EP1142795A2 - Couvercle en forme de nappe flexible - Google Patents

Couvercle en forme de nappe flexible Download PDF

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Publication number
EP1142795A2
EP1142795A2 EP01106616A EP01106616A EP1142795A2 EP 1142795 A2 EP1142795 A2 EP 1142795A2 EP 01106616 A EP01106616 A EP 01106616A EP 01106616 A EP01106616 A EP 01106616A EP 1142795 A2 EP1142795 A2 EP 1142795A2
Authority
EP
European Patent Office
Prior art keywords
cover
layer
mat
plate
covering
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.)
Granted
Application number
EP01106616A
Other languages
German (de)
English (en)
Other versions
EP1142795B8 (fr
EP1142795B1 (fr
EP1142795A3 (fr
Inventor
Wolfgang Dr. Heimberg
Markus Schürf
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.)
F Hoffmann La Roche AG
Original Assignee
MWG Biotech AG
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 MWG Biotech AG filed Critical MWG Biotech AG
Publication of EP1142795A2 publication Critical patent/EP1142795A2/fr
Publication of EP1142795A3 publication Critical patent/EP1142795A3/fr
Application granted granted Critical
Publication of EP1142795B1 publication Critical patent/EP1142795B1/fr
Publication of EP1142795B8 publication Critical patent/EP1142795B8/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples

Definitions

  • the invention relates to a cover mat for covering several in a plate Body of trained, upwardly open reaction vessels that are ready to run chemical and / or microbiological reactions, e.g. the PCR method, are provided.
  • This patent application relates to a thermal cycler device for implementation chemical and biological reactions in which a plate-shaped body is absorbed can be, which has upwardly open reaction vessels.
  • This Thermal cycler device has a lid and a closing mechanism for Fix the lid.
  • An electrically controllable actuator is provided that put pressure on the reaction vessels after fixing the lid can.
  • a rubber mat is proposed for sealing the reaction vessels to be arranged between the reaction vessel which is open at the top and the lid, so that the reaction tubes through the rubber mat that from the lid against the Reaction vessels are pressed, are sealed.
  • reaction vessels are covered with an oil or wax layer sealed.
  • This layer of oil or wax is placed on top of the reaction vessels Chemical mixture applied and should ensure that between the neighboring reaction vessels no transfer of chemical partial quantities is possible.
  • chemical or biological reactions that have no significant Temperature increase take place, is the application of such an oil or Wax layer useful.
  • high reaction temperatures occur or the chemical mixtures are heated, e.g. the case with the PCR method the oil or wax layer becomes thin and does not provide a suitable one Protection against contamination by chemicals from a neighboring reaction vessel Especially when the chemical mixture boils, the oil or Wax layer no effective protection against contamination.
  • reaction vessels are therefore covered with a thin plastic film welded so that each individual reaction vessel is closed.
  • the reaction vessels are usually formed in standardized microtiter plates.
  • the foil is welded onto the microtiter plates in such a way that around each reaction vessel an annular weld is formed.
  • US 5,604,130 describes a cover for microtiter plates.
  • This cover is a rigid, flat element or a flexible polymer film.
  • This polymer film can be made from different flexible polymer materials, e.g. Rubber, Silicone rubber, polyurethane rubber and the like may be formed.
  • the thickness of this Foil is specified with 0.9 mm to 1.5 mm.
  • the flexible polymer film cannot can be handled with an automatic device since the gripping a flexible film is very difficult.
  • the flat, rigid element is fundamental suitable to be detected by an automatically operating device. in practice, however, it turns out that such covers after the implementation of reactions that cause a negative pressure in the individual reaction vessels, are difficult to detach from the reaction vessels and the corresponding Accordingly, the device must be dimensioned large.
  • a cover for microtiter plates is described in WO 99/61152.
  • a multi-layer film is shown here, which has a back layer and a sealing layer includes.
  • the supine position is stiff. However, it can also be made of a flexible material be trained.
  • the sealing layer is made of an inelastically deformable material such as. Silicone, designed to provide an airtight seal. This sealing layer has an adhesive surface so that the cover on the microtiter plate is liable.
  • the invention has for its object to provide a cover mat with the a plate-shaped body, which is open at the top and is safe can be sealed easily in an automated process and can be used repeatedly, with no great forces to lift off the Covering mat are required.
  • the invention is characterized by a cover mat with the features of claim 1 solved.
  • Advantageous refinements are specified in the subclaims.
  • the cover mat according to the invention is for covering several in one plate-shaped Body of trained, upwardly open reaction vessels, provided that to carry out chemical and / or microbiological reactions, e.g. the PCR method can be used.
  • the cover mat is made of an elastic material formed, the cover mat has a soft lower layer, which for Stiffening is provided with a carrier plate, and the carrier plate is curved in this way is that they have a flat surface on the entire surface of the carrier plate Pressure body of at least 5 N applied elastically hugs the flat pressure body and a correspondingly bend-free one Takes shape.
  • This curvature of the support plate causes the cover mat to move after the Carrying out the chemical and / or microbiological reactions of which the Plate-like body having reaction vessels lifts off in regions as soon as a pressure with which the cover plate during the chemical and / or microbiological reaction is pressed against the plate-shaped body, canceled becomes.
  • the carrier plate is made of such a rigid material that the cover mat even in reactions in which there is negative pressure in the individual reaction vessels arises, in certain areas from the plate-shaped body. Hereby ensures that no high forces are required to lift off the cover mat of the plate-shaped body are necessary, even if in the individual reaction vessels a negative pressure is generated.
  • the carrier plate returns to its original curvature, the cover mat already detached from a large part of the reaction vessels and only by a few Reaction vessels, which are arranged in areas on which the curved cover mat is held by the negative pressure therein.
  • the resulting holding force is so low, however, that it can be lifted by a Handling device is safely lifted from the plate-shaped body.
  • FIG. 1 shows an embodiment of the cover mat according to the invention in one perspective view looking at the underside of the cover mat 1.
  • FIG. 2 shows a section through the cover mat from FIG. 1 along the line A - A.
  • cover layer 2 which consists of a pore and groove-free smooth plastic material is formed.
  • cover layer 2 which consists of a pore and groove-free smooth plastic material is formed.
  • silicone due to its smooth surface texture is very suitable material for the cover layer.
  • the one shown in Figs. 1 and 2 Embodiment has a cover layer made of silicone with a thickness of approx. 1 mm.
  • the cover layer 2 is connected to a compensation layer 3 arranged above it.
  • the cover layer 2 and the compensation layer 3 thus form a composite material.
  • the compensation layer 3 of the illustrated embodiment has a thickness of 3 mm.
  • the leveling layer is made of a softer material than the cover layer 2.
  • the Shore hardness of the compensation layer 3 should not be greater than 15 ° his.
  • the cover layer can have a Shore hardness of up to 50 °.
  • the Shore hardness of the cover layer 2 is expediently approximately 20 ° to 40 °.
  • the compensating layer is made of a silicone foam educated.
  • it can also be made of another, similarly elastic Plastic foam, such as B. foam rubber, neoprene foam or the like his.
  • the cover layer 2 and the compensation layer 3 are by vulcanization or one so-called cold composite areally connected to each other.
  • the compensating layer 3 preferably consists of a flexible plastic foam material, that allows the cover mat 1 under pressure is significantly compressed.
  • the compensation layer 3 is, for example, by gluing to a carrier plate 4 attached.
  • the carrier plate 4 is formed from a thin aluminum sheet.
  • the cover mat has an approximately rectangular shape in plan view.
  • the length the short side edge of the cover layer 2 and the compensation layer 3 is approximately 7.5 cm and the length of the long side edge about 11.5 cm.
  • the carrier plate 4 stands on the long side edges of the cover layer and the leveling layer 3 Piece before. The carrier plate 4 thus faces the cover layer 2 and the Compensating layer 3 protruding strips 5.
  • On the short side edges of the cover mat 1 are adjacent to the corners angled down, a hook 6 webs formed.
  • the downwardly angled section of the hook 6 is longer than the entire thickness of the covering layer 2 and the compensating layer 3 it is ensured that when the cover mat 1 is placed on a smooth surface Footprint the cover layer 2 does not touch the footprint. This will create a Contamination of the cover layer 2 avoided.
  • the hooks also serve as a guide when placing the cover mat on a pipetting plate. Such hooks can therefore also be provided on the long sides of the cover mat.
  • the carrier plate 4 is curved in such a way that it extends over the entire surface the support plate with a flat pressure body applied load of at least 50 N resiliently hugs the flat pressure body and assumes a correspondingly flat, curvature-free shape.
  • the load to bring about the flat shape of the cover mat. 1 be at least 80 to 100 N.
  • the curvature is Carrier plate 4 designed such that the carrier plate 4 is directed upwards Has curvature, the apex of which is approximately in the central region of the cover mat 1 lies.
  • the edge areas of the cover mat 1 can be compared to the in the central area a little upwards.
  • Thermal cycler device 7 has a housing 8 serving as a base body is cuboid.
  • the upper boundary surface of the housing 8 serves as Recording area 9 for receiving a plate-shaped body 10 on which several upwardly open reaction vessels 11 are formed.
  • the plate-shaped body 10 a pipetting plate 10 or a microtiter plate 10.
  • Such plates are thin-walled plastic parts on which the reaction vessels 11 are formed and arranged in rows and columns.
  • the height of the individual differs accordingly Microtiter plates.
  • the receiving area 9 is in the form of a blind hole open at the top Provide recesses into which the respective reaction vessels 11 of the microtiter plate 10 are used.
  • a heating and / or cooling element such as e.g. a Peltier element be provided for heating and cooling the reaction vessels 11.
  • a cover 12 Above of the receiving area 9, a cover 12 is arranged, which has a hinge joint 13 is pivotally attached to the housing 8.
  • the lid is formed from a lid base body 14 and a lid segment 15.
  • the lid segment 15 preferably forms a heating plate, which on a Temperature can be heated, which is slightly above the maximum reaction temperature lies that of the arranged in the receiving area 9 heating and / or Cooling element is generated.
  • the heating and / or cooling element can be, for example Follow the temperature profile in the range from 0 ° C to 95 ° C, then the cover segment 15 is heated to 100 ° C, for example. This will cause condensation on Cover segment avoided.
  • the lid segment 15 is displaceable in the lid base body 14 along its normal arranged. Between the upper surface of the lid segment 15 and the base body 14, spring elements 16 are arranged, which are the cover segment 15 press against a stop 17 of the cover body 14.
  • the spring elements 16 are, for example, with a total spring force of approximately 20 N. biased.
  • an electrochemical linear motor 19 is arranged in the central area between the lid segment 15 and the lid body 14.
  • electrochemical Linear motors are also known as electrochemical actuators.
  • the electrochemical linear motor By supplying electricity, that is, by charging the electrochemical motor hydrogen is released in the bellows, causing the bellows to stretch and performs a linear movement.
  • the bellows has an electrical resistance discharge, the hydrogen gas is chemically bound, causing the gas volume is reduced and the bellows is contracted.
  • the electrochemical linear motor corresponds to a pneumatic one Element that does not require an external compressed air supply, however can be controlled electrically, there being three control states charging, holding and unloading there.
  • the electrochemical linear motor 19 is attached at one end to the cover segment 15, while its opposite end 20 is free to move.
  • the electrochemical linear motor that is to say when stretched, the electrochemical is based Linear motor 19 on the cover body 14 and thereby pushes it Cover segment 15 downward in the direction of the receiving area 9 of the housing 8.
  • a microtiter plate 10 is inserted in the receiving area 9, in its reaction vessels 11 Mixtures of chemical reagents are included.
  • On the microtiter plate 10 lies the covering mat 1 according to the invention with its covering layer 2 pointing below.
  • the cover segment 15 is the electrochemical linear motor 19 pressed down so strongly that the cover mat 1 has a flat shape assumes.
  • the cover layer 2 is in this case against the edge regions of the open top Reaction vessels 11 pressed so that each individual reaction vessel 11 is securely sealed becomes. This will contaminate the individual reaction mixtures safely avoided by reagents from adjacent reaction vessels 11, even if the reaction mixtures should start to boil.
  • the cover mat 1 has sufficient strength so that it itself when a negative pressure develops in the reaction vessels 11, it is not permanently plastic is deformed, but after loosening the cover mat 1 from the microtiter plate 10 returns to its original shape.
  • the electrochemical linear motor 19 is discharged, so that it contracts and which during the execution of the chemical reactions the cover mat 1 applied pressure is released. Then the lid 12 of the Thermal cycler device 7 opened. Due to the curvature of the cover mat 1 the cover mat 1 lifts from the microtiter plate at its upwardly curved area 10 from. Since the carrier plate 4 is so rigid that at least one Force of 50 N, preferably more than 80 N to 100 N for flat pressure the microtiter plate 10 is necessary, it rises with the appropriate force the microtiter plate. As a result, the cover mat 1 can also be used for sample vessels 11 are released and lifted off, in which a negative pressure has been generated.
  • the Cover mat 1 is thus only on the areas of the microtiter plate 10 the effect of the negative pressure on which it rests. The whole resulting adhesive forces between the cover mat 1 and the microtiter plate 10 are therefore significantly less than if the cover mat 1 with its entire Surface would rest on the microtiter plate 10. It has been shown that even if the chemical reactions create negative pressure, the curved one Cover mat 1 can be lifted off the microtiter plate 10 without this the microtiter plate 10 is also raised. This makes it possible for the invention Cover mat 1 can be handled fully automatically, because at Lifting the cover mat 1 off the microtiter plate 10 there is no risk that the microtiter plate is also lifted.
  • the cover mat according to the invention can thus be used to close microtiter plates in devices for the automatic implementation of chemical or biological Procedures are used. Such a device is shown schematically in FIG. 4 shown.
  • Such a device for the automatic execution of chemical and biological Reactions has a rectangular base plate 22 with two end edges 23 and a front and rear longitudinal edge 24.
  • On the base plate 2 is at the rear Longitudinal edge 24 a rear wall 25 is arranged.
  • At the top of the border is in the back wall 25 a horizontal, to the rear longitudinal edge 24 of the Base plate 22 provided parallel rail 26 on which two robot arms 27th arranged to be movable in the longitudinal direction of the rail 26 (double arrow 28, X direction) are.
  • the robot arms 27 are each rectilinear, rigid arms that are parallel to the front edges 23 of the base plate 22 are arranged. They are therefore perpendicular to the Level of the rear wall 25.
  • the operating arms 30 are each along one in the longitudinal direction (Y direction) of the robot arms 27 Rail (not shown) can be moved. In addition, the operating arms are also in vertical direction (Z direction) can be moved.
  • a pipette tip assembly 31 with eight pipette tips and the other Actuating arm 30 a fork-shaped gripping device 32 is attached. With the gripping device 32, both microtiter plates and cover mats 1 can be added and be transferred.
  • the gripping device has two gripping arms, each with projections projecting inwards, with which the strips 5 of the covering mat 1 can be attacked.
  • the base plate 22 On the base plate 22, four thermal cycler devices 7 are arranged, which with their receiving area 9 and their lids 12 shown in the opened state are.
  • the sample holder 33 and the pipette holder 34 are essentially Identically designed holders on which microtiter plates are placed can be.
  • the microtiter plates placed on the holders 33, 34 are through the brackets 33, 34 aligned exactly with respect to the base plate 22, so that the location of the individual vessels formed on the microtiter plates is exact is fixed and these can be controlled precisely by the robot arms.
  • the pipetting holders 34 define pipetting stations at which the pipetting is carried out the pipette tip arrangement 31 is executed.
  • On the base plate 22 On the base plate 22 are still a shaft 40 with unused cover mats and a shaft 41 for storing the cover mats 1 provided.
  • the device also has a chemical reservoir 42 with several upward open vessels with various chemicals and a stacking device 43 for receiving of several microtiter plates.
  • the stacking device 43 is vertical from the back wall 25 projecting webs 44.
  • a user places on the sample holder 33 a microtiter plate 10, in the sample vessels of which contain sample substances are. These sample substances are either directly on this microtiter plate or on additional microtiter plates on the pipetting holders with others Reagents are added from the chemical reservoir 42 and in one of the thermal cycler devices 7 chemical and / or biological reactions, e.g. the Subjected to PCR procedures.
  • the individual microtiter plates are included in the Gripping device 32 removed from the sample holder 33 or from the pipetting holder 34 and inserted into the thermal cycler device 7.
  • Microtiter plate 10 located in thermal cycler device 7 becomes a cover mat 1 hung up, which is removed from the stack of unused cover mats.
  • the gripping device guides and grips the covering mats 1 32 out.
  • a thermal cycler device 7 are each a microtiter plate and introduced a cover mat 1, so the motorized cover 12 of the respective Thermocycler device 7 automatically closed and the corresponding Procedure can begin.
  • the lid 12 in turn open automatically, the respective cover mat picked up by the gripping device 32 and on the stack 41 of the cover mats used filed.
  • this device can work fully automatically without the individual reaction vessels of Hand, for example by welding with a film, be sealed manually have to.
  • the cover mats 1 used in the stack 41 are merely removed from time to time and the stack 40 with cleaned cover mats 1 Mistake.
  • the curved cover mats described above are preferred used as it detaches itself from the microtiter plates after performing the reactions have it lifted off, even if there is negative pressure in individual test tubes should arise.
  • the cover layer can be made of a different material than Silicone be formed, provided that this material to seal the reaction vessels is sufficiently smooth.
  • the leveling layer does not have to be made of a plastic foam exist if it has the necessary flexibility.
  • the carrier plate can e.g. made of spring steel or another Alsatian and preferably good heat conductor Material be formed.
EP01106616A 2000-04-08 2001-03-15 Couvercle en forme de nappe flexible Expired - Lifetime EP1142795B8 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE20006546U DE20006546U1 (de) 2000-04-08 2000-04-08 Abdeckmatte
DE20006546U 2000-04-08

Publications (4)

Publication Number Publication Date
EP1142795A2 true EP1142795A2 (fr) 2001-10-10
EP1142795A3 EP1142795A3 (fr) 2003-11-19
EP1142795B1 EP1142795B1 (fr) 2005-12-28
EP1142795B8 EP1142795B8 (fr) 2006-03-22

Family

ID=7940031

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01106616A Expired - Lifetime EP1142795B8 (fr) 2000-04-08 2001-03-15 Couvercle en forme de nappe flexible

Country Status (7)

Country Link
US (1) US6518060B2 (fr)
EP (1) EP1142795B8 (fr)
JP (1) JP3843754B2 (fr)
AT (1) ATE314277T1 (fr)
DE (2) DE20006546U1 (fr)
ES (1) ES2254276T3 (fr)
NO (1) NO20011768L (fr)

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DE10205977A1 (de) * 2002-02-08 2003-08-28 Eppendorf Ag Workstation zum Durchführen von chemischen und biologischen Verfahren in Mikrotiterplatten
DE102013114732A1 (de) 2013-12-20 2015-06-25 Hamilton Bonaduz Ag Abdeckvorrichtung, insbesondere Deckel für die Abdeckung von Reaktionsgefäßen
WO2015091928A1 (fr) 2013-12-20 2015-06-25 Hamilton Bonaduz Ag Dispositif de recouvrement, en particulier couvercle servant à couvrir des récipients réactionnels
US10421073B2 (en) 2013-12-20 2019-09-24 Hamilton Bonaduz Ag Covering device, in particular lid, for covering reaction vessels

Also Published As

Publication number Publication date
ES2254276T3 (es) 2006-06-16
DE20006546U1 (de) 2001-08-23
ATE314277T1 (de) 2006-01-15
JP2001352967A (ja) 2001-12-25
EP1142795B8 (fr) 2006-03-22
DE50108502D1 (de) 2006-02-02
US20020028507A1 (en) 2002-03-07
EP1142795B1 (fr) 2005-12-28
EP1142795A3 (fr) 2003-11-19
US6518060B2 (en) 2003-02-11
NO20011768D0 (no) 2001-04-06
NO20011768L (no) 2001-10-09
JP3843754B2 (ja) 2006-11-08

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