WO1993009486A1 - Dispositif permettant de reguler la temperature d'une reaction - Google Patents
Dispositif permettant de reguler la temperature d'une reaction Download PDFInfo
- 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
Links
- 238000006243 chemical reaction Methods 0.000 title claims description 9
- 229910052751 metal Inorganic materials 0.000 claims abstract description 5
- 239000002184 metal Substances 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims description 27
- 238000001816 cooling Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 6
- 238000007834 ligase chain reaction Methods 0.000 claims description 4
- 229910052709 silver Inorganic materials 0.000 claims description 4
- 239000004332 silver Substances 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000000463 material Substances 0.000 claims 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 239000004411 aluminium Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 238000005842 biochemical reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- NRUQNUIWEUZVLI-UHFFFAOYSA-O diethanolammonium nitrate Chemical compound [O-][N+]([O-])=O.OCC[NH2+]CCO NRUQNUIWEUZVLI-UHFFFAOYSA-O 0.000 description 1
- 238000005323 electroforming Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000005476 soldering Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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.
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)
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)
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 |
-
1991
- 1991-11-05 GB GB919123463A patent/GB9123463D0/en active Pending
-
1992
- 1992-11-02 WO PCT/GB1992/001996 patent/WO1993009486A1/fr active Application Filing
- 1992-11-02 AU AU28047/92A patent/AU2804792A/en not_active Abandoned
Patent Citations (3)
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)
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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