WO1991007504A1 - Improved dna polymerisation device - Google Patents

Improved dna polymerisation device Download PDF

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Publication number
WO1991007504A1
WO1991007504A1 PCT/AU1990/000560 AU9000560W WO9107504A1 WO 1991007504 A1 WO1991007504 A1 WO 1991007504A1 AU 9000560 W AU9000560 W AU 9000560W WO 9107504 A1 WO9107504 A1 WO 9107504A1
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WO
WIPO (PCT)
Prior art keywords
heat sink
dna
mass
heating
heat
Prior art date
Application number
PCT/AU1990/000560
Other languages
French (fr)
Inventor
John Michael Corbett
Original Assignee
Kindconi Pty. Ltd.
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 Kindconi Pty. Ltd. filed Critical Kindconi Pty. Ltd.
Publication of WO1991007504A1 publication Critical patent/WO1991007504A1/en

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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
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • G—PHYSICS
    • G05—CONTROLLING; REGULATING
    • G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
    • G05D23/00—Control of temperature
    • G05D23/19—Control of temperature characterised by the use of electric means
    • G05D23/1919—Control of temperature characterised by the use of electric means characterised by the type of controller
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00495—Means for heating or cooling the reaction vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/0059—Sequential processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the present invention relates to a device for use in DNA polymerisation.
  • a DNA segment of up to approximately six thousand base pairs in length may be amplified exponentially starting from as little as a single gene copy by means of polymerised chain reaction.
  • a denatured DNA sample is incubated with two oligonucleotide primers that direct the DNA polymerase-dependent synthesis of complimentary strains.
  • Multiple cycles of synthesis each afford an approximate doubling of the amount of target sequence.
  • Each cycle is controlled by simply varying the temperature to permit denaturation of the DNA strands, annealing of the primers, and synthesis of new DNA strands.
  • the use of a thermostable DNA polymerase obviates the necessity of adding new enzyme for each cycle, thus enabling fully automated DNA amplification. Twenty-five amplification cycles increase the amount of target sequence by approximately 10 ⁇ -fold.
  • the polymerase chain reaction technique offers the advantage of an increased signal intensity in subsequent assays.
  • Devices for use in DNA polymerisation typically consist of a heat conductive material provided with channels adapted to receive vessels in which the reaction is to take place, typically Eppendorf tubes. The heat conductive material is then provided with heating/cooling means.
  • One of the main difficulties encountered in the use of such devices has been the achievement of relatively rapid cooling of the DNA reaction mixture.
  • the most common solution to this problem has been to use Peltier effect heat pumps to effect both the heating and the cooling of the reaction mixture.
  • the continual cycling between heating and cooling typically leads to the Peltier effect heat pumps failing.
  • the present inventor has developed a novel device which enables rapid heating and cooling of the DNA reaction mix whilst being relatively robust and economic to produce.
  • the present invention consists in a device for use in DNA polymerisation, the device comprising an element adapted to receive tubes in which the DNA polymerisation reaction is to take place and being provided with heating means adapted to heat the element, a heat sink adapted to remove heat from the element and movement means enabling the movement of the element and the heat sink into and out of contact with each other.
  • the present invention consists in a method of DNA amplification using polymerase chain reaction, the method being characterised in that a reaction mixture comprising DNA, suitable thermoscable DNA poly erases and oligonucleotide primers in a vessel is placed in an element adapted to receive the vessel, the element being provided with heating means, heating the reaction mixture by actuation of the heating means, stopping the heating means, cooling the reaction mixture by bringing a heat sink into contact with the element, moving the heat sink away from the element and cyclically repeating the heating and cooling steps.
  • the element remains stationary and the heat sink is moved into and out of contact with the element.
  • the mass of the heat sink is substantially greater than the mass of the element. It is presently preferred that the mass of the heat sink is two to three times the mass of the element.
  • the device is provided with means for cooling the heat sink. This cooling means may consist of a fan directed on the heat sink, Peltier effect coolers provided within the heat sink or other forms of cooling readily known in the art.
  • the movement of the element and/or the heat sink into and out of contact with each other is automated.
  • temperature sensing means is provided in the DNA reaction mixture.
  • the temperature sensing means is preferably connected to control means which controls the movement of the element and/or heat sink into and out of contact with each other. It is preferred that this automation is computer controlled.
  • the device 10 for use in DNA polymerisation comprises an element 12, a heat sink 14 and movement means 16.
  • the element 12 and heat sink 14 are made of material which is a good thermal conductor, such as metal.
  • the element 12 is provided with wells 18 adapted to receive tubes in which the DNA polymerisation reaction is to take place.
  • the element 12 is also provided with heat electric heating elements shown generally as 20.
  • the heat sink 14 is provided with cooling fins 22 to enable a greater dissipation of heat from the heat sink.
  • the cooling fins 22 are positioned above a fan 25 arranged such as to blow air onto the cooling fins 22 of the heat sink 14.
  • the heat sink 14 is also provided with Peltier effect coolers shown generally as 24.
  • the movement means 16 enables the movement of the heat sink 14 into and ⁇ t of contact with the element 12.
  • the movement means 16 consists of arm 26 connected at. end 28 to heat sink 14 and at end 30 to actuator 32.
  • the arm 26 is pivoted about point 34. Actuation of actuator 32 will result in the heat sink 14 being brought into contact with the element 12.
  • a reaction mixture of DNA, thermostable DNA polymerase and oligonucleotide primers in tubes are placed in wells 18 of element 12.
  • the electric heating elements 20 are then actuated to raise the temperature of the element 12 and consequently the temperature of the reaction mix in the tubes in wells 18.
  • the temperature is then maintained at a predetermined level, typically 93°C for a predetermined period of time, typically one and a half minutes.
  • the electric heater elements 20 are turned off and actuator 32 actuated resulting in bringing heat sink 14 into contact with element 12. As heat sink 14 is at a substantially lower temperature than element 12 heat is lost from element 12 to heat sink 14.
  • the reaction mixture is cooled to a predetermined temperature, typically 60°C and held at this temperature for a predetermined period of time, typically one and a half minutes.
  • a predetermined temperature typically 60°C and held at this temperature for a predetermined period of time, typically one and a half minutes.
  • the adsorption of heat from element 12 by heat sink 14 results in little raising of the temperature of heat sink 14.
  • heat is rapidly lost from the heat sink 14 due to the action of fan 25 directing air on cooling fins 22.
  • the temperature of the heat sink 14 may .also be lowered by Peltier coolers 24.
  • the actuator 32 is once again actuated and heat sink 14 is moved out of contact with element 12.
  • the electric heater elements are again actuated and the reaction mixture heated once again.
  • the device of the present invention has been shown to be capable of achieving the drop in temperature from 93°C to 60° in approximately thirty seconds without the use of the Peltier effect coolers. As will be appreciated by persons skilled in the art this is a substantial improvement over prior art devices.
  • the cyclic nature of the operation of the device of the present invention lends itself to computer automation.
  • the temperature of the element 12 and the DNA reaction mixture is monitored and the electric heating elements 20 cyclically actuated and the heat sink 14 cyclically brought into contact with the element 12 by means of movement means 16 to achieve cooling of the element 12 and consequently the reaction mixture.
  • DNA amplification procedures are typically run over an extended period of time to provide the required number of amplification cycles.
  • the computer can be programmed such that the heat sink 14 is brought into contact with the element 12 and the Peltier coolers 26 actuated to maintain the DNA reaction mixture at a predetermined temperature such as 4°C. Any risk of substantial denaturation of the amplified DNA would therefore be reduced.
  • the device of the present invention provides a relatively robust and simple alternative to devices of the prior art whilst providing a rapid means of cooling the DNA reaction mixture.

Abstract

The present invention provides a device for use in DNA polymerisation. The device comprises an element (12) adapted to receive tubes in which the DNA polymerisation reaction is to take place. The element (12) is provided with heating means (20) adapted to heat the element (12). The device also includes a heat sink (14) adapted to remove heat from the element (12) and movement means (16) enabling the movement of the element (12) and the heat sink (14) into and out of contact with each other.

Description

IMPROVED DNA POLYMERISATION DEVICE Field of the Invention
The present invention relates to a device for use in DNA polymerisation. Background of the Invention
In a number of applications, such as gene analysis and DNA fingerprinting, it is often necessary to multiply the amount of DNA present a sample. A DNA segment of up to approximately six thousand base pairs in length may be amplified exponentially starting from as little as a single gene copy by means of polymerised chain reaction.
In this technique a denatured DNA sample is incubated with two oligonucleotide primers that direct the DNA polymerase-dependent synthesis of complimentary strains. Multiple cycles of synthesis each afford an approximate doubling of the amount of target sequence. Each cycle is controlled by simply varying the temperature to permit denaturation of the DNA strands, annealing of the primers, and synthesis of new DNA strands. The use of a thermostable DNA polymerase obviates the necessity of adding new enzyme for each cycle, thus enabling fully automated DNA amplification. Twenty-five amplification cycles increase the amount of target sequence by approximately 10^-fold. For the purposes of gene analysis the polymerase chain reaction technique offers the advantage of an increased signal intensity in subsequent assays. More detailed information regarding the polymerase chain reaction can be found in "PCR Protocols - A Guide to Methods and Applications" Eds. M.A. Innis, D.H. Gelfard, J.J. Sainskey, T.J. White, Academic Press. Inc. San Diego 1990" the disclosure of which is incorporated herein by reference.
Devices for use in DNA polymerisation typically consist of a heat conductive material provided with channels adapted to receive vessels in which the reaction is to take place, typically Eppendorf tubes. The heat conductive material is then provided with heating/cooling means. One of the main difficulties encountered in the use of such devices has been the achievement of relatively rapid cooling of the DNA reaction mixture. The most common solution to this problem has been to use Peltier effect heat pumps to effect both the heating and the cooling of the reaction mixture. However, the continual cycling between heating and cooling typically leads to the Peltier effect heat pumps failing. Summary of the Invention
The present inventor has developed a novel device which enables rapid heating and cooling of the DNA reaction mix whilst being relatively robust and economic to produce.
Accordingly, in a first aspect the present invention consists in a device for use in DNA polymerisation, the device comprising an element adapted to receive tubes in which the DNA polymerisation reaction is to take place and being provided with heating means adapted to heat the element, a heat sink adapted to remove heat from the element and movement means enabling the movement of the element and the heat sink into and out of contact with each other. In a second aspect the present invention consists in a method of DNA amplification using polymerase chain reaction, the method being characterised in that a reaction mixture comprising DNA, suitable thermoscable DNA poly erases and oligonucleotide primers in a vessel is placed in an element adapted to receive the vessel, the element being provided with heating means, heating the reaction mixture by actuation of the heating means, stopping the heating means, cooling the reaction mixture by bringing a heat sink into contact with the element, moving the heat sink away from the element and cyclically repeating the heating and cooling steps.
In a preferred embodiment of the present invention the element remains stationary and the heat sink is moved into and out of contact with the element. In a further preferred embodiment of the present invention the mass of the heat sink is substantially greater than the mass of the element. It is presently preferred that the mass of the heat sink is two to three times the mass of the element. In yet a further preferred embodiment of the present invention the device is provided with means for cooling the heat sink. This cooling means may consist of a fan directed on the heat sink, Peltier effect coolers provided within the heat sink or other forms of cooling readily known in the art.
In yet another preferred embodiment of the present invention the movement of the element and/or the heat sink into and out of contact with each other is automated. Preferably, in operation, temperature sensing means is provided in the DNA reaction mixture. The temperature sensing means is preferably connected to control means which controls the movement of the element and/or heat sink into and out of contact with each other. It is preferred that this automation is computer controlled. Detailed Description of the Invention
In order that the nature of the present invention may be more clearly understood, a preferred form thereof will now be described with reference to the accompanying drawing, in which is shown a schematic representation of a preferred embodiment of the device of the present invention.
The device 10 for use in DNA polymerisation comprises an element 12, a heat sink 14 and movement means 16. The element 12 and heat sink 14 are made of material which is a good thermal conductor, such as metal. The element 12 is provided with wells 18 adapted to receive tubes in which the DNA polymerisation reaction is to take place. The element 12 is also provided with heat electric heating elements shown generally as 20. The heat sink 14 is provided with cooling fins 22 to enable a greater dissipation of heat from the heat sink. The cooling fins 22 are positioned above a fan 25 arranged such as to blow air onto the cooling fins 22 of the heat sink 14. The heat sink 14 is also provided with Peltier effect coolers shown generally as 24.
The movement means 16 enables the movement of the heat sink 14 into and αμt of contact with the element 12. The movement means 16 consists of arm 26 connected at. end 28 to heat sink 14 and at end 30 to actuator 32. The arm 26 is pivoted about point 34. Actuation of actuator 32 will result in the heat sink 14 being brought into contact with the element 12.
In order that the nature of the operation of the device of the present invention may be more clearly understood the operation of the device shown in the accompanying drawing will now be described.
A reaction mixture of DNA, thermostable DNA polymerase and oligonucleotide primers in tubes are placed in wells 18 of element 12. The electric heating elements 20 are then actuated to raise the temperature of the element 12 and consequently the temperature of the reaction mix in the tubes in wells 18. The temperature is then maintained at a predetermined level, typically 93°C for a predetermined period of time, typically one and a half minutes. At the end of the heating period the electric heater elements 20 are turned off and actuator 32 actuated resulting in bringing heat sink 14 into contact with element 12. As heat sink 14 is at a substantially lower temperature than element 12 heat is lost from element 12 to heat sink 14. The reaction mixture is cooled to a predetermined temperature, typically 60°C and held at this temperature for a predetermined period of time, typically one and a half minutes. Typically, given the substantially greater mass of the heat sink 14 in comparison to element 12, the adsorption of heat from element 12 by heat sink 14 results in little raising of the temperature of heat sink 14. In addition, heat is rapidly lost from the heat sink 14 due to the action of fan 25 directing air on cooling fins 22. In addition, the temperature of the heat sink 14 may .also be lowered by Peltier coolers 24.
At the end of the cooling step the actuator 32 is once again actuated and heat sink 14 is moved out of contact with element 12. At this time the electric heater elements are again actuated and the reaction mixture heated once again.
These steps are then cyclically repeated until the desired number of amplification steps are achieved. In use the device of the present invention has been shown to be capable of achieving the drop in temperature from 93°C to 60° in approximately thirty seconds without the use of the Peltier effect coolers. As will be appreciated by persons skilled in the art this is a substantial improvement over prior art devices.
As would be appreciated by persons skilled in the art the cyclic nature of the operation of the device of the present invention lends itself to computer automation. In such a situation the temperature of the element 12 and the DNA reaction mixture is monitored and the electric heating elements 20 cyclically actuated and the heat sink 14 cyclically brought into contact with the element 12 by means of movement means 16 to achieve cooling of the element 12 and consequently the reaction mixture. As would be appreciated by persons skilled in the art such DNA amplification procedures are typically run over an extended period of time to provide the required number of amplification cycles. If desired at the end of the required number of cycles, the computer can be programmed such that the heat sink 14 is brought into contact with the element 12 and the Peltier coolers 26 actuated to maintain the DNA reaction mixture at a predetermined temperature such as 4°C. Any risk of substantial denaturation of the amplified DNA would therefore be reduced.
As will be appreciated by persons skilled in the art the device of the present invention provides a relatively robust and simple alternative to devices of the prior art whilst providing a rapid means of cooling the DNA reaction mixture.
It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

CLAIMS: -
1. A device for use in DNA polymerisation, the device comprising an element adapted to receive tubes in which the DNA polymerisation reaction is to take place and being provided with heating means adapted to heat the element, a heat sink adapted to remove heat from the element and movement means enabling the movement of the element and the heat sink into and out of contact with each other.
2. A device as claimed in claim 1, in which the element remains stationary and the heat sink is moved into and out of contact with the element.
3. A device as claimed in claim 1 or 2 , in which the mass of the heat sink is substantially greater than the mass of the element.
4. A device as claimed in claim 3, in which the mass of the heat sink is two to three times the mass of the element.
5. A device as claimed in any one of claims 1 to , in which the heat sink is provided with cooling means selected from the group consisting of a fan directed on the heat sink, Peltier effect coolers provided within the heat sink or a combination thereof.
6. A method of DNA amplification using polymerase chain reaction, the method being characterized in that a reaction mixture comprising DNA, suitable thermostable DNA polymeraseε and oligo nucleotide primers in a vessel is placed in an element adapted to receive the vessel, the element being provided with heating means, heating the reaction mixture by actuation of the heating means, stopping the heating means, cooling the reaction mixture by bringing a heat sink into contact with the element, moving the heat sink away from the element and cyclically repeating the heating and cooling steps.
7. A method as claimed in claim 6, in which the element remains stationary and the heating sink is moved into and out of contact with the element.
8. A method as claimed in claim 6 or claim 7, in which the mass of the heat sink is substantially greater than the mass of the element.
9. A method as claimed in claim 8, in which the mass of the heat sink is two to three times the mass of the element.
10. A method as claimed in any one of claims 6 to 9, in which the heat sink is provided with cooling means selected from the group consisting of a fan directed on the heat sink, Peltier effect coolers provided within the heat sink and combinations thereof.
PCT/AU1990/000560 1989-11-21 1990-11-20 Improved dna polymerisation device WO1991007504A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPJ750589 1989-11-21
AUPJ7505 1989-11-21

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WO1991007504A1 true WO1991007504A1 (en) 1991-05-30

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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992020778A1 (en) * 1991-05-24 1992-11-26 Kindconi Pty Limited Biochemical reaction control
US5270183A (en) * 1991-02-08 1993-12-14 Beckman Research Institute Of The City Of Hope Device and method for the automated cycling of solutions between two or more temperatures
DE4409436A1 (en) * 1994-03-19 1995-09-21 Boehringer Mannheim Gmbh Process for processing nucleic acids
WO1996023249A1 (en) * 1995-01-23 1996-08-01 Marshall Biotechnology Limited Thermoregulator
WO1997010896A1 (en) * 1995-09-22 1997-03-27 Berlex Laboratories, Inc. Apparatus and process for multiple chemical reactions
WO1998006490A1 (en) * 1996-08-12 1998-02-19 Monsanto Company Solid phase organic synthesis device with pressure-regulated manifold
WO1998013137A1 (en) * 1996-09-27 1998-04-02 Glaxo Group Limited Systems and methods for the synthesis of organic compounds
US5792430A (en) * 1996-08-12 1998-08-11 Monsanto Company Solid phase organic synthesis device with pressure-regulated manifold
US5888830A (en) * 1995-09-22 1999-03-30 Berlex Laboratories, Inc. Apparatus and process for multiple chemical reactions
US6042789A (en) * 1996-10-23 2000-03-28 Glaxo Group Limited System for parallel synthesis of organic compounds
US6054325A (en) * 1996-12-02 2000-04-25 Glaxo Wellcom Inc. Method and apparatus for transferring and combining distinct chemical compositions with reagents
US6083761A (en) * 1996-12-02 2000-07-04 Glaxo Wellcome Inc. Method and apparatus for transferring and combining reagents
US6083682A (en) * 1997-12-19 2000-07-04 Glaxo Group Limited System and method for solid-phase parallel synthesis of a combinatorial collection of compounds
US6149869A (en) * 1996-10-23 2000-11-21 Glaxo Wellcome Inc. Chemical synthesizers
US6988546B1 (en) * 1999-11-26 2006-01-24 Eyela-Chino Inc. Sample temperature regulator

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU6918087A (en) * 1986-02-25 1987-08-27 Applera Corporation Apparatus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps
US4865986A (en) * 1988-10-06 1989-09-12 Coy Corporation Temperature control apparatus
DE3808942A1 (en) * 1988-03-17 1989-09-28 Bio Med Gmbh Ges Fuer Biotechn Incubator, in particular for the polymerase chain reaction
EP0342155A2 (en) * 1988-05-13 1989-11-15 Agrogen-Stiftung Laboratory device for optional heating and cooling
WO1989012502A1 (en) * 1988-06-23 1989-12-28 Lep Scientific Limited Biochemical reaction machine
DE3839162A1 (en) * 1988-11-19 1990-05-23 Arman Notghi Apparatus for the automatic adjustment of a plurality of temperature states in molecular biological methods

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU6918087A (en) * 1986-02-25 1987-08-27 Applera Corporation Apparatus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps
DE3808942A1 (en) * 1988-03-17 1989-09-28 Bio Med Gmbh Ges Fuer Biotechn Incubator, in particular for the polymerase chain reaction
EP0342155A2 (en) * 1988-05-13 1989-11-15 Agrogen-Stiftung Laboratory device for optional heating and cooling
WO1989012502A1 (en) * 1988-06-23 1989-12-28 Lep Scientific Limited Biochemical reaction machine
US4865986A (en) * 1988-10-06 1989-09-12 Coy Corporation Temperature control apparatus
DE3839162A1 (en) * 1988-11-19 1990-05-23 Arman Notghi Apparatus for the automatic adjustment of a plurality of temperature states in molecular biological methods

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BIO/TECHNOLOGY, Volume 6, No. 1, January 1988, page 82. *
BIO/TECHNOLOGY, Volume 6, No. 9, September 1988, page 1104. *
NATURE, Volume 331, 4 February 1988, pages 461-462, H.A. ERLICH et al., "Specific DNA Amplification". *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270183A (en) * 1991-02-08 1993-12-14 Beckman Research Institute Of The City Of Hope Device and method for the automated cycling of solutions between two or more temperatures
WO1992020778A1 (en) * 1991-05-24 1992-11-26 Kindconi Pty Limited Biochemical reaction control
DE4409436A1 (en) * 1994-03-19 1995-09-21 Boehringer Mannheim Gmbh Process for processing nucleic acids
WO1996023249A1 (en) * 1995-01-23 1996-08-01 Marshall Biotechnology Limited Thermoregulator
US6274091B1 (en) 1995-09-22 2001-08-14 Berlex Laboratories, Inc. Apparatus and process for multiple chemical reactions
WO1997010896A1 (en) * 1995-09-22 1997-03-27 Berlex Laboratories, Inc. Apparatus and process for multiple chemical reactions
US5888830A (en) * 1995-09-22 1999-03-30 Berlex Laboratories, Inc. Apparatus and process for multiple chemical reactions
WO1998006490A1 (en) * 1996-08-12 1998-02-19 Monsanto Company Solid phase organic synthesis device with pressure-regulated manifold
US5792430A (en) * 1996-08-12 1998-08-11 Monsanto Company Solid phase organic synthesis device with pressure-regulated manifold
WO1998013137A1 (en) * 1996-09-27 1998-04-02 Glaxo Group Limited Systems and methods for the synthesis of organic compounds
US5866342A (en) * 1996-09-27 1999-02-02 Glaxo Group Limited Systems and methods for the synthesis of organic compounds
US6042789A (en) * 1996-10-23 2000-03-28 Glaxo Group Limited System for parallel synthesis of organic compounds
US6117397A (en) * 1996-10-23 2000-09-12 Glaxo Group Limited System and methods for parallel synthesis of organic compounds
US6149869A (en) * 1996-10-23 2000-11-21 Glaxo Wellcome Inc. Chemical synthesizers
US6051439A (en) * 1996-10-23 2000-04-18 Glaxo Wellcome Inc. Methods for parallel synthesis of organic compounds
US6054325A (en) * 1996-12-02 2000-04-25 Glaxo Wellcom Inc. Method and apparatus for transferring and combining distinct chemical compositions with reagents
US6083761A (en) * 1996-12-02 2000-07-04 Glaxo Wellcome Inc. Method and apparatus for transferring and combining reagents
US6083682A (en) * 1997-12-19 2000-07-04 Glaxo Group Limited System and method for solid-phase parallel synthesis of a combinatorial collection of compounds
US6168914B1 (en) 1997-12-19 2001-01-02 Glaxo Wellcome Inc. System and method for solid-phase parallel synthesis of a combinatorial collection of compounds
US6988546B1 (en) * 1999-11-26 2006-01-24 Eyela-Chino Inc. Sample temperature regulator
US7182130B2 (en) 1999-11-26 2007-02-27 Eyela-Chino Inc. Sample temperature regulator

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