WO2010010361A1 - Améliorations dans un appareil réacteur - Google Patents

Améliorations dans un appareil réacteur Download PDF

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Publication number
WO2010010361A1
WO2010010361A1 PCT/GB2009/001838 GB2009001838W WO2010010361A1 WO 2010010361 A1 WO2010010361 A1 WO 2010010361A1 GB 2009001838 W GB2009001838 W GB 2009001838W WO 2010010361 A1 WO2010010361 A1 WO 2010010361A1
Authority
WO
WIPO (PCT)
Prior art keywords
hrm
reaction
heating element
vessel
heater
Prior art date
Application number
PCT/GB2009/001838
Other languages
English (en)
Inventor
David Ward
Nelson Nazareth
Original Assignee
Bg Research 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 Bg Research Ltd filed Critical Bg Research Ltd
Priority to GB1100525.3A priority Critical patent/GB2474163B/en
Publication of WO2010010361A1 publication Critical patent/WO2010010361A1/fr

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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
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • B01L2300/185—Means for temperature control using fluid heat transfer medium using a liquid as fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1883—Means for temperature control using thermal insulation

Definitions

  • the invention relates to biological or chemical reactions, particularly those carried out at the nanolitre to microlitre level, and may even include those carried out at the picolitre level. It includes those involving thermal cycling such as polymerase chain reactions (PCR) as well as isothermal reactions.
  • PCR polymerase chain reactions
  • reaction vessels may be in the form of a tray, known as a microtitre plate, made up of an array of vessels, (n one standard microtitre plate, 96 vessels are formed in one array. Indeed often such plates are constructed on a 96 x n basis, where n is an integer. 96 incidentally tends to mean an array of 12 by 8 rows.
  • PCT Patent Application PCT/GB08/00775 describes such apparatus but in which a Peltier device is employed as a medium to effect both heating and cooling in consort with a heat removal module (HRM) which is itself described and claimed as such in PCT Patent Application PCT/GB07/003564.
  • HRM heat removal module
  • This enables very rapid heat transfer to and from the reactants.
  • Peltier devices are quite expensive, which is particularly noticeable where an individual such device is designated for each station in a 96n array device.
  • apparatus for effecting a chemical or biological reaction comprises: a heat removal module as described in Patent Application PCT/GB07/003564, namely a module comprising a thermally conductive material having therein a channel adapted for the flow of a coolant liquid, a heating element mounted upon the HRM; and a layer of thermally insulative material between the HRM and the heater, the thermally insulative material having the property of restricting heat loss from the heating element into the HRM while the heating element is in heating mode while permitting heat transfer thereacross when the heating element is not in heating mode.
  • a heat removal module as described in Patent Application PCT/GB07/003564, namely a module comprising a thermally conductive material having therein a channel adapted for the flow of a coolant liquid, a heating element mounted upon the HRM; and a layer of thermally insulative material between the HRM and the heater, the thermally insulative material having the property of restricting heat loss from the heating element into the HRM while the heating element is in heating
  • apparatus according to the present invention Whilst the time within which a reaction cycle involving heating and cooling using apparatus according to the present invention may be somewhat longer than when using apparatus incorporating Peltier devices as described in PCT Patent Application PCT/GB08/000775, apparatus according to the present invention stands to be considerably less expensive for a time cost which may not be excessive or unacceptable.
  • a thermally conductive cup is mounted above the heating element, the cup being constructed to receive a reaction vessel in which the reaction is to occur.
  • the apparatus comprises a HRM upon which is mounted a plurality of heating elements via the said insulative layer in an array, each heating element carrying one or a plurality of said cups. In this way the heating elements may, if desired be individually controlled.
  • the speed of heat loss to the heat removal module can be varied. In this way when heat is generated by the heater mat and the heat input is greater than lost to the heat removal module the temperature inside the reaction vessel will increase. Where the heater is inputting less heat to the reaction cup than is being dissipated by the heat removal module the temperature in the reaction vessel will decrease.
  • the thermal insulation layer material may be silicon although Aluminium oxide, Aluminium Nitride, Aluminium, Graphite or a loaded polymer; commercial products such as thermal clad supplied by the Bergquist company or Denka are also suited this purpose.
  • the choice of this material and the thickness thereof is made according to the desired heat transfer rates.
  • the HRM is advantageously a block of highly thermally conductive metal with the channels therein in labyrinthine or serpentine form whereby the coolant liquid may flow adjacent to one or a plurality of reaction vessels.
  • HRM is formed of two mating plates and the labyrinth is formed in one or both of the mating surfaces, for example by milling or routing.
  • a suitable sealant may be used to ensure no escape of the coolant.
  • the sealant may also be required to insulate one plate from the other electrically.
  • the HRM is formed of a single block and the labyrinth by drilling therethrough, and then blocking any unwanted exits or routes using stoppers such as grub screws.
  • the material the block is formed of can depend upon the context and ease of use and economic considerations, with copper, aluminium alloy, silver, or gold, boron nitride, diamond and graphite among the possibilities. Where electrical insulation of the block is required the metal may be anodised.
  • the coolant liquid may be water, preferably a deionised water with an antioxidant addition.
  • a typical example is FluidXP ⁇ supplied by Integrity PC Systems & Technologies, Inc. USA.
  • the heater element may be formed as part of a printed circuit and comprise an aluminium or copper plate for example.
  • a heat dissipation layer may be included between the heater element and the cup to ensure an even transfer of here therethrough.
  • This may comprise a layer of thermally conductive adhesive.
  • the adhesive is a loaded epoxy such as a silver loaded adhesive (an example of a suitable adhesive is Emmerson Cummings part number 57C which is a multipart adhesive loaded with solvent).
  • the heat dissipation layer may be any thermally conductive adhesive with a thermal conductivity greater than 1.5 W/mK. Additionally and when the heater and cup iteration allows, the cup holder may be soldered to the heater.
  • the cup may be formed of metal and may have a vessel portion arranged to receive snugly a reaction vessel and a base portion arranged to be contiguous and coterminous with the associated heater element.
  • the wall of the vessel portion may taper down in thickness toward the upper rim thereof.
  • the bottom of the vessel portion is preferably arranged to receive a temperature sensor.
  • a suitable reaction vessel is formed from a thermally conductive material, that is for example a plastics material loaded with a carbon.
  • the apparatus may also comprise a heat sink associated with the HRM, as described in Patent Application PCT/GB07/003564 and optica! sensing apparatus
  • an optical monitoring system for a reaction apparatus where the reaction apparatus defines a plurality of receiving stations, each such station receiving a reaction vessel in which a reaction may take place.
  • the optical monitoring system may comprise at least one radiation source. Also provided is a scanning apparatus for directing radiation to vessels in the receiving stations, and for directing radiation emitted by the reaction vessel contents into photometric apparatus.
  • the photometric apparatus directs received radiation to a diffraction grating or equivalent technology, and thence to a single or plurality wavelength optical detector, such as a Photon Multiplier Tube or Avalanche Photo Diode preferably operating in photon counting mode.
  • the photomultipiier tube assembly may comprise a series of single channel multi- anode photomultiplier tubes but preferably the assembly comprises a multichannel multi-anode photomultiplier tube (MAPMT) or a multi detector Avalanche photodiode array (APD).
  • MAPMT multichannel multi-anode photomultiplier tube
  • APD multi detector Avalanche photodiode array
  • Radiation emitted by the vessel contents is dispersed over the pixels of the MAPMT or APD by means of a diffraction grating such that the range of wavelengths of radiation impinging upon a photocathode of the multi-anode photomultiplier tube correlates with the position of the photocathode in the MAPMT or a detector of the APD.
  • the MAPMT or APD is a 32 pixel linear array over which radiation from around 510-720 nm is dispersed.
  • the optical monitoring system provides for the use of a broad range of fluorophores emitting radiation at wavelengths between about 510nm and about 720nm without the need to change filter sets as required in other instrumentation.
  • the use of the PMT or APD and operating it in photon counting mode provides for sensitive detection of radiation facilitating the measurements of low levels of incident fluorescence associated with high sampling frequencies. Measurements using a PMT and APD operating in photon counting mode are less affected by changes in the electromagnetic environment, than if the PMT is operated in analogue mode, however the analogue reading mode may be advantageous in certain applications.
  • the optical monitoring means is preferably an integral part of the reaction apparatus. . . - ⁇
  • the light source is a single light source, typically a laser or light emitting diode.
  • the laser is a diode pumped solid-state laser (DPSSL) in contrast to the gas lasers used in conventional reaction apparatus and optical monitoring systems.
  • DPSSL diode pumped solid-state laser
  • Preferably means are provided for monitoring the reactions within a plurality of tubes, by directing radiation from a single excitation source to the tubes, and collecting the resultant radiation from the tubes to be measured by a single photometric system.
  • This means may comprise one or more rotatable mirrors, where the configuration of mirrors can be controlled to direct light to and from any specific tube. An array of two mirrors is preferred. The size and bulk of the mirror is arranged to be such as to achieve efficient radiation collection with minimum scanning frequency.
  • the acquisition of a full spectrum from each vessel at each sampling point facilitates the concurrent use of multiple different fluorophores in the array of reaction vessels in the apparatus (including use of multiple different fluorophores within a single vessel) as required by some fluorometric applications.
  • This spectrum may also be acquired in a single operation reading all channels of the
  • MAPMT or APD concurrently, in contrast to systems where readings at different wavelengths must be acquired consecutively, for example by use of a filter wheel or other means. This affords higher sampling rates, and removes effects related to variation in signal between the acquisitions of different wavelengths.
  • a Fresnel lens may be used in the path of the laser.
  • a Fresnel lens is light, cost- effective and very compact compared to a standard lens of the same diameter and optical properties.
  • the Fresnel lens ensures that the radiation from the excitation source is always directed substantially vertically when it enters each vessel.
  • the rotating mirrors cause the beam to be reflected at an angle, such that it hits the Fresnel lens at a point above the vessel to be illuminated, the Fresnel lens refracts the beam from this point to enter the vessel vertically.
  • the resultant emitted radiation from the vessel is refracted from vertical travel to the correct angle to return to the rotating mirrors and hence to the photometric system.
  • a plurality of light sources may be used as the excitation source to illuminate the sample with a variation of radiation spectra.
  • the excitation sources may be a plurality of individually attenuated LASERs, a plurality of Light Emitting Diodes, a Light Emitting Diode (LED) capable of generating a variety of spectra (RGB LED's) or multiple incandescent or fluorescent lamps.
  • Software and/or physical filters may be used to remove incident light from the detected sample spectra and also to remove emissions resultant from excitation from one source from those resultant from another source and in this way allow non source-specific emissions to be subtracted and experimentally link fluorophores in the reaction to specific light sources as discussed above. This allows the apparatus to excite at a number of individual wavelengths simultaneously while removing the necessity to change filters using a filter wheel. Where single excitation sources are used a physical filter may be used to remove the excitation spectra from the detected sample spectra. Filter Wheels are generally regarded as slow devices capable of performing several colour changes per second. The use of the software filtering allows up to 1500 samples per second to be filtered. As to detection, CCD, a photomultiplier tube or an avalanche photo diode array are among the possibilities.
  • An alternative optical monitor system comprises a printed circuit board (PCB) arranged for presentation above the reaction vessels, the PCB holding an array of light emitting diodes (LEDs) selected so as to be within the excitation spectrum of the vessel contents under interrogation and arranged for the direction of light into the vessel, the PCB also having a foramen arranged to permit the passage of vessel content light emission spectra, the system also comprising detector apparatus arranged to detect the emission spectra and filter means to block the path of excitation spectra to the detector.
  • PCB printed circuit board
  • LEDs light emitting diodes
  • the LEDs are arranged to emit light at the blue end of the optical spectrum, typically at a wavelength of 470nm or above.
  • One suitable detector apparatus may comprise a fresnel lens arranged to direct the light onto an XY scanning mirror set and thereby into a detector such as a PMT, APD (avalanche photo-diode), CCD (charge couple device), LDR (light dependent resistor) or a photovoltaic cell.
  • the PMT may be single cell or, if the emission beam is split into a spectrum, an array thereof.
  • the filter means may comprise an optical filter placed for example across the foramen or software associated with the detector. Where, as will usually be the case, there is a lid to the vessel the optical monitor system is arranged for light path association therewith.
  • the invention also comprises a chemical or biological reaction carried out in apparatus as described above.
  • Figure 1 is a schematic cross section of a part of an apparatus for effecting a biochemical reaction
  • Figure 2 is a schematic cross section of a HRM
  • Figure 3 illustrates optical sensor equipment incorporated in the apparatus.
  • the apparatus shewn in figure 1 comprises a heat removal module (HRM) 10 upon which is mounted a heater element array 11 , via a silicon insulative layer 12.
  • HRM heat removal module
  • An array of cups 13 is mounted on the heater element array 11 via thermally conductive adhesive 14.
  • the HRM is as described in PCT Patent Application PCT/GB07/003564. It comprises a substantially rectangular metal block having formed therein an array of channels 21 which are formed into a labyrinth by a plurality of grub screws 22.
  • the block is such as to define an array of vessel stations and the channel labyrinth is formed so that there is a channel 21 adjacent every vessel station.
  • the module is formed of aluminium and provides vessel stations for a standard microtitre array, that is a 12 x 8 array at 9mm centres.
  • the channels 21 have a 3mm bore.
  • the module is anodised so as to have an insulative surface.
  • the HRM channels 21 are connected via a pump to a heat sink in which coolant liquid is maintained at a constant temperature just below the lowest temperature employed in the reactions carried out in the vessels.
  • the coolant is the deionised water with an antioxidant addition, FluidXP ⁇ supplied by Integrity PC Systems & Technologies, Inc. USA.
  • the HRM is consequently maintained at a temperature below the desired vessel temperature to allow the subsequent cooling step to take place at the required rate, and preferably at above 6C per second.
  • the low temperature and high thermal mass of the HRM ensures that there is no thermal cross-talk between wells.
  • the heater element array 11 comprises a printed circuit board (PCP) etched to provide an array of distinct heater elements with a distinct electrical supply to each and a common earth.
  • PCP printed circuit board
  • the cups 13 are formed of metal and are formed to hold snugly reaction vessels 30.
  • the cups have a side wall which tapers down in thickness upwards and a broad flat base by which they are mounted to the heater elements 11. Adjacent their base is a hole through which are connections to a temperature sensor (not shewn) disposed in the bottom thereof.
  • the thermally conductive adhesive 14 is a silver loaded adhesive namely Emmerson Cummings part number 57C which is a multipart adhesive loaded with solvent with a thermal conductivity greater than 1.5W/mK.
  • the reaction vessels 30 comprise a reaction chamber 31 and a lid retaining shank 32. They are formed from polypropylene loaded with more than 1 % by weight powdered carbon and have a wall thickness of less than 2mm. They are attached one to another to form a matrix defining the array corresponding to that of the cups 13.
  • the apparatus includes mechanisms for accepting, and removing, a vessel matrix preloaded with reactants and each sealed with a translucent lid.
  • the lid has a nose which projects into the body of the vessel, the tip of the nose defining a window through which light may pass for optical monitoring of the vessel contents.
  • the cup wall extends to adjacent the lid window such that the lid window is heated. This reduces the possibility of condensation formation, and thus allows for accurate and reproducible optical monitoring of the reactions occurring within the vessel.
  • the temperature sensors at the bottom of the cups form part of an electrical circuit which includes control switches, a power supply and the heating elements 11.
  • An optical monitoring system for the reaction apparatus is illustrated in figure 3.
  • the system comprises at least one light source 71 , scanning apparatus 79 for directing the light to the reaction vessels 69 in the receiving stations and for receiving radiation emitted by the reaction vessels and directing the radiation via a diffraction grating 73 to a multi-anode photomultiplier tube assembly 75 operating in a photon counting mode.
  • a foraminous mirror 93 contains a foramen at 45 degrees to the plane of the mirror, permitting laser light to pass through it to the vessels. The majority of diverging emitted light from the vessels is reflected to the diffraction grating 73, since at this point the emitted light beam is of much greater diameter than the foramen.
  • the multi-anode photomultiplier tube assembly 75 here comprises a multi-anode photomultiplier tube (MAPMT) with a 32 pixel array over which radiation from around 510 to 720 nm is dispersed. Radiation emitted by the reaction vessel contents is dispersed over the pixels of the MAPMT by the diffraction grating 73 such that the wavelength range of the radiation impinging on a photocathode of the MAPMT correlates with the position of the photocathode in the MAPMT.
  • MAPMT multi-anode photomultiplier tube
  • the light source 71 is a diode pumped solid state laser (DPSS Laser) which is smaller and lighter than conventional gas lasers typically used in optical monitoring systems.
  • DPSS Laser diode pumped solid state laser
  • the scanning apparatus comprises one or more planar rotatable mirrors, for clarity only one such mirror 79 is illustrated. These are motor driven and controlled by means which are omitted from the drawings for clarity.
  • the system of mirrors can be configured to direct the light from the laser to any receiving station. Radiation emitted is returned to foraminous mirror 93 which reflects the majority of the emitted radiation through lens 81 which focuses the radiation upon diffraction grating 73.
  • a Fresnel lens 83 is interposed between the rotatable mirrors, e.g. mirror 79, and the receiving stations to ensure verticality of the light entering each reaction vessel 69.
  • FIG. 6 An alternative embodiment of the optical arrangement is illustrated in figure 6.
  • a printed circuit board (PCB) is presented to the reaction vessel lids 100, the PCB holding an array of light emitting diodes (LED) selected to emit light at 470nm and arranged for the light thereof to be directed through the translucent portion of the lid 100.
  • a foramen 101 in the PCB is fitted with an optical filter 102 whereby only emission spectra and not excitation spectra is allowed to pass.
  • a fresnel lens 103 direct the light emerging from the vessels onto a detector 104 in the form of a photomultiplier tube (PMT).
  • PMT photomultiplier tube
  • Using the apparatus of the present invention to carry out a polymer chain reaction DNA amplification process comprises the steps of:

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne un appareil servant à réaliser une réaction chimique ou biologique comprenant : un module d'élimination de chaleur comprenant un matériau thermiquement conducteur contenant un conduit conçu pour l'écoulement d'un liquide de refroidissement, un élément chauffant monté sur le module d'élimination de chaleur, et une couche de matériau thermiquement isolant entre le module d'élimination de chaleur et le chauffage. Le matériau thermiquement isolant présente la propriété de limiter la perte de chaleur par l'élément chauffant dans le module d'élimination de chaleur lorsque l'élément chauffant est en mode de chauffage, en permettant cependant le transfert de chaleur à travers lui lorsque l'élément chauffant n'est pas en mode de chauffage.
PCT/GB2009/001838 2008-07-24 2009-07-23 Améliorations dans un appareil réacteur WO2010010361A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB1100525.3A GB2474163B (en) 2008-07-24 2009-07-23 Improvements in reactor apparatus

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0813562.6 2008-07-24
GBGB0813562.6A GB0813562D0 (en) 2008-07-24 2008-07-24 Improvements in reactor apparatus

Publications (1)

Publication Number Publication Date
WO2010010361A1 true WO2010010361A1 (fr) 2010-01-28

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PCT/GB2009/001838 WO2010010361A1 (fr) 2008-07-24 2009-07-23 Améliorations dans un appareil réacteur

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GB (2) GB0813562D0 (fr)
WO (1) WO2010010361A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012063011A3 (fr) * 2010-11-08 2012-08-02 Bg Research Ltd Chauffage et refroidissement de cuves à réaction biologique à faible volume

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5939312A (en) * 1995-05-24 1999-08-17 Biometra Biomedizinische Analytik Gmbh Miniaturized multi-chamber thermocycler
WO2001008800A1 (fr) * 1999-07-30 2001-02-08 Bio-Rad Laboratories, Inc. Regulation de la temperature pour un appareil de reaction a cuves multiples
US20020155036A1 (en) * 1998-08-13 2002-10-24 Symyx Technologies, Inc. Multi-temperature modular reactor and method of using same
US6572828B1 (en) * 1999-07-16 2003-06-03 General Electric Company Method and apparatus for high-throughput chemical screening
WO2007138302A1 (fr) * 2006-05-26 2007-12-06 Bg Research Ltd problÈmes de performances dans l'utilisation de rÉcipients pour des applications biologiques
US20070295705A1 (en) * 2004-05-24 2007-12-27 Andreas Geisbauer Tempering Methods and Tempering Device for the Thermal Treatment of Small Amounts of Liquid
EP1878502A1 (fr) * 2006-07-14 2008-01-16 Roche Diagnostics GmbH Appareil pour le chauffage et le refroidissement
US20080064086A1 (en) * 2006-09-13 2008-03-13 Electronics And Telecommunications Research Institute Plastic-based microfabricated thermal device, manufacturing method thereof, dna amplification chip using the plastic-based microfabricated thermal device, and method for manufacturing the dna amplification chip
WO2008107683A2 (fr) * 2007-03-08 2008-09-12 Bg Research Ltd Appareil et procédé de cyclage thermique

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5939312A (en) * 1995-05-24 1999-08-17 Biometra Biomedizinische Analytik Gmbh Miniaturized multi-chamber thermocycler
US20020155036A1 (en) * 1998-08-13 2002-10-24 Symyx Technologies, Inc. Multi-temperature modular reactor and method of using same
US6572828B1 (en) * 1999-07-16 2003-06-03 General Electric Company Method and apparatus for high-throughput chemical screening
WO2001008800A1 (fr) * 1999-07-30 2001-02-08 Bio-Rad Laboratories, Inc. Regulation de la temperature pour un appareil de reaction a cuves multiples
US20070295705A1 (en) * 2004-05-24 2007-12-27 Andreas Geisbauer Tempering Methods and Tempering Device for the Thermal Treatment of Small Amounts of Liquid
WO2007138302A1 (fr) * 2006-05-26 2007-12-06 Bg Research Ltd problÈmes de performances dans l'utilisation de rÉcipients pour des applications biologiques
EP1878502A1 (fr) * 2006-07-14 2008-01-16 Roche Diagnostics GmbH Appareil pour le chauffage et le refroidissement
US20080064086A1 (en) * 2006-09-13 2008-03-13 Electronics And Telecommunications Research Institute Plastic-based microfabricated thermal device, manufacturing method thereof, dna amplification chip using the plastic-based microfabricated thermal device, and method for manufacturing the dna amplification chip
WO2008107683A2 (fr) * 2007-03-08 2008-09-12 Bg Research Ltd Appareil et procédé de cyclage thermique

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012063011A3 (fr) * 2010-11-08 2012-08-02 Bg Research Ltd Chauffage et refroidissement de cuves à réaction biologique à faible volume

Also Published As

Publication number Publication date
GB0813562D0 (en) 2008-09-03
GB2474163B (en) 2013-04-10
GB201100525D0 (en) 2011-03-02
GB2474163A (en) 2011-04-06

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