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WO1993009486A1 - Dispositif permettant de reguler la temperature d'une reaction - Google Patents

Dispositif permettant de reguler la temperature d'une reaction Download PDF

Info

Publication number
WO1993009486A1
WO1993009486A1 PCT/GB1992/001996 GB9201996W WO9309486A1 WO 1993009486 A1 WO1993009486 A1 WO 1993009486A1 GB 9201996 W GB9201996 W GB 9201996W WO 9309486 A1 WO9309486 A1 WO 9309486A1
Authority
WO
WIPO (PCT)
Prior art keywords
block
samples
temperature
heater
heating
Prior art date
Application number
PCT/GB1992/001996
Other languages
English (en)
Inventor
Mark Ebdon
Arthur John Pinkney
Original Assignee
Hybaid Limited
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 Hybaid Limited filed Critical Hybaid Limited
Publication of WO1993009486A1 publication Critical patent/WO1993009486A1/fr

Links

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
    • B01J19/0006—Controlling or regulating processes
    • B01J19/0013—Controlling the temperature of the process
    • 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
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00054—Controlling or regulating the heat exchange system
    • B01J2219/00056—Controlling or regulating the heat exchange system involving measured parameters
    • B01J2219/00058—Temperature measurement
    • B01J2219/00063—Temperature measurement of the reactants
    • 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
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00132—Controlling the temperature using electric heating or cooling elements

Definitions

  • the present invention relates to temperature control devices, and in particular to devices for controlling the temperature of substances undergoing chemical reaction.
  • Such a temperature control device is described in International Patent Application No. WO/PCT/GB89/00323 (DEAN and EVANS) .
  • This Application discloses a device for controlling the temperature of a plurality of samples of a reacting mixture, comprising a heater block for receiving said samples, means for heating the block, means for cooling the block by forced convection, and temperature sensing means to monitor the temperature of one or more samples and signal a controller which controls the means for heating and the means for cooling to regulate the sample temperature.
  • the block is heated by a quartz-halogen lamp directly below the block which gives out radiant heat. This is directional and because of this the heating of the block is not always uniform. This can result in hot spots and limits the number of samples the device can hold.
  • a first aspect of the invention provides a device for controlling the temperature of a plurality of samples of a reacting mixture, comprising a heater block for receiving said samples, means for heating the block, means for cooling the block by forced convection, and temperature sensing means to monitor the temperature of one or more samples and signal a controller which controls the means for heating and the means for cooling to regulate the sample temperature, characterised in that the means for heating the block comprise one or more heater elements positioned in thermal contact with the block so that heat transfer between the elemen (s) and the block is substantially by conduction.
  • the known device is cooled by a fan under the block.
  • the location of the lamp means that the fan must be positioned to one side of the block. This causes uneven cooling of the test tubes.
  • the means for cooling the block by forced convection comprises a fan that is positioned under the centre of the block.
  • the block is made from a drilled sheet of copper in which copper tubes are soldered. This makes the block difficult and expensive to construct. Furthermore the soldered joints can disrupt heat conduction.
  • the block is made of solid metal.
  • the block can be easily made by electroforming .
  • thermocouples which limits the accuracy of the temperature control and necessitates periodic recalibration of the controller.
  • the temperature sensing means comprises one or more thermistors.
  • Fig.l is a vertical section through a control device according to a first embodiment of the present invention.
  • Fig.2 is a horizontal section through a part of the heater block comprising part of the first embodiment; and Fig.3 is a vertical section through a second embodiment of the invention.
  • the device comprises a casing 10, a rectangular heater block 20, a heater block support 40, a fan 50, and a collar 60.
  • the device further comprises a controller and temperature sensing means which are not shown in the drawings.
  • the heater block 20 is electroformed and comprises a single continuous layer of silver.
  • the block contains ninety six recesses 21 into which small test tubes (not shown in drawings) containing the reactant mixture are inserted.
  • the recesses form projections on the underneath of the block.
  • the arrangement of the recesses conforms with that of a standard size ninety six well microtitre dish (126 mm x 86 mm nominal) .
  • the heater block 20 is heated by a serpentine electric element 22 that extends between the recesses.
  • the element winds back and forth along the rows of recesses 21.
  • the element 22 is formed from a sheathed conductor.
  • the underside of the heater block 20 is cooled by a fan 50.
  • the outlet 51 of the fan is directed towards the centre underneath the heater block.
  • the heater block 20 is supported by the heater block support 40 which is plastic and which is supported by the casing 10.
  • the plastic collar 60 forms part of and hangs from the support 40.
  • the device is controlled by a controller that is responsive to two thermistor units placed one in thermal contact with the recesses 21 underneath the block, and another in a, dummy test tube within a recess.
  • the device particularly the support 40 and collar 60, is configured to provide an even airflow over the base of the heater block 20, to ensure uniform cooling of the samples.
  • the airflow path is indicated by arrows in Fig.l.
  • Louvres 11 are provided in the casing 10 to allow hot air to escape.
  • the device is particularly suited to undertaking biochemical reactions.
  • the reactant samples are contained in polypropylene sample tubes which each contain a sample of about 100 icro quantities.
  • the tubes are inserted into the recesses and can be filled in situ using a multiheaded pipette.
  • the device can achieve block heating and cooling rates of 3°C/sec and 2°C/sec respectively, which correspond to a sample heating or cooling rate of 1.2°C/sec.
  • the degree of control of the device allows it to perform ligase chain reactions.
  • the sample tubes can be made in glass. This enhances heat transfer to the samples.
  • sample tubes can be replaced with sealed 0.5 microlitre microfuge tubes. As these are larger than the standard sample tubes, only every other recess is used.
  • the device shown in Fig.3 is for heating samples that are held on microscope slides. Each sample is held between a slide 70 and a cover 71.
  • the device comprises two heater blocks 80, each comprising a continuous sheet of metal 81 that is supported by a casing 84 and that is overlaid by a serpentine electric element 82.
  • a flat sheet of aluminium 83 lies over each element and it is on this that the slides 70 lie.
  • the slides 70 are covered by a housing 90 that is used to place samples on .the blocks 80 for heating and remove them after heating.
  • the housing comprises edge support members 91 that engage the ends of the slides when the housing is lifted.
  • the edge support members define two rectangular apertures in plan view which can each support a number of slides. Each aperture contains locating means (not shown in Fig.3) which ensure the slides are kept in a regular arrangement and do not move about.
  • the structure of the housing is completed by a lid member 92 having a support 93. The whole structure forms a humidity chamber when the lid member 91 is in place.
  • a number of housings can be loaded in preparation for sample heating. As the housing is lowered over the device the slides 70 become supported on the aluminium sheets 83. The housing is further lowered until the lid member 92 rests on the edge of the casing 84 in the position shown in Fig.3. The samples are then heated in the required manner. When heating is completed the housing is lifted away from the casing and the slides
  • the type of heating element 22 can be varied.
  • a plurality of elements can replace the serpentine element.
  • a woven conductive cloth can be incorporated in the heater block.
  • a number of modifications can be made to the devices described.
  • a number of devices can be incorporated into a single unit for dealing with a larger number of samples.
  • a single unit incorporates four heating blocks of the type described. All four blocks are controlled by a single controller but measurements are only taken from a single heating block as representative of all the blocks. Such a unit is only workable because of the high degree of uniformity achievable in the heating of each block.
  • the devices have many advantages over known devices.
  • the temperature of different samples at different positions cross the heater block 20 have a high degree of uniformity. The effect of this is to improve the uniformity of product from the sample tubes. This in turn allows more samples to be accommodated in a single heater block (ninety six compared with seventy two in the cited prior device) . This also reduces the energy consumption of the device.
  • the uniformity of heating to the sample tubes is also enhanced by making the heater block in silver, which has a high thermal conductivity, and by employing a jointless construction.
  • the use of a solid silver block rather than a soldered copper block enhances heat transfer through the block. By eliminating the difficult soldering operations the cost of the block is reduced.
  • Incorporating the heating means into the heater block, rather than using a radiant heater, allows the fan to be positioned under the centre of the block. This results in an even airflow pattern over all parts of the block. The configuration of the airflow path eliminates dead spots where the cooling effect would be reduced.
  • thermocouples for temperature sensing rather than thermocouples increases the accuracy of operation and eliminates the need to periodically recalibrate the controller.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automation & Control Theory (AREA)
  • Physics & Mathematics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Clinical Laboratory Science (AREA)
  • Devices For Use In Laboratory Experiments (AREA)

Abstract

Dispositif de régulation de température comprenant un bloc de chauffage (20) formé à partir d'une couche de métal continue qui est chauffée par conduction grâce à un élément de chauffage (22) en contact thermique avec le bloc, et refroidie par un ventilateur (50) situé sous le bloc. La surface supérieure du bloc peut comporter des zones plates destinées à recevoir des prélèvements sur des lames porte-objets ou elle peut présenter des évidements (21) destinés à maintenir des prélèvements dans des éprouvettes de petite taille.
PCT/GB1992/001996 1991-11-05 1992-11-02 Dispositif permettant de reguler la temperature d'une reaction WO1993009486A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB919123463A GB9123463D0 (en) 1991-11-05 1991-11-05 Reaction temperature control device
GB9123463.3 1991-11-05

Publications (1)

Publication Number Publication Date
WO1993009486A1 true WO1993009486A1 (fr) 1993-05-13

Family

ID=10704095

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1992/001996 WO1993009486A1 (fr) 1991-11-05 1992-11-02 Dispositif permettant de reguler la temperature d'une reaction

Country Status (3)

Country Link
AU (1) AU2804792A (fr)
GB (1) GB9123463D0 (fr)
WO (1) WO1993009486A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997021834A1 (fr) * 1995-12-08 1997-06-19 Mj Research, Inc. Magasin pour cartouches d'echantillons en tiroirs
EP0863213A1 (fr) * 1991-07-23 1998-09-09 F. Hoffmann-La Roche Ag Equipement à cycles thermiques
WO1998043740A3 (fr) * 1997-03-28 1998-12-17 Perkin Elmer Corp Ameliorations apportees a un cycleur thermique pour pcr
WO1999044032A1 (fr) * 1998-02-27 1999-09-02 Cytologix Corporation Appareil de coloration de lames a acces selectif avec regulation thermique individuelle des lames
US6096271A (en) * 1998-02-27 2000-08-01 Cytologix Corporation Random access slide stainer with liquid waste segregation
DE19948641A1 (de) * 1999-10-06 2001-05-10 Imb Inst Fuer Molekulare Biote Kühleinrichtung für Mikrotiterplatten-Photometer
US6296809B1 (en) 1998-02-27 2001-10-02 Ventana Medical Systems, Inc. Automated molecular pathology apparatus having independent slide heaters
US6544798B1 (en) 1999-02-26 2003-04-08 Ventana Medical Systems, Inc. Removal of embedding media from biological samples and cell conditioning on automated staining instruments
US6582962B1 (en) 1998-02-27 2003-06-24 Ventana Medical Systems, Inc. Automated molecular pathology apparatus having independent slide heaters
US6855559B1 (en) 1998-09-03 2005-02-15 Ventana Medical Systems, Inc. Removal of embedding media from biological samples and cell conditioning on automated staining instruments
US6855552B2 (en) 1998-09-03 2005-02-15 Ventana Medical Systems Automated immunohistochemical and in situ hybridization assay formulations
US7133726B1 (en) 1997-03-28 2006-11-07 Applera Corporation Thermal cycler for PCR
US7378055B2 (en) 2002-04-26 2008-05-27 Ventana Medical Systems, Inc. Automated molecular pathology apparatus having fixed slide platforms
US7410753B2 (en) 1998-09-03 2008-08-12 Ventana Medical Systems, Inc. Removal of embedding media from biological samples and cell conditioning on automated staining instruments
US7425306B1 (en) 2001-09-11 2008-09-16 Ventana Medical Systems, Inc. Slide heater
US7550298B2 (en) 1998-09-03 2009-06-23 Ventana Medical Systems, Inc. Automated immunohistochemical and in situ hybridization assay formulations
US7615371B2 (en) 2003-12-23 2009-11-10 Ventana Medical Systems, Inc. Method and apparatus for treating a biological sample with a liquid reagent
US7718435B1 (en) 1992-05-11 2010-05-18 Dako Denmark A/S Automated slide stainer with slide housing

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4865986A (en) * 1988-10-06 1989-09-12 Coy Corporation Temperature control apparatus
WO1989009437A1 (fr) * 1988-03-26 1989-10-05 Peter Duncan Goodearl Dean Controle de la temperature de reaction
US4950608A (en) * 1989-04-25 1990-08-21 Scinics Co., Ltd. Temperature regulating container

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989009437A1 (fr) * 1988-03-26 1989-10-05 Peter Duncan Goodearl Dean Controle de la temperature de reaction
US4865986A (en) * 1988-10-06 1989-09-12 Coy Corporation Temperature control apparatus
US4950608A (en) * 1989-04-25 1990-08-21 Scinics Co., Ltd. Temperature regulating container

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0863213A1 (fr) * 1991-07-23 1998-09-09 F. Hoffmann-La Roche Ag Equipement à cycles thermiques
US7718435B1 (en) 1992-05-11 2010-05-18 Dako Denmark A/S Automated slide stainer with slide housing
US6004512A (en) * 1995-12-08 1999-12-21 Mj Research Sample cartridge slide block
WO1997021834A1 (fr) * 1995-12-08 1997-06-19 Mj Research, Inc. Magasin pour cartouches d'echantillons en tiroirs
US8246243B2 (en) 1997-03-28 2012-08-21 Applied Biosystems, Llc Thermal cycler for PCR
WO1998043740A3 (fr) * 1997-03-28 1998-12-17 Perkin Elmer Corp Ameliorations apportees a un cycleur thermique pour pcr
US7645070B2 (en) 1997-03-28 2010-01-12 Applied Biosystems, Llc Thermal cycler for PCR
US7537377B2 (en) 1997-03-28 2009-05-26 Applied Biosystems, Llc Thermal cycler for PCR
US9776187B2 (en) 1997-03-28 2017-10-03 Applied Biosystems, Llc Thermal cycler for PCR
US7133726B1 (en) 1997-03-28 2006-11-07 Applera Corporation Thermal cycler for PCR
US9044753B2 (en) 1997-03-28 2015-06-02 Applied Biosystems, Llc Thermal cycler for PCR
US6096271A (en) * 1998-02-27 2000-08-01 Cytologix Corporation Random access slide stainer with liquid waste segregation
US6783733B2 (en) 1998-02-27 2004-08-31 Cytologix Corporation Random access slide stainer with independent slide heating regulation
US6582962B1 (en) 1998-02-27 2003-06-24 Ventana Medical Systems, Inc. Automated molecular pathology apparatus having independent slide heaters
US6541261B1 (en) 1998-02-27 2003-04-01 Cytologix Corporation Method using a slide stainer with independent slide heating regulation
US7067325B2 (en) 1998-02-27 2006-06-27 Ventana Medical Systems, Inc. Removal of embedding media from biological samples and cell conditioning on automated staining instruments
US6296809B1 (en) 1998-02-27 2001-10-02 Ventana Medical Systems, Inc. Automated molecular pathology apparatus having independent slide heaters
US7217392B2 (en) 1998-02-27 2007-05-15 Cytologix Corporation Random access slide stainer with independent slide heating regulation
US6183693B1 (en) 1998-02-27 2001-02-06 Cytologix Corporation Random access slide stainer with independent slide heating regulation
WO1999044032A1 (fr) * 1998-02-27 1999-09-02 Cytologix Corporation Appareil de coloration de lames a acces selectif avec regulation thermique individuelle des lames
US7553672B2 (en) 1998-02-27 2009-06-30 Dako Denmark A/S Random access slide stainer with independent slide heating regulation
US6855552B2 (en) 1998-09-03 2005-02-15 Ventana Medical Systems Automated immunohistochemical and in situ hybridization assay formulations
US7550298B2 (en) 1998-09-03 2009-06-23 Ventana Medical Systems, Inc. Automated immunohistochemical and in situ hybridization assay formulations
US7410753B2 (en) 1998-09-03 2008-08-12 Ventana Medical Systems, Inc. Removal of embedding media from biological samples and cell conditioning on automated staining instruments
US6855559B1 (en) 1998-09-03 2005-02-15 Ventana Medical Systems, Inc. Removal of embedding media from biological samples and cell conditioning on automated staining instruments
US6544798B1 (en) 1999-02-26 2003-04-08 Ventana Medical Systems, Inc. Removal of embedding media from biological samples and cell conditioning on automated staining instruments
DE19948641A1 (de) * 1999-10-06 2001-05-10 Imb Inst Fuer Molekulare Biote Kühleinrichtung für Mikrotiterplatten-Photometer
US7425306B1 (en) 2001-09-11 2008-09-16 Ventana Medical Systems, Inc. Slide heater
US7378055B2 (en) 2002-04-26 2008-05-27 Ventana Medical Systems, Inc. Automated molecular pathology apparatus having fixed slide platforms
US7615371B2 (en) 2003-12-23 2009-11-10 Ventana Medical Systems, Inc. Method and apparatus for treating a biological sample with a liquid reagent

Also Published As

Publication number Publication date
GB9123463D0 (en) 1991-12-18
AU2804792A (en) 1993-06-07

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