster tube racks comprising a plurality of tubes or wellsarranged in an array are used in a wide variety of test procedures and for storage ofsamples. These plates, also known as microplates, and racks of tubes are also usedin the storage of chemical compounds. In addition, other fields of research have theneed for storage of small amounts of materials these are also well-suited for this typeof tube array. For example, biology and medical researchers often have the need forlong term storage of small volumes of biological materials such as bacterial, fungal,viral, chemical compounds or DNA samples, to name just a few. Many researchinstitutions amass large libraries of samples and controls and may make suchmaterials available to other researchers. Forensic laboratories and particularly lawenforcement agencies have the need to retain evidence for long periods of times,which evidence often includes biological specimens, such as tissue, blood or otherspecimens for DNA testing. Industrial applications for such capabilities include theretention of standards for quality control and samples for batch tracking. There aretherefore a wide range of applications across virtually every scientific discipline thatbenefit from the ability to store a large number of small samples in arrays of tubes orvials.

The process of analyzing chemical and biological samples may involve thousands ofdifferent samples and the demand for this type of analysis has led to the developmentof robotic laboratory automation systems. Modem robotic handling methods and othermodem technologies mean that only very small aliquots of material are now requiredin many experiments and therefore small storage containers, such as compoundstorage vials, can be used to collect and store chemical and biological compounds.These are often stored in vast compound or sample libraries containing many thousands, if not millions, of samples. The scale of such operations inevitably meansthat these storage containers have to be handled robotically.

The vials are normally kept in a rack or support specially designed for the storage andtransportation of such vials. These racks come in vasying sizes and hold a varyingquantity of vials. A typical rack may hold an 8 x 12 array of 96 vials, or384 vials in a16 x 24 array. The vial size will depend on the required aliquot. Once al! of the vials inthe rack are filled with chemicals, the racks may be stacked one upon another, orstored in special storage trays, and placed in a storage area often at low temperature.Dozens of these 96 vial racks may be used for collecting the chemical compoundsfrom a single experiment and may need to be kept for future evaluations. Racks thatcontain hundred of vials which hold only microlitres of solution are also available, aswell as racks that hold only a. few vials that contain several millilitres.

For storage and transportation of the racks, and to protect the chemical compoundsfrom contamination or spillage, the vials are typically capped or sealed. Caps for thispurpose may be of the screw cap type or may be a push fit. Push fit caps are generallymade from a non reactive, compliant plastic material. These push fit caps are pressedinto the top of the vial or in some cases, onto and over the top of the vial. Both typesof caps preferably form an air tight seal that protects the contents of the vials from theexternal environment and eliminate loss of the chemical compound. The caps alsoallow the racks to be stacked without compromising the chemical compounds withinthe vials.

The application and removal of screw caps from vials is both time consuming andexpensive (see below) and the present invention is not directed at the removal of screwcaps, but rather at the removal of caps of the push fit variety.

An alternative method of sealing contents within an array of wells or vials is to heatseal them with a peelable sealing sheet, typically made from plastic or plastic coatedaluminium foil. Heat sealing systems for this purpose are commercially available, suchas the Eppendorf Heat Sealerfrom Eppendorf AG, Barkhausenweg 1 22339 Hamburg,Germany. Simple adhesive backed sealing sheets are also available.

When access to the contents of the viais is required, this can be achieved by peelingback the sheet from the entire plate, or by piercing the seal, which can subsequentlybe re-sealed by applying a new sheet of sealing material over the pierced seal. Thisprocess of piercing and re-sealing may be repeated multiple times. A device and method for removing these sheet or film seals is described in EP21186693 (Nexus Biosystems, Inc). However, this device and method is limited toremoving a peelable film seal from an array of vials or wells.

When access to the contents of a capped vial or vials is required there is a need for aquick, reliable and convenient system and method for removing caps from an array ofvials. Manual removal can be time consuming and may even be impractical where thenumber of vials involved is large. Although automated de-capping systems andmethods for removing screw caps do exist, such as those described in US 7,421,831(Nexus Biosystems, inc.), in order to operate effectively these methods require theuse of very specific gripping machines and specially designed caps, all designed andmanufactured to very close tolerances. Since vast stores and libraries of capped tubesalready exist, where the caps are not of this type and in fact are not necessarily of anyone particular consistent design within a library, such methods are not practical oreconomic.

It is an object of the present invention to overcome or mitigate the problems outlinedabove and to provide a simple, inexpensive system and method for de-capping tubescapped with a wide variety of caps.

Summary of the Invention

According to a first aspect there is provided an adhesive film suitable for use in amethod for de-capping capped tubes in an array, said adhesive film incorporating oneor more apertures in the adhesive film enabling a robot machine to engage with theadhesive film once sealed to the tube caps in order to peel away the tube caps fromthe tubes in the array.

In an example, the aperture(s) are located substantially at or towards an end of theadhesive film.

In an example, the aperture(s) are located substantially at or towards a side of theadhesive film.

Also described is a method of de-capping capped tubes in a microplate array. Forexample there is described a method of de-capping capped tubes in a microplate/tuberack array said method comprising the steps of:- (i) placing a microplate array of capped tubes into an adhesive filmapplication device; (ii) applying an adhesive film onto the top of the array of tube caps; (iii) applying an upward force on the film, away from the plane of themicroplate array, to peel the tube caps away from the tubes, complete with the film towhich the tube caps are attached, thus separating the tube caps from the tubes.

By using an adhesive film such as a heat sealable adhesive film of the type that isused as an alternative method to caps for sealing tubes/vials, the adhesive film formsa strong bond to the exposed tops of the tube caps, and the caps can be pulled awayfrom the tubes, the film and caps ultimately being discarded. The adhesive filmapplication device may therefore take the form of a conventional heat sealer. Heatsealable films are commercially available in rolls and in individual sheets. It will beunderstood that the adhesive film used in this method has an adhesive surface havinga width substantially the same or greater than the width of the tube array, and a lengthsubstantially the same or greater than the length of the tube array.

Accordingly, preferably the adhesive film comprises a heat sealable film. By using aheat sealable film that is compatible with the material from which the caps are made,and the appropriate time and temperature for the heat sealing operation, the film canbe made to form a substantially permanent weld seal to the exposed tops of the tubecaps in the tube array. It is then possible to peel the film away from the tube arraybringing with it the tube caps. An example of this materia! compatibility is where thecaps are made from a material containing polypropylene and the heat sealable filmincludes a polypropylene containing layer on the side of the film that is placed againstthe top of the caps. Many thermoplastics or thermosoftening plastics can be used toform a substantially permanent weld seal in this application, depending on the composition of the caps. A wide variety of heat sealable films and foils are alreadycommercially available and well known to those skilled in the heat sealing process.

Accordingly preferably the adhesive film forms a substantially permanent weld seal tothe top of the tube caps in the array. Suitable film or foil to make a substantiallypermanent weld to a particular type of tube cap may be determined by a materialsexpert, or by experimentation.

Preferably the adhesive film includes a backing layer for additional strength. Suitablebacking layers include films such as Polyester film, or foils such as aluminium foil.

Preferably the adhesive film includes a foil layer for additional strength.

Preferably the adhesive film includes a heat stable polymer layer such as a PolyesterSayer for additional strength.

Preferably the sheet of adhesive film used in step (ii) of the method comprises a pre-cut sheet. Preferably the adhesive film used in step (ii) is derived from a roll or web ofadhesive film. The choice will depend largely on the type of sealing machine beingused in the de-capping process. Where a roll or web of adhesive film is being usedthis is preferably pre-perforated for easy division into sheets before or during thesealing process or cut into suitable lengths within the sealing machine.

Preferably the adhesive film used in step (ii) comprises a pre-cut strip of adhesive film.

Preferably the adhesive film used in step (ii) is derived from a roll or web of adhesivefilm.

Preferably the roll or web of adhesive film is pre-perforated for easy division into sheetsbefore or during the sealing process.

There is also described a device or apparatus for de-capping capped tubes in amicroplate/tube rack array using the method as claimed and described herein. Forexample there is described an apparatus for decapping capped tubes in amicroplate/tube rack array, said apparatus comprising:- (a) a transport system for transporting a microplate/tube rack array ofcapped tubes; (b) an adhesive film application station at which an adhesive film is appliedover the top of the array of caps; (c) a holding means adapted to hold down a microplate/tube rack in orderto resist an upward force applied to the film: (d) a de-capping station at which an upward force is applied to the film/capcombination in order to separate the film/cap combination from the de-capped tubes,which remain in their array; (e) a disposal means for disposing of the unwanted film/cap combination.

The apparatus may be microprocessor controlied or be controlled manually by anoperator.

Brief Description of the Drawings

Preferred embodiments of the present invention will now be described by way ofexample only with reference to the accompanying figures wherein:-

Figure 1 illustrates an array of 96 tubes in a micropiate;

Figure 2 illustrates caps inserted into the tubes of Figure 1 to give an array of 96capped tubes;

Figure 3 illustrates an adhesive film strip applied onto the exposed tops of the caps ofthe capped tubes of Figure 2;

Figure 4 illustrates the adhesive film shown in Figure 3 in the process of being peeledaway from the tube array complete with the caps adhered to the film;

Figure 5 illustrate a detail at the bottom of a tube showing how a tube locks into a plateto prevent rotation.

Detailed Description

Figure 1 illustrates a multiwell plate 10 containing an 8 x 12 array of 96 individualtubes, wells or vials 11 retained in microplate rack or tube rack 12. In this context the terms "tube", "vial" and "well" all have a similar meaning and refer to sample holdingcontainers designed to be stored or contained in a multiwell rack. In various possiblearrangements these wells may be individual, connected together in strips or integralwith microplate rack itself. A wide variety of storage tubes designs are already available on the market. Where atube is designed to take a screw cap the tube may include one or more fins aroundthe bottom of the tube which engage in corresponding feature(s) in the rack to preventrotation of the tube as the cap is screwed on and off, as shown in Figure 5. In otherdesigns tubes may have a collar or recessed ring around them that engages in acorresponding (opposite) feature on the rack which gives a positive positional stopwhich holds the tube in place. It is important to note that none of these features areessential for the operation of the present invention and are mentioned only by way ofbackground information.

The microplate rack 12 has a skirt 13 and the lower edge 15 of the skirt 13 has anoutwardly directed rim 16 enabling the plate racks to be stacked one on top of eachother. The individual tubes 11 are mounted in openings in the rack 12 with the rims 17of the tubes extending above the surface of the body of the rack 12.

It will be appreciated that the design of multiwell plates is subject to a number ofstandards, such as the SBS Standard, in order to ensure compatibility betweenmicroplates from different manufacturers. But a number of variations are commonlyencountered. For example, a microplate typically contains 6, 24, 96, 384 or even 1536sample wells in a fixed array. The wells are usually substantially circular in cross-section but for compound storage applications square wells with close fitting lids orcaps may be preferred.

The wells may be integral with the plate or individual, separate, or stand alone items,as those shown in Figure 1. There is an advantage to using separate wells, rather thanwells integral with the plate, because separate wells can be picked up, usuallyrobotically, and re-organised into a new order in a different microplate. This isparticularly important in sample or compound library applications.

In these applications the individual tubes or wells are inevitably capped and a 96 wellarray of capped tubes is shown in Figure 2 where the same numbering system as thatused in Figure 1 has been employed.

Figure 2 shows individual caps 18, typically made from silicone rubber, thermoplasticelastomers such as Santoprene (RTM) or Evoprene (RTM), or other soft deformableplastics material, inserted into each well. Such caps are either inserted into the wellsmanually or by robotic handling machines. A wide variety of these caps arecommercially available as both individual caps and strips of caps. The presentinvention works well with both cap formats.

Having arranged the required capped wells into a microplate rack, in a first step of themethod the microplate array is placed into a plate sealer, which is in effect a type offilm application device. A wide variety of both manual and automatic plate sealers arealready commercially available such as those supplied by Thermo-Fisher, AgilentTechnologies and 4titude Limited. These plate sealers are presently used to seal afilm, usually a heat sealable film or an adhesive backed film, onto the exposed rims ofthe wells 17 and this provides an alternative method of sealing wells to the use of caps18 as shown in Figure 2. We have unexpectedly found that the same types of film willalso bond or weld effectively to the upper outside exposed surface of the caps 18 in asecond step of the method. A variety of sealing films are already commercially available, such as those suppliedby 4titude Limited, The North Barn, Surrey Hill Business Park, Damphurst Lane,Wotton, Surrey RH5 6QT, United Kingdom. These are supplied in both adhesive sealand heat seal formats and in both sheet and roll form. Where a roll or web of film isused this is preferably pre-perforated for easy division into strips or sheets during theheat sealing process or cut by the machine. A strong film such as a Polyester film ispreferred and one which incorporates a foil layer gives suitable strength. A metal ormetallic foil layer such as aluminium foil laminated to the sealing layer is particularlysuitable.

In order to perform a third step of the method a strong bond between the film and thetop of each cap is important. A type of film which gives a substantially permanent weld between the film and the top of the cap is preferred. By using a heat seaiabie film thatis compatible with the material from which the caps are made, and the appropriatetime and temperature for the heat sealing operation, the heat seaiabie film can bemade to form a substantiaily permanent weld seai to the exposed tops ofthe tube capsin the tube array. An example of this type of material compatibility is where the capsare made from a material containing polypropylene and the heat seaiabie film includesa polypropylene containing layer on the side of the film that is placed against the topof the caps. Many thermoplastics or thermosoftening plastics can be used to form asubstantially permanent weld seal of this type in this application, depending on thecomposition of the caps. A wide variety of heat sealable films and foils are alreadycommercially available and well known to those skilled in the heat sealing process.

An example of a suitable film that gives a substantially permanent weld in this type ofmethod is Thermal Bond (4ti-0590) which is a laminate material where the sealinglayer comprises a 20 micron polypropylene layer laminated to a 60 micron aluminiumlayer.

As described above it is also possible to use a heat or pressure activated adhesivewhere an adhesive layer on the film is activated by heat or by pressure to make it bondstrongly to the top of the caps.

An example of the result of performing this step of the method is shown in Figure 3,where a sheet of film 20 has been bonded to the top of the caps 18 across the wholeof the tube array.

In the third step in the method an upward force is applied to the film sheet whilstholding down the microplate. As a result the film is peeled or pulled back away fromthe mlcropiate and the wells. The film, complete with the tube caps securely bondedor welded to it, is thus separated from the de-capped wells and can ultimately bediscarded. This operation is shown in progress in Figure 4. Friction between the sideof the wells and the sides of the holes in which they sit in the mounting plate helpsretain the wells in their original array format.

The caps and film strip combination are generally not re-used and can be disposed of.However, it would be possible to manually replace the same 96 caps onto the same96 wells if that was considered desirable.

The peeling away or pulling operation in step (iii) described above and shown in Figure4 was carried out manually, but robotic handling is preferred in many applications. Toassist with robotic handling holes or apertures are incorporated in one or more edgesof the strip (not shown). A robotic hook or finger can be inserted into one or more ofthese holes in order to apply the necessary upwards force to carry out the peelingprocess. These hole(s) can be located along the short edge of the film or along thelong edge, or even along opposing edges.

Bearing in mind the peeling action required to remove the film strip/caps combination,it is particularly advantageous if at least one robotic handling means is located on acorner of the film strip. This facilitates peeling the cap/strip combination from onecomer, as shown in Figure 4, and in a direction or axis substantially diagonally acrossthe microplate array.

This method lends itself to automation and there is described herein an apparatus ordevice for carrying out such a process. A microplate or tray containing capped tubesis placed on a platform or conveyor belt and transported on this transport system toan adhesive film application station at which an adhesive film is applied over the topof the array of caps. The adhesive film has an adhesive surface which has a widthsubstantially the same or greater than the width of the tube array, and a lengthsubstantially the same or greater than the length of the tube array.

Where the adhesive film is heat activated it may be necessary to allow the film to coolbefore carrying out the de-capping operation.

The microplate or tray is then held down to resist an upward force applied to the film.This holding down operation can be carried out in a number of ways depending on thedesign of the microplates or trays being used. For example, if the microplate/tray hasa skirt, and the lower edge of the skirt has an outwardly directed rim, as shown as 16in the Figures, then the microplate/tray can be held down by means of this rim.

Alternatively, such microplates/trays often have indentations or depressions around ornear their edges such as indentations 21, 22, and 23 shown in Figure 1. Theseindentations, as well as the top upper edge surface of the microplate/tray providefeatures through which a downward force or pressure can be applied to resist theupward force being applied to peel or pull back the film/cap combination away fromthe microplate and the wells.

In the present description the terms “downward" and "upward" relate to thosedirections as applied to a microplate/tray in the configuration as shown in Figures 1 to 4. So a downward force would press the microplate/tray into the plane that it is restingon and an upward force would tend to move the caps up and away from the tubeopenings.

The cap removal process may take place at a decapping station, away from theadhesive film application station. The film and caps can be collected on a collectionroller or take-up reel and discarded at an appropriate time. It will be appreciated thatthe web of film with the caps adhered to it will be very much thicker than the film priorto use, and therefore take up a much greater volume on a reel. As an alternative thefilm and cap combination may not be reeled up but simply collected in a wastereceptacle.

Where individual sheets of adhesive film are used to bond to the tube caps thesesheets can be provided as an input feed to the de-capping apparatus or can be formedduring the process from a continuous roll or web of adhesive film.

The motion of a microplate/tube rack through the various stages and operations in theapparatus may be controlled by one or more microprocessor controllers, or may becontrolled manually by an operator.

Claims (1)

1. CLAIMS An adhesive film suitable for use in a method for de-capping capped tubes inan array, said adhesive film incorporating one or more apertures in the adhesivefilm enabling a robot machine to engage with the adhesive film once sealed tothe tube caps in order to peel away the tube caps from the tubes in the array. An adhesive film according to Claim 1 wherein the aperture(s) are locatedsubstantially at or towards an end of the adhesive film. An adhesive film according to Ciaim 1 wherein the aperture(s) are locatedsubstantially at or towards a side of the adhesive film.