EP0836884A2 - Système d'exécution de procédures de réactions thermiques sans contamination - Google Patents

Système d'exécution de procédures de réactions thermiques sans contamination Download PDF

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Publication number
EP0836884A2
EP0836884A2 EP97118138A EP97118138A EP0836884A2 EP 0836884 A2 EP0836884 A2 EP 0836884A2 EP 97118138 A EP97118138 A EP 97118138A EP 97118138 A EP97118138 A EP 97118138A EP 0836884 A2 EP0836884 A2 EP 0836884A2
Authority
EP
European Patent Office
Prior art keywords
vessel
closure
liquid
vessels
tight
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.)
Withdrawn
Application number
EP97118138A
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German (de)
English (en)
Other versions
EP0836884A3 (fr
Inventor
Gerhard Dr. Bienhaus
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Roche Diagnostics GmbH
Original Assignee
Roche Diagnostics GmbH
Boehringer Mannheim GmbH
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 Roche Diagnostics GmbH, Boehringer Mannheim GmbH filed Critical Roche Diagnostics GmbH
Publication of EP0836884A2 publication Critical patent/EP0836884A2/fr
Publication of EP0836884A3 publication Critical patent/EP0836884A3/fr
Withdrawn legal-status Critical Current

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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
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • 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
    • 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
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids

Definitions

  • the invention relates to a system for the contamination-free processing of thermal Reaction processes and a method for carrying out liquid transport processes into and out of vessels.
  • the method according to the invention can be used in analytical methods which can be falsified by the entry or removal of interfering substances.
  • sample preparation sample preparation
  • amplification e.g. PCR according to EP-B-0 201 184
  • the reaction problem requires closed reaction vessels. At a However, these vessels need to be performed automatically several times be opened and closed. Furthermore, temperatures of 4 - 95 ° C applied, the increased requirements for the security of the vessels put.
  • WO 95/11083 describes a reaction vessel with a closed one, especially for PCR Described septum, which is, however, only for the automatic removal from a reaction vessel, but not suitable for automatic loading.
  • the container with the sample must be opened completely manually.
  • this embodiment is only conditional for the use of disposable pipette tips can be used because a considerable force is required to pierce the septum the usual plastic pipette tips cannot apply.
  • leaves desired lid counter heating due to the thermal instability of the septum only apply conditionally. Both effects run in parallel, i. H. the thinner the septum, the lighter penetrable, the higher the thermolability.
  • EP-A-0 642 828 describes a system with the same components, which are the same Disadvantages.
  • WO 83/01912 describes a vessel for the determination of hemoglobin with the aid of potassium cyanide described, which has a first plug with a channel and a lid Prevents the escape of dissolved potassium cyanide. This vessel is for implementation not thought of and suitable for temperature treatments.
  • WO 94/05425 describes a lid for a container which contains a valve which can be opened by pressing on the lid so that liquid that is in the Lid is in the container can flow.
  • US-A-4,362,698 describes a closure for sample vessels, which consists of two sub-elements exists, which, however, neither close pressure-tight, nor without their destruction Function can be separated from the sample vessel and from each other.
  • DE-A-44 12 286 describes a system with a lid, reaction vessel and lid handler, which enables such a process to be fully automated.
  • it has the disadvantage that an additional device component as a lid handler is needed.
  • This also applies to the embodiment described in DE 29505707. Farther these embodiments are through the separate lid opening mechanism slowly.
  • US-5,282,543 describes a capping of reaction tubes, with the miss are arranged as a single sealing element in a composite. This arrangement is for direct, automatic pipetting into the reaction vessels is unsuitable.
  • the object of the present invention was to provide a system in which the Liquid transport can be carried out using conventional plastic pipette tips can, and which nevertheless enables such a tight closure of the vessels that of the Liquid inside the vessels does not spill out during heating can.
  • the invention relates to a system for processing thermal reaction processes in liquids containing a variety of vessels, a variety of first Closures for individual of these vessels and one or more second closures can seal a large number of vessels at the same time. Also subject of the Invention is a method of transporting a liquid into or out of a vessel Vessel, which is closed with a first and a second sealing element, into or out with the help of a pipetting unit.
  • a reaction vessel in the sense of the invention means a vessel (1) in which a liquid can be stored. It can therefore be closed or locked. However, the vessel has at least one opening, which is connected to the first and second closure can be closed. In addition, the vessel preferably has no opening that cannot be closed or closed in a liquid-tight and pressure-tight manner.
  • the vessel is preferably thermostable, particularly with regard to shape and Inertness towards the liquid to be stored, especially at temperatures up to at 110 ° C.
  • Preferred materials for reaction vessels are preferably thermoformable Plastics such as polystyrene, polyethylene or polypropylene. You can use the Injection molding technology can be manufactured in a simple manner. They are especially for single use.
  • a particularly suitable material for vessels is polypropylene, as it tolerates temperatures up to 110 ° C without deformation.
  • the reaction vessel preferably has a particularly thin wall thickness, preferably between 0.15 and 0.45 mm, particularly preferably approx. 0.3 mm, and preferably has a conical shape that follows is tapered at the bottom.
  • the vessels preferably have a volume of between 0.05 and 50 ml, preferably 0.2 to 2 ml.
  • the external shape of the vessel is usually determined by the The fact that it is a temperature control unit, e.g. B. a Kitzeblock, in the form as good as possible is adjusted. This improves the heat transfer from the temperature control unit through the Wall of the vessel into the interior of the vessel and, if applicable, the one located therein Liquid.
  • Such reaction vessels are commercially available.
  • reaction vessels can also be connected to one another. So it was, for example proved to be expedient, 16 vessels with curved webs in two rows of 8 positions are connected.
  • the vessels are preferably connected to one another in such a way that they are incorporated into conventional thermal cyclers, e.g. B. for implementation a PCR, fit.
  • Several of these joined vessels can be juxtaposed are treated, e.g. B. in 96-well microtitration plate format. If in the following is spoken of a large number of vessels, it is preferably 4 to 96, particularly preferably 8 to 16 vessels.
  • An internal closure (sealing element 2) for this vessel has the function of being unwanted Prevent liquids from escaping from the opening of the vessel.
  • the is preferred inner closure made of an elastic sealing material, e.g. B. latex or silicone rubber.
  • the hardness of the material is preferably 20 to 100 shore, preferably 30 to 60 shore.
  • Elastosil LR 3003/40 (Wacker Chemie GmbH, FRG) used, which has an elasticity of 40 shore.
  • the inner closure has a thickness of 0.1 to 20 mm, particularly preferably 0.5 to 1.2 mm. This is to be understood that this thickness refers to the thinnest point on the outside. So z. B. for Total stiffening of the closure or to adapt the sealing element to the opening of the vessel (e.g.
  • a pipetting unit e.g. B. a plastic pipette tip is inside Closure provided a further dilution or an opening (4).
  • This opening can have different geometric shapes (see FIGS. 7a-7d). So z. B. a Slit with a length of 1 to 15 mm, preferably 1 to 10 mm, can be provided. It is also possible to provide the opening as a cross slot or in a star shape. It's important, that the opening is closed so that no liquid can escape to the outside by itself. Such slots can for example be cut or cut with knives in the first closure to be punched. If desired, you can also use it during the casting process Recesses are kept clear.
  • the inner stopper is a stopper that is separate for each container can be put on (single lock). However, a multiple lock is appropriate the number of reaction vessels possible. Fixing the multiple lock (2) is preferably carried out via a fitting element on the reaction vessel and / or the closure but via sealing rings (15) of the closure, which protrudes into the opening of the vessel (1).
  • the inner closure preferably remains on the vessel and closes the vessel during the entire treatment process and is preferably not removed afterwards.
  • the inner closure preferably covers the entire opening and is particularly preferred also the upper edges of the vessel, but can also be partially inserted into the vessel be.
  • the inner closure is preferably not pressure-tight.
  • An outer closure (sealing element 3) is intended to serve this purpose, whether intentionally or not to seal any leaks in the inner seal from the outside. He therefore covers in all cases all openings in the inner closure, for example as Slit were already preformed or were created (using the pipette tip).
  • This External closure can in principle consist of any materials if they are only firm Allow enough to be pressed onto the vessel opening and / or the inner closure. Prefers are therefore again elastic materials for the outer closure, as described above for the first closure were described. Because the outer closure is not for provision or the opening must be suitable, preferably not from the pipetting unit must be penetrated, larger limits are possible with regard to the thickness, especially upwards.
  • the lid heater which the evaporation may change inner closure to precipitate condensation, can in the outer Closure should be integrated. However, the lid heater can also be used in an independent Component be housed. It is particularly preferred that the outer closure as a thin, removable layer of elastic sealing material, e.g. B. a mat on one heated component is provided, which in its entirety on the Reaction vessel is pressed with the first closure.
  • the outer closure is preferably suitable for the closure of a large number of vessels simultaneously, e.g. B.
  • a feature of a particularly preferred outer closure is that it can be completely separated from the inner closure. This happens when a liquid with the help of a pipetting unit through the inner closure into the vessel to be transported in or out of the vessel. For this process the Removed the outer stopper from the vessel and the inner stopper so that the pipetting needle when passing through the opening of the inner closure, not through the outer closure must pass through.
  • Liquid-tight in the sense of the invention means in particular that liquids are not without the action of additional forces, such as pressure (e.g. by heating) or conscious generation or widen an opening.
  • Pressure-tight means that the closure pressures up to 2.5 bar, preferably up to 1.2 bar, endures without gas or liquid from enclosed space z. B. the vessel allow.
  • the invention also relates to a method for transporting a liquid With the help of a pipetting unit into or out of a vessel, which is connected to a first and second closure is closed, comprising the steps of removing an outer Sealing element (3) from the vessel and an inner sealing element (2), introduction of Pipette into the vessel through the inner sealing element (2) and absorb the liquid into the pipettes from the vessel or dispensing the liquid from the pipetting unit the container.
  • Liquids that can be transported are, for example, sample liquids or derived liquids in which the presence of ingredients is proven should be, e.g. B. serum, buffy coat, plasma and liquids derived therefrom, liquids, are the result of a nucleic acid amplification process, but also liquids, the reagents for the detection, preparation or amplification of ingredients of sample liquids.
  • a pipetting unit is understood to mean a device or a device into which Liquid can be absorbed and released again. This is preferred by sucking in and expelling the liquid into a receiving area of the pipetting unit. In principle, this can also be done with reusable receiving units, such as metal needles, be.
  • plastic pipette tips is particularly preferred (5), which are used only once for liquid transport. This are usually made of materials such. B. polypropylene, which is a mechanical load only endure very limited. Furthermore, they are not very pointed, so that an independent Puncturing conventional lids with them is not possible. For this reason in the sense of the invention it prefers to whom the inner closure is pre-punched Opening, e.g. B. in the form of a slot.
  • the insertion of the pipetting unit into the vessel through the inner closure is preferred made automatically, e.g. B. with the help of a commercially available pipetting machine.
  • a commercially available pipetting machine e.g. B.
  • the manual processing of the introduction of the pipetting unit possible, e.g. B. with a pipette.
  • Reagents for performing a reaction in the vessel to a sample liquid to admit.
  • a sample liquid that has already been processed withdraw certain amount and add it to the pipetting unit.
  • the system according to the invention has particular advantages in processes in which a liquid to be heated in the vessel.
  • the vessel is preferred during heating steps closed by both the inner and the outer closure, so that practical neither liquid nor gas can escape from the vessel.
  • the outer Closure with a certain force depending on the number of reaction vessels held down. This force is 0.1 to 10 N per reaction vessel, preferably 1 to 5 N.
  • This pressure is preferred by vertically pressing the closure, e.g. B. with a Bracket (12), such as a metal plate, which can also contain the lid heater, generated.
  • a Bracket (12) such as a metal plate, which can also contain the lid heater, generated.
  • it is preferred to hold the bracket as uniformly and vertically as possible in the direction of To move the vascular occlusion.
  • the simultaneous closure of all vessels under the same pressure conditions is preferred.
  • the outer closure prevents gaseous liquid components from escaping (e.g. water vapor or aerosols) into the environment outside the Vessel, against the gas pressure.
  • gaseous liquid components e.g. water vapor or aerosols
  • the amplification methods are for example heated and cooled several times of nucleic acids, e.g. B. the polymerase chain reaction. But also simple denaturations and hybridization reactions can include heating steps.
  • a sample liquid pipetted through the inner closure into the vessel, which then serves as a reaction vessel.
  • those required to carry out the desired reaction (s) Reagents either presented or pipetted into the sample liquid.
  • the outer closure is open, i.e. H. the sealing element (3) removed.
  • the outer closure Before carrying out heating or / and cooling steps, the outer closure closed.
  • the outer closure After completion of the temperature steps and preferred after re-setting a gas pressure in the vessel that corresponds to the external pressure the outer closure can be removed. If desired or necessary, will be further pipetting and / or temperature steps carried out, analogously to that described above Action. Should z. B.
  • the process according to the invention preferably contains in a further step after completion each liquid transport through the inner closure the reclosure of the Vessel with the outer closure. After that, further temperature treatment reactions can be carried out be performed.
  • FIG. 1 is the preferred method according to the invention for the transport of liquids shown schematically.
  • a vessel (1) is closed with the help of an inner closure (2), an opening (4), for. B. in the form of a slot.
  • the outer closure (3) is separated from the inner closure. After introducing the Pipetting unit can absorb liquid into it or dispense it out of it will.
  • the outer closure is also open for this. After removing the pipette tip, it will The vessel is closed with the help of the outer sealing element (3) and is used for temperature treatment to disposal.
  • Fig. 2 shows a reaction vessel, as it can be used in Fig. 1, in an enlarged view.
  • a sealing ring (15) can also be seen, the Is part of the inner closure (2).
  • Fig. 3 shows an enlarged view of the state when a pipette tip (5) through the inner Closure (2) is inserted into the vessel (1).
  • the cover (3) is removed.
  • the system according to the invention can preferably be arranged in an arrangement of several Insert the connected reaction vessels (1) (Fig. 4), with the sealing element (3) then serves as a "mat" for a number of reaction vessels.
  • the sealing elements (2) with individual openings (4) can also form a connected unit. Orders in 96-well microtitration plate format are preferred.
  • the sealing element (3) is preferred, as shown in Fig. 4, as an easily replaceable element the cover counter heating block (7).
  • brackets (8) for the Mat provided.
  • the heating element (7) with the mat can be hinged (Pivot point 9) can be folded onto the vessels (1).
  • FIG. 5 shows a variant of the embodiment.
  • a holder (12) for the reaction vessels shaped so that the sealing element (3) simultaneously via a hinge (11) and a frame (10) is integrated and can be opened accordingly, so that a Pipetting, as shown in Fig. 1, can be done.
  • Fig. 6 shows the arrangement of the variant of Fig. 5 in a heating block (6) with a cover counter heating block (7) and pivot point (9).
  • Fig. 7 shows some geometric variants of the opening (4) for insertion according to the invention a pipette tip.
  • 7a and 7b are slits, 7c and 7d are also small Recesses included in the material.
  • the sealing elements are preferably made of silicone, the reaction vessel made of polypropylene.
  • FIG. 8 shows a possibility by forming widenings (14) of the band of the reaction vessels ("Ears") with corresponding holes (13) the silicone seal (2 / not shown) rivet.
  • the sealing ring (15 / not shown) is also used, the protrudes into the reaction vessel (see Fig. 2).
  • reaction vessels 9 and 10 show reaction vessels for carrying out a PCR. It is a matter of 16 reaction vessels connected by curved bars in 2 rows with 8 positions each are. The webs are shaped so that a higher temperature load does not Deformation results. The reaction vessels have widenings (ears) (14, see Fig. 8) for welding to the sealing element (2) (see Fig. 11).
  • a mat is shown as a sealing element (2). It contains the individual Vessels associated positions slots (4).
  • the sealing element can be widened (13) welded onto the vessel plate (top).
  • a sealing element (2) is shown in section. You can see them in the vessels protruding sealing rings (15) and the slots (4) (in longitudinal section).
  • FIG. 13 shows a multiple device according to FIG. 5 in the opened state. It is possible, e.g. B. using a barcode to attach an identification of the device on the flap.
  • Microtitration plate formats are possible and inexpensive to manufacture.
  • at least one of the closures is self-closing.
  • a huge advantage of the system according to the invention is that a low-contamination multiple removal of Liquid from the vessel itself is possible after PCR.
  • polypropylene Novolen 1100 UCX with an additive 11 NU 10 in a concentration of 3.5%) used as material for the reaction vessels.
  • the reaction vessels have a volume of 0.25 ml.
  • the sealing element (2) preferably consists of elastic silicone rubber with a thickness of 1 mm, Elastosil LR 3003/40 (Wacker Chemie GmbH), which has an elasticity of 40 shore (DIN 53505).
  • the sealing element (3) consists of the same material, also with a thickness of 1 mm.
  • An analog reaction vessel with a higher volume e.g. B. 1.5 ml and the invention System can also be used for sample preparation in nucleic acid analysis will.
  • B. Vogelstein and D. Gillespie Proceedings of Natl. Acad. Sci. USA, February 1979, vol. 76, no. 2, pp 615 -619) are for the isolation of Nucleic acid from agarose gels according to Method II, various tempering steps at 25 ° C and 37 ° C necessary.
  • the invention can be used to reduce the risk of contamination Use system preferably for automation of the protocol.
  • R. Boom et al. J. of Clinical Microbiology, March 1990, pp. 495-503
  • P.M P.M.
EP97118138A 1996-10-21 1997-10-18 Système d'exécution de procédures de réactions thermiques sans contamination Withdrawn EP0836884A3 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19643320 1996-10-21
DE1996143320 DE19643320A1 (de) 1996-10-21 1996-10-21 System zur kontaminationsfreien Bearbeitung von thermischen Reaktionsprozessen

Publications (2)

Publication Number Publication Date
EP0836884A2 true EP0836884A2 (fr) 1998-04-22
EP0836884A3 EP0836884A3 (fr) 1999-01-13

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Family Applications (1)

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EP97118138A Withdrawn EP0836884A3 (fr) 1996-10-21 1997-10-18 Système d'exécution de procédures de réactions thermiques sans contamination

Country Status (3)

Country Link
EP (1) EP0836884A3 (fr)
JP (1) JPH10132713A (fr)
DE (1) DE19643320A1 (fr)

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NL1012996C2 (nl) * 1999-09-08 2001-03-12 Micronic B V Afsluitmat voor het afsluiten van reageerbuizen.
WO2002026384A2 (fr) * 2000-09-29 2002-04-04 Promega Corporation Plaque d'essai a plusieurs cupules et porte-plaque, et procede de montage de la plaque
US6875604B2 (en) 2000-02-02 2005-04-05 Applera Corporation Thermal cycling device with mechanism for ejecting sample well trays
WO2005097323A1 (fr) * 2004-04-07 2005-10-20 Agilent Technologies, Inc. Couvercle muni d'une ouverture reutilisable
EP1638688A1 (fr) * 2003-05-13 2006-03-29 Valinsky, amos Indicateur pour plaque multipuits et son procede d'utilisation
WO2007029101A2 (fr) * 2005-09-06 2007-03-15 Bioinnovations Oy Recipient et procede de fabrication du recipient
USRE39566E1 (en) 1999-09-29 2007-04-17 Applera Corporation Thermocycler and lifting element
US7550291B2 (en) * 2003-03-05 2009-06-23 Roche Molecular Systems, Inc. Vessel system for the treatment and/or storage of liquids
US8211710B2 (en) * 1999-05-14 2012-07-03 Dickey Kathleen A Method for accessing the contents of a closed collection device
ITRM20110226A1 (it) * 2011-05-03 2012-11-04 Mauro Pepe Kit per l'analisi delle urine.
US8323588B2 (en) 2007-05-04 2012-12-04 Quantifoil Instruments Gmbh Sample handling device for and methods of handling a sample
EP2752671A3 (fr) * 2010-07-23 2016-08-24 Beckman Coulter, Inc. Système ou procédé comprenant des unités analytiques
US9829416B2 (en) 2012-02-24 2017-11-28 Roche Molecular Systems, Inc. Closure with septum strip
EP3379255A4 (fr) * 2015-11-16 2018-09-26 Konica Minolta, Inc. Procédé de détection, dispositif de détection, et kit d'inspection
WO2021231938A1 (fr) * 2020-05-15 2021-11-18 Meso Scale Technologies, Llc. Couvercles amovibles compatibles avec l'automatisation et procédés d'utilisation

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JP3476373B2 (ja) * 1998-09-24 2003-12-10 東芝セラミックス株式会社 珪素質分析試料中の不純物高感度分析のための試料処理器及びそれを用いた分析方法
JP3390377B2 (ja) * 1999-10-05 2003-03-24 株式会社日立製作所 反応装置
JP2002228669A (ja) * 2001-01-31 2002-08-14 Shimadzu Corp 液体移送器及び反応容器
WO2005092734A1 (fr) 2004-03-26 2005-10-06 Chugai Seiyaku Kabushiki Kaisha Feuille ayant des caractéristiques élastiques et des caractéristiques de glissement, et conteneur pour remplir /verser le solvant, utilisant cette feuille
JP4870991B2 (ja) * 2006-01-20 2012-02-08 凸版印刷株式会社 反応容器
JP5372899B2 (ja) * 2010-12-14 2013-12-18 サクラファインテックジャパン株式会社 包埋皿およびその製造方法
US11333674B2 (en) 2015-11-16 2022-05-17 Otsuka Pharmaceutical Co., Ltd. Test kit, liquid delivery method and testing apparatus using test kit
WO2023026361A1 (fr) * 2021-08-24 2023-03-02 株式会社日立ハイテク Cloisons

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WO1983001912A1 (fr) * 1981-11-30 1983-06-09 Suovaniemi, Osmo Dispositif de securite permettant de sceller un tube de test
DE9006079U1 (fr) * 1990-05-30 1990-09-13 Bethkenhagen, Juergen, 5223 Nuembrecht, De
WO1992020449A1 (fr) * 1991-05-20 1992-11-26 Closure Technologies, Inc. Bouchon d'etancheite a clapet unidirectionnel
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Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8211710B2 (en) * 1999-05-14 2012-07-03 Dickey Kathleen A Method for accessing the contents of a closed collection device
WO2001017682A1 (fr) * 1999-09-08 2001-03-15 Micronic B.V. Mat d'etancheite pour la fermeture de tubes d'essai de reactions
NL1012996C2 (nl) * 1999-09-08 2001-03-12 Micronic B V Afsluitmat voor het afsluiten van reageerbuizen.
USRE39566E1 (en) 1999-09-29 2007-04-17 Applera Corporation Thermocycler and lifting element
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DE19643320A1 (de) 1998-04-23
JPH10132713A (ja) 1998-05-22
EP0836884A3 (fr) 1999-01-13

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