EP2784150B1 - Vorrichtung für polymerasekettenreaktionen mit thermischer konvektion - Google Patents

Vorrichtung für polymerasekettenreaktionen mit thermischer konvektion Download PDF

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Publication number
EP2784150B1
EP2784150B1 EP11876152.7A EP11876152A EP2784150B1 EP 2784150 B1 EP2784150 B1 EP 2784150B1 EP 11876152 A EP11876152 A EP 11876152A EP 2784150 B1 EP2784150 B1 EP 2784150B1
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EP
European Patent Office
Prior art keywords
diameter section
test tube
heat radiating
radiating base
passage
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Application number
EP11876152.7A
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English (en)
French (fr)
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EP2784150A1 (de
EP2784150A4 (de
Inventor
Cheng SU
Ping Hua Teng
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Genereach Biotechnology Corp
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Genereach Biotechnology Corp
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Publication of EP2784150A4 publication Critical patent/EP2784150A4/de
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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 thermal convection 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 thermal convection PCR is based on Rayleigh-Bénard convection, which is driven by buoyancy when heating fluid layer from below, is a common physical phenomenon.
  • the thermal convection 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.
  • 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.
  • a multi-stage thermal convection apparatus such as a two-stage thermal convection is disclosed.
  • the two-stage thermal convection apparatus includes a temperature shaping element that assists a thermal convection mediated Polymerase Chain Reaction (PCR).
  • PCR Thermal convection mediated Polymerase Chain Reaction
  • US 2008/0229849 A1 discloses an isothermal reaction and analysis system including a receiver to receive sample holders, a thermal control subsystem to control a temperature of the receiver, an excitation subsystem, a detection subsystem and an analysis subsystem.
  • US 5,616,301 A discloses an apparatus for automatic performance of temperature cycles in a number of test tubes in which each test tube is closed by a closure and contains a predetermined volume of a liquid reaction mixture.
  • the apparatus includes a holder, a computer-controlled automatic control system, and a device for cyclic alteration of the holder temperature.
  • 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 thermal convection 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 for a thermal convection polymerase chain reaction, comprises a test tube, a heat radiating base having a body provided with a passage for insertion of the test tube, and a tube rack mounted to the heat radiating base which has a receiving hole for insertion of the test tube thereby preventing the outer wall surface of the test tube from contacting the wall surface of the passage of the hear radiating base.
  • the passage of the body has a large diameter section and a small diameter section located below the large diameter section.
  • the large diameter section and the small diameter section of the passage respectively correspond to an upper section and a middle section of the test tube.
  • the heat radiating base is made of metal.
  • the region corresponding to the large diameter section is suitable for providing lower heat dissipation for a mixed liquid in the test tube than the region corresponding to small diameter section.
  • 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.
  • a device 10 for thermal convection 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 thermal convection 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.

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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)

Claims (4)

  1. Eine Vorrichtung (10) für eine Polymerase-Kettenreaktion mit thermischer Konvektion, aufweisend ein Reagenzglas (12), eine Wärmeabstrahl-Basis (20), die einen Körper (22) aufweist, der mit einem Durchgang (24) zum Einsetzen des Reagenzglases (12) versehen ist, und ein Reagenzglasgestell (30), das an der Wärmeabstrahl-Basis (20) montiert ist, wobei das Reagenzglasgestell ein Aufnahmeloch (32) zum Einsetzen des Reagenzglases (12) aufweist, wodurch verhindert wird, dass die Außenwandfläche des Reagenzglases (12) die Wandfläche des Durchgangs (24) der Wärmeabstrahl-Basis (20) kontaktiert, wobei der Durchgang (24) des Körpers (22) einen Abschnitt mit großem Durchmesser (241) und einen Abschnitt mit kleinem Durchmesser (242) aufweist, der unter dem Abschnitt mit großem Durchmesser (241) angeordnet ist, dadurch gekennzeichnet, dass:
    der Abschnitt mit großem Durchmesser (241) und der Abschnitt mit kleinem Durchmesser (242) des Durchgangs (24) jeweils einem oberen Abschnitt (122) und einem mittleren Abschnitt (123) des Reagenzglases (12) entsprechen, wobei die Wärmeabstrahl-Basis (20) aus Metall hergestellt ist,
    wobei der Bereich, der dem Abschnitt mit großem Durchmesser (241) entspricht, zum Bereitstellen einer geringeren Wärmeableitung für eine Mischflüssigkeit in dem Reagenzglas (12) als der Bereich, der dem Abschnitt mit kleinem Durchmesser (242) entspricht, geeignet ist.
  2. Die Vorrichtung (10) gemäß Anspruch 1, wobei das Reagenzglasgestell ein unteres Ende (301) aufweist, das in den Durchgang (24) der Wärmeabstrahl-Basis (20) eingesetzt ist.
  3. Die Vorrichtung (10) gemäß Anspruch 1, wobei das Aufnahmeloch (32) des Reagenzglasgestells (30) nacheinander von einer Oberseite des Aufnahmelochs (32) in Richtung zu einer Unterseite des Aufnahmelochs (32) einen Abschnitt mit großem Durchmesser (321), einen Ansatz (322) zum Stoppen eines Ansatzes (121) des Reagenzglases (12) und einen Abschnitt mit kleinem Durchmesser (323) aufweist.
  4. Die Vorrichtung (10) gemäß irgendeinem der vorhergehenden Ansprüche, wobei der Abschnitt mit kleinem Durchmesser (242) des Durchgangs (24) der Wärmeabstrahl-Basis (20) einen Durchmesser hat, der nach unten allmählich kleiner wird.
EP11876152.7A 2011-11-22 2011-11-22 Vorrichtung für polymerasekettenreaktionen mit thermischer konvektion Active EP2784150B1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2011/001941 WO2013075263A1 (zh) 2011-11-22 2011-11-22 热对流聚合酶连锁反应装置

Publications (3)

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

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EP11876152.7A Active EP2784150B1 (de) 2011-11-22 2011-11-22 Vorrichtung für polymerasekettenreaktionen mit thermischer konvektion

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

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KR102389800B1 (ko) * 2015-05-12 2022-04-22 시아먼 유니버시티 액체 순환 경로를 조절할 수 있는 핵산 증폭 반응 튜브
CN105670924A (zh) * 2016-03-01 2016-06-15 上海理工大学 自然对流聚合酶链反应微系统
CN107964507B (zh) 2016-10-18 2022-09-27 财团法人工业技术研究院 热对流聚合酶连锁反应装置及其光学检测方法
CN108410688A (zh) 2017-02-09 2018-08-17 克雷多生物医学私人有限公司 一种热对流式聚合酶链式反应的装置
CN108949545A (zh) * 2018-08-16 2018-12-07 上海海洋大学 一种新型核酸等温扩增反应组件
CN109401948A (zh) * 2018-11-01 2019-03-01 福建省博凯科技有限公司 一段式热对流pcr仪
CN109294901A (zh) * 2018-11-01 2019-02-01 福建省博凯科技有限公司 一段式热对流pcr仪及控制方法
CN109554295B (zh) * 2019-01-21 2022-03-29 武汉理工大学 远洋船员的pcr扩增与疾病检测装置

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KR100488281B1 (ko) * 2001-09-15 2005-05-10 아람 바이오시스템 주식회사 열 대류를 이용한 염기서열 증폭 방법 및 장치
DE102004039092B4 (de) 2004-08-11 2008-04-24 Deutsches Zentrum für Luft- und Raumfahrt e.V. Verriegelungsvorrichtung für Linearaktuatoren
WO2008116186A1 (en) * 2007-03-22 2008-09-25 Keck Graduate Institute Systems and devices for isothermal biochemical reactions and/or analysis
GB0715170D0 (en) 2007-08-03 2007-09-12 Enigma Diagnostics Ltd Reaction vessel
CA2685854A1 (en) * 2008-11-18 2010-05-18 F.Hoffmann-La Roche Ag Capillary
WO2011086498A2 (en) * 2010-01-12 2011-07-21 Ahram Biosystems, Inc. Two-stage thermal convection apparatus and uses thereof

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Also Published As

Publication number Publication date
WO2013075263A1 (zh) 2013-05-30
KR101691466B1 (ko) 2016-12-30
KR20140040262A (ko) 2014-04-02
CN103649301A (zh) 2014-03-19
CN103649301B (zh) 2015-03-11
EP2784150A1 (de) 2014-10-01
CA2856345A1 (en) 2013-05-30
EP2784150A4 (de) 2015-08-12
IN2014CN03868A (de) 2015-10-16
CA2856345C (en) 2017-10-24

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