EP2784150A1 - Device for thermal convection polymerase chain reaction - Google Patents

Device for thermal convection polymerase chain reaction Download PDF

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Publication number
EP2784150A1
EP2784150A1 EP11876152.7A EP11876152A EP2784150A1 EP 2784150 A1 EP2784150 A1 EP 2784150A1 EP 11876152 A EP11876152 A EP 11876152A EP 2784150 A1 EP2784150 A1 EP 2784150A1
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EP
European Patent Office
Prior art keywords
diameter section
heat radiating
test tube
radiating base
passage
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP11876152.7A
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German (de)
French (fr)
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EP2784150A4 (en
EP2784150B1 (en
Inventor
Cheng SU
Ping Hua Teng
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Genereach Biotechnology Corp
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Genereach Biotechnology Corp
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    • 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
    • B01L7/525—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 with physical movement of samples between temperature zones
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0838—Capillaries
    • 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
    • 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
    • B01L2300/1861—Means for temperature control using radiation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
    • B01L2400/0445—Natural or forced convection
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/06—Test-tube stands; Test-tube holders
    • B01L9/065—Test-tube stands; Test-tube holders specially adapted for capillary tubes

Definitions

  • the present invention relates generally to devices for use in polymerase chain reaction (hereinafter referred to as "PCR") and more particularly, to a device for holding a test tube for insulated isothermal PCR.
  • PCR polymerase chain reaction
  • PCR polymerase chain reaction
  • the PCR process comprises three major steps including denaturation, primer annealing and extension, which require different reaction temperatures.
  • the required temperature for the denaturation step is typically in a range between 90°C and 97°C.
  • the required temperature for the primer annealing step will depend on the melting temperature of the primer used. Typically, the annealing temperature ranges from 35°C to 65°C.
  • the required temperature for the extension step is typically about 72°C.
  • the insulated isothermal PCR is based on Rayleigh- Bénard convection, which is driven by buoyancy when heating fluid layer from below, is a common physical phenomenon.
  • the insulated isothermal PCR is generally performed by immersing the bottom of a test tube which contains a mixed liquid into a hot water in such a way that the rest portion of the test tube is exposed to atmosphere at room temperature for heat dissipation.
  • the temperature of the mixed liquid will gradually decrease from the bottom of the mixed liquid having a temperature of about 97°C toward the surface of the mixed liquid having a temperature of about 35°C. Because of the temperature gradient, the heat convection is induced, such that the mixed liquid will flow through various regions having different temperatures and then undergo different reaction steps.
  • the temperature at the surface of the mixed liquid will become higher and higher due to the increment of the heating time.
  • the temperature at the surface of the mixed liquid may rise to a degree higher than the required temperature suitable for conducting the primer annealing step before the convection PCR has been performed completely.
  • the polymerase chain reaction may break, such that a desired, large amount of copies of specific nucleic acid sequences may not be obtained.
  • the present invention has been accomplished in view of the above-noted circumstances. It is the primary objective of the present invention to provide a device for insulated isothermal PCR, which can ensure that the temperature at the surface of the mixed liquid is lower than the temperature suitable for conducting the primer annealing step in the PCR process.
  • the device provided by the present invention is adapted for holding a test tube in which an insulated isothermal polymerase chain reaction is performed, which comprises a heat radiating base having a body provided with a passage for insertion of the test tube.
  • the passage has a large diameter section and a small diameter section located below the large diameter section.
  • a device 10 for insulated isothermal PCR mainly comprises a heat radiating base 20 and a tube rack 30.
  • the heat radiating base 20 includes a body 22 provided with a passage 24 for insertion of a test tube 12.
  • the passage 24 has a large diameter section 241 and a small diameter section 242 located below the large diameter section 241.
  • a middle section 123 and an upper section 122 of the test tube 12 are located inside the passage 24 of the heat radiating base 20 and the heat radiating base 20 is made of a material having a high heat transfer coefficient, such as aluminum, the heat energy of the mixed liquid of PCR will be transferred through the ambient atmosphere to the heat radiating base 20 for heat dissipation efficiently, such that during the PCR process the temperature at the surface of the mixed liquid can be maintained at a degree of about 10-55°C, which is lower than the temperature suitable for performing the primer annealing step, thereby preventing the break of PCR due to high temperature at the mixed liquid level.
  • the heat dissipation of the mixed liquid at the region corresponding to the large diameter section 241 will be lower than that at the region corresponding to the small diameter section 242. It is revealed by experiments that the configuration of the heat radiating base 20 provided by the present invention has a heat-dissipating effect helpful for conducting the insulated isothermal PCR.
  • the tube rack 30 can be further provided on the heat radiating base 20.
  • the tube rack 30 is provided with a receiving hole 32 for insertion of the test tube 12 to stably position the test tube 12, thereby preventing the outer wall surface of the test tube 12 from contacting the wall surface of the passage 24 of the heat radiating base 20 so as to avoid that the temperature of the mixed liquid drops too quickly.
  • the receiving hole 32 of the tube rack 30 may be configured, in succession order from a top thereof toward a bottom thereof, a large diameter section 321, a shoulder 322 and a small diameter section 323, in which the shoulder 322 is adapted for stopping a shoulder 121 of the test tube 12 such that the test tube 12 can be stably positioned.
  • a support seat 40 is provided below the heat radiating base 20.
  • the bottom 124 of the test tube 12 is heated by a heat source (not shown in the drawings) to keep the temperature of the mixed liquid of PCR inside the bottom 124 in a range about 90°C to 97°C.
  • the bottom end 301 of the tube rack 30 is inserted into the passage 24 of the heat radiating base 20, such that the tube rack 30 is stably mounted on the heat radiating base 20.
  • the diameter of the small diameter section 242 of the passage 24 is configured to gradually and downwardly decrease. According to many experiments and modifications, it is found that using this configuration to dissipate heat can yield a highest reaction efficiency of PCR.
  • the aforesaid experiments for PCR were conducted in seven different environmental temperatures ranging from 10°C to 40°C with a condition that the mixed liquid inside the bottom 124 of the test tube 12 was heated to 93°C to 97°C.
  • the temperature of the heat radiating base 20 measured ranges from 36°C to 53°C, and the temperature at the mixed liquid level measured ranges from 36°C to 53°C; therefore, the PCR is performed smoothly.
  • the heat radiating base 20 can be provided with a plurality of passages 24 for holding a plurality of test tubes 12 for simultaneously performing polymerase chain reactions.
  • the heat radiating base 20 can be provided with a plurality of passages 24 for holding a plurality of test tubes 12 for simultaneously performing polymerase chain reactions.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

Provided in the present invention is a device (10) for thermal convection polymerase chain reaction (PCR). The device (10) is used for bearing a heat radiating base (20) which has a body (22) and a passage (24) provided through the body (22) to be used for the insertion of the test tube (12), wherein the passage (24) has a large diameter section (241) and a small diameter section (242) positioned below the large diameter section (241). Therefore, it can be ensured that during the PCR process the surface temperature of the mixed liquid is lower than the temperature required in a primer annealing reaction.

Description

    BACKGROUND OF THE INVENTION 1. Field of the Invention
  • The present invention relates generally to devices for use in polymerase chain reaction (hereinafter referred to as "PCR") and more particularly, to a device for holding a test tube for insulated isothermal PCR.
    • 2. Description of the Related Art
  • In the field of biotechnology, polymerase chain reaction (PCR) is a well-known technology used to amplify specific nucleic acid sequences. The PCR process comprises three major steps including denaturation, primer annealing and extension, which require different reaction temperatures. The required temperature for the denaturation step is typically in a range between 90°C and 97°C. The required temperature for the primer annealing step will depend on the melting temperature of the primer used. Typically, the annealing temperature ranges from 35°C to 65°C. The required temperature for the extension step is typically about 72°C.
  • The insulated isothermal PCR is based on Rayleigh- Bénard convection, which is driven by buoyancy when heating fluid layer from below, is a common physical phenomenon. The insulated isothermal PCR is generally performed by immersing the bottom of a test tube which contains a mixed liquid into a hot water in such a way that the rest portion of the test tube is exposed to atmosphere at room temperature for heat dissipation. As a result, the temperature of the mixed liquid will gradually decrease from the bottom of the mixed liquid having a temperature of about 97°C toward the surface of the mixed liquid having a temperature of about 35°C. Because of the temperature gradient, the heat convection is induced, such that the mixed liquid will flow through various regions having different temperatures and then undergo different reaction steps.
  • In the conventional device for performing a convection PCR, because the portion of the test tube, which is exposed to the ambient air at room temperature for heat dissipation, has a low heat dissipating rate, the temperature at the surface of the mixed liquid will become higher and higher due to the increment of the heating time. As a result, the temperature at the surface of the mixed liquid may rise to a degree higher than the required temperature suitable for conducting the primer annealing step before the convection PCR has been performed completely. Under this circumstance, the polymerase chain reaction may break, such that a desired, large amount of copies of specific nucleic acid sequences may not be obtained.
    • SUMMARY OF THE INVENTION
  • The present invention has been accomplished in view of the above-noted circumstances. It is the primary objective of the present invention to provide a device for insulated isothermal PCR, which can ensure that the temperature at the surface of the mixed liquid is lower than the temperature suitable for conducting the primer annealing step in the PCR process.
  • To achieve the above-mentioned objective, the device provided by the present invention is adapted for holding a test tube in which an insulated isothermal polymerase chain reaction is performed, which comprises a heat radiating base having a body provided with a passage for insertion of the test tube. The passage has a large diameter section and a small diameter section located below the large diameter section. By means of the design of the present invention, the temperature at the surface of the mixed liquid can be kept in a degree lower than the temperature suitable for conducting the primer annealing step in the PCR process.
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • The present invention will become more fully understood from the detailed description given herein below and the accompanying drawings which are given by way of illustration only, and thus are not limitative of the present invention, and wherein:
    • FIG. 1 is a schematic drawing showing a device for insulated isothermal PCR according to a preferred embodiment of the present invention; and
    • FIG. 2 is an exploded view of the device for insulated isothermal PCR of the preferred embodiment of the present invention.
    DETAILED DESCRIPTION OF THE INVENTION
  • As shown in FIG. 1, a device 10 for insulated isothermal PCR mainly comprises a heat radiating base 20 and a tube rack 30. The heat radiating base 20 includes a body 22 provided with a passage 24 for insertion of a test tube 12. The passage 24 has a large diameter section 241 and a small diameter section 242 located below the large diameter section 241. Because a middle section 123 and an upper section 122 of the test tube 12 are located inside the passage 24 of the heat radiating base 20 and the heat radiating base 20 is made of a material having a high heat transfer coefficient, such as aluminum, the heat energy of the mixed liquid of PCR will be transferred through the ambient atmosphere to the heat radiating base 20 for heat dissipation efficiently, such that during the PCR process the temperature at the surface of the mixed liquid can be maintained at a degree of about 10-55°C, which is lower than the temperature suitable for performing the primer annealing step, thereby preventing the break of PCR due to high temperature at the mixed liquid level. In addition, the heat dissipation of the mixed liquid at the region corresponding to the large diameter section 241 will be lower than that at the region corresponding to the small diameter section 242. It is revealed by experiments that the configuration of the heat radiating base 20 provided by the present invention has a heat-dissipating effect helpful for conducting the insulated isothermal PCR.
  • In order to stably mount the test tube 12 in the heat radiating base 20, the tube rack 30 can be further provided on the heat radiating base 20. The tube rack 30 is provided with a receiving hole 32 for insertion of the test tube 12 to stably position the test tube 12, thereby preventing the outer wall surface of the test tube 12 from contacting the wall surface of the passage 24 of the heat radiating base 20 so as to avoid that the temperature of the mixed liquid drops too quickly.
  • In practice, the receiving hole 32 of the tube rack 30 may be configured, in succession order from a top thereof toward a bottom thereof, a large diameter section 321, a shoulder 322 and a small diameter section 323, in which the shoulder 322 is adapted for stopping a shoulder 121 of the test tube 12 such that the test tube 12 can be stably positioned. In addition, a support seat 40 is provided below the heat radiating base 20. The bottom 124 of the test tube 12 is heated by a heat source (not shown in the drawings) to keep the temperature of the mixed liquid of PCR inside the bottom 124 in a range about 90°C to 97°C.
  • Further, the bottom end 301 of the tube rack 30 is inserted into the passage 24 of the heat radiating base 20, such that the tube rack 30 is stably mounted on the heat radiating base 20.
  • Furthermore, in the preferred embodiment of the present invention, the diameter of the small diameter section 242 of the passage 24 is configured to gradually and downwardly decrease. According to many experiments and modifications, it is found that using this configuration to dissipate heat can yield a highest reaction efficiency of PCR. The aforesaid experiments for PCR were conducted in seven different environmental temperatures ranging from 10°C to 40°C with a condition that the mixed liquid inside the bottom 124 of the test tube 12 was heated to 93°C to 97°C. The temperature of the heat radiating base 20 measured ranges from 36°C to 53°C, and the temperature at the mixed liquid level measured ranges from 36°C to 53°C; therefore, the PCR is performed smoothly.
  • The invention being thus described, it will be obvious that the same may be varied in many ways. For example, as shown in FIG. 2, the heat radiating base 20 can be provided with a plurality of passages 24 for holding a plurality of test tubes 12 for simultaneously performing polymerase chain reactions. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.

Claims (6)

  1. A device (10) for holding a test tube (12) in which insulated isothermal polymerase chain reaction is performed, the device (10) comprising:
    a heat radiating base (20) having a body (22) provided with a passage (24) for insertion of the test tube (12), wherein the passage (24) has a large diameter section (241) and a small diameter section (242) located below the large diameter section (241).
  2. The device (10) of claim 1, further comprising a tube rack (30) mounted on the heat radiating base (20) and provided with a receiving hole (32) for insertion of the test tube (12).
  3. The device (10) of claim 2, wherein the receiving hole (32) of the tube rack (30) includes, in succession order from a top of the receiving hole (32) toward a bottom of the receiving hole (32), a large diameter section (321), a shoulder (322) for stopping a shoulder (121) of the test tube (12), and a small diameter section (323).
  4. The device (10) of claim 2, wherein the tube rack (30) has a bottom end (301) inserted into the passage (24) of the heat radiating base (20).
  5. The device (10) of claims 1 to 4, wherein the small diameter section (242) of the passage (24) of the heat radiating base (20) has a diameter gradually downwardly decreasing.
  6. The device (10) of claim 1, wherein the heat radiating base (20) is made of metal.
EP11876152.7A 2011-11-22 2011-11-22 Device for polymerase chain reaction via thermal convection Active EP2784150B1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2011/001941 WO2013075263A1 (en) 2011-11-22 2011-11-22 Device for thermal convection polymerase chain reaction

Publications (3)

Publication Number Publication Date
EP2784150A1 true EP2784150A1 (en) 2014-10-01
EP2784150A4 EP2784150A4 (en) 2015-08-12
EP2784150B1 EP2784150B1 (en) 2019-05-15

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EP11876152.7A Active EP2784150B1 (en) 2011-11-22 2011-11-22 Device for polymerase chain reaction via thermal convection

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EP (1) EP2784150B1 (en)
KR (1) KR101691466B1 (en)
CN (1) CN103649301B (en)
CA (1) CA2856345C (en)
IN (1) IN2014CN03868A (en)
WO (1) WO2013075263A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105670924A (en) * 2016-03-01 2016-06-15 上海理工大学 Natural convection PCR (Polymerase Chain Reaction) microsystem
JP2018126125A (en) * 2017-02-09 2018-08-16 クレド バイオメディカル ピーティーイー リミテッド Device for heat convection type polymerase chain reaction

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016180333A1 (en) * 2015-05-12 2016-11-17 厦门大学 Nucleic acid amplification reaction tube capable of controlling liquid circulation path
CN107964507B (en) 2016-10-18 2022-09-27 财团法人工业技术研究院 Thermal convection polymerase chain reaction device and optical detection method thereof
CN108949545A (en) * 2018-08-16 2018-12-07 上海海洋大学 A kind of novel nucleic acids isothermal amplification component
CN109401948A (en) * 2018-11-01 2019-03-01 福建省博凯科技有限公司 One-part form thermal convection PCR instrument
CN109294901A (en) * 2018-11-01 2019-02-01 福建省博凯科技有限公司 One-part form thermal convection PCR instrument and control method
CN109554295B (en) * 2019-01-21 2022-03-29 武汉理工大学 PCR amplification and disease detection device for ocean-going crew

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US20080229849A1 (en) * 2007-03-22 2008-09-25 Doebler Robert W Systems and devices for isothermal biochemical reactions and/or analysis
US20100285536A1 (en) * 2001-09-15 2010-11-11 Ahram Biosystems, Inc. Method and apparatus for amplification of nucleic acid sequences by using thermal convection
WO2011086498A2 (en) * 2010-01-12 2011-07-21 Ahram Biosystems, Inc. Two-stage thermal convection apparatus and uses thereof

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DE102004039092B4 (en) * 2004-08-11 2008-04-24 Deutsches Zentrum für Luft- und Raumfahrt e.V. Locking device for linear actuators
GB0715170D0 (en) * 2007-08-03 2007-09-12 Enigma Diagnostics Ltd Reaction vessel
US20100124779A1 (en) * 2008-11-18 2010-05-20 Roche Diagnostics Operations, Inc. Two-Step Moulded Capillary

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US5616301A (en) * 1993-09-10 1997-04-01 Hoffmann-La Roche Inc. Thermal cycler
US20100285536A1 (en) * 2001-09-15 2010-11-11 Ahram Biosystems, Inc. Method and apparatus for amplification of nucleic acid sequences by using thermal convection
US20080229849A1 (en) * 2007-03-22 2008-09-25 Doebler Robert W Systems and devices for isothermal biochemical reactions and/or analysis
WO2011086498A2 (en) * 2010-01-12 2011-07-21 Ahram Biosystems, Inc. Two-stage thermal convection apparatus and uses thereof

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105670924A (en) * 2016-03-01 2016-06-15 上海理工大学 Natural convection PCR (Polymerase Chain Reaction) microsystem
JP2018126125A (en) * 2017-02-09 2018-08-16 クレド バイオメディカル ピーティーイー リミテッド Device for heat convection type polymerase chain reaction
US10688497B2 (en) 2017-02-09 2020-06-23 Credo Diagnostics Biomedical Pte. Ltd. Apparatus for thermal convection polymerase chain reaction

Also Published As

Publication number Publication date
IN2014CN03868A (en) 2015-10-16
WO2013075263A1 (en) 2013-05-30
CA2856345A1 (en) 2013-05-30
KR101691466B1 (en) 2016-12-30
CN103649301A (en) 2014-03-19
EP2784150A4 (en) 2015-08-12
KR20140040262A (en) 2014-04-02
EP2784150B1 (en) 2019-05-15
CA2856345C (en) 2017-10-24
CN103649301B (en) 2015-03-11

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