EP2100667A1 - Système réacteur - Google Patents

Système réacteur Download PDF

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Publication number
EP2100667A1
EP2100667A1 EP08102162A EP08102162A EP2100667A1 EP 2100667 A1 EP2100667 A1 EP 2100667A1 EP 08102162 A EP08102162 A EP 08102162A EP 08102162 A EP08102162 A EP 08102162A EP 2100667 A1 EP2100667 A1 EP 2100667A1
Authority
EP
European Patent Office
Prior art keywords
insulator
reaction
reactor system
reaction chamber
thermal
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.)
Ceased
Application number
EP08102162A
Other languages
German (de)
English (en)
Inventor
designation of the inventor has not yet been filed The
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Koninklijke Philips NV
Original Assignee
Koninklijke Philips Electronics NV
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 Koninklijke Philips Electronics NV filed Critical Koninklijke Philips Electronics NV
Priority to EP08102162A priority Critical patent/EP2100667A1/fr
Priority to PCT/IB2009/050745 priority patent/WO2009107065A1/fr
Publication of EP2100667A1 publication Critical patent/EP2100667A1/fr
Ceased legal-status Critical Current

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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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • 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
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • 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
    • B01L2300/1883—Means for temperature control using thermal insulation

Definitions

  • This invention relates to a reactor system, more in particular to a reactor system for carrying out a polymerase chain reaction, still more in particular to a reactor system provided with an insulator.
  • PCR polymerase chain reaction
  • thermocyclers allow running many polymerase chain reactions (PCR) in parallel. All reactions use the identical thermo profile with the identical number of total cycles. The thermocyclers do not apply completely independent PCR thermo profiles for each one of several PCR reactions in parallel - independent in terms of number of cycles, individual temperature settings and individual time steps. This fact limits the ability to simultaneously amplify different PCR reactions that require different temperature settings for optimal performance of each individual PCR reaction.
  • US 5882903-A relates to an assay system for conducting elevated temperature reactions in a fluid-tight manner within a reaction chamber, the assay system comprising: (a) a first assembly comprising the reaction chamber, and (b) a second assembly for temperature control, wherein the second assembly can be positioned adjacent to the reaction chamber. More particularly, the invention relates to an assay system comprising (a) a reaction chamber having a cover formed of a deformable material and (b) a mechanism for rapidly adjusting the temperature of the reaction chamber.
  • Various embodiments disclosed to increase, decrease or maintain the temperature in the reaction chamber are very complicated. It requires two thermal blocks for heating or cooling the contents of the reaction chamber.
  • a reactor system for carrying out a reaction comprises at least one reaction chamber for holding reactants of the reaction; a thermal element for heating or cooling the reactants of the reaction chamber; and an insulator, wherein the insulator has a substantially high thermal resistance along a first axis as compared to the thermal resistance along a second axis.
  • the thermal resistance varies along a first axis and along a second axis
  • the thermal resistance along the first axis is higher when compared to the thermal resistance along the second axis. This high thermal resistance minimizes the heat loss to the surroundings.
  • the thermal resistance along the second axis is lower than the thermal resistance along the first axis or of the same order of magnitude as the thermal resistance within the reactor system along the same axis. This equalizes the temperature within the reactor system.
  • the lower thermal resistance along the second axis maximizes the heat transferred to cold zones of the reaction chamber and thus maintains a homogeneous temperature throughout the reaction chamber.
  • the varying thermal resistance can also be obtained by having an insulator comprising a combination of different materials with different thermal conductivities.
  • the higher thermal resistance along the first axis is achieved by a varying cross-section and/or material of the insulator.
  • the invention relates to the insulator that has a first element with a first cross section, wherein the first element is configured to make a contact with the reaction chamber, wherein the insulator has a third element with a third cross section, wherein the third element is configured to form a base of the insulator, wherein the insulator has a second element with a second cross section, and wherein the second element is configured to couple the third element to the first element.
  • An example of such an insulator with a varying cross section is a T-shaped insulator with a base. The top horizontal portion of the T-shaped insulator is in close contact with the reaction chamber and ensures a homogeneous temperature along the horizontal direction by spreading the heat uniformly. The vertical portion of the T-shaped insulator minimizes the heat losses to the surroundings.
  • the third element forms the base of the T-shaped insulator.
  • the first, second and third elements have preferably circular cross section though square, rectangular or other cross sections are not eliminated.
  • the reaction chamber is provided with a first flexible foil on a side that is making a contact with the insulator.
  • the flexible foil which forms a wall on at least one side of the reaction chamber allows manipulation of inside pressure for enabling the transportation of the reactants into and out of the reaction chamber without having any additional components.
  • the first element of the insulator is provided with a second flexible foil.
  • This flexible foil is in contact with the first flexible foil of the reaction chamber. A curvature in the first flexible foil leads to a non uniform temperature in the reaction chamber. Therefore, the insulator is placed in such a way that the second flexible foil of the insulator makes a perfect contact with the first flexible foil of the reaction chamber.
  • the insulator is provided with a through channel cutting across the three elements of the insulator.
  • the through channel is connectable to an external pressurized air and ensures good thermal contact among the reaction chamber, thermal elements and the insulator.
  • the volume of the reactants in the reaction chamber will expand and contract. In order to ensure good thermal contact with the thermal elements throughout all the cycles, this needs to be compensated by compensating the pressure on the outside of the reaction chamber.
  • the air under the second foil can be pressurized.
  • the second flexible foil of the insulator will deflect until the pressure inside the reaction chamber is same as the external pressure.
  • the invention in another embodiment, relates to a through channel that is configured to maintain a constant pressure irrespective of a pressure of surroundings. At high altitudes, ambient pressure is low and therefore the boiling temperature can be lower than the process temperature. Boiling could result in loss of water out of a sample thus effecting the concentration of the sample.
  • the constant pressure is at least atmospheric pressure.
  • the reaction chamber is made of a material and the material has a thermal conductivity in a range of 0.01 - 0.5 Wm -1 K -1 .
  • the insulator is made of a material and the material has a thermal conductivity in a range of 0.01 - 0.5 Wm -1 K -1 along the first axis.
  • the material may be polypropylene.
  • the reaction chambers have a surface to height ratio of at least 5.
  • the reaction chambers can have any form wherein the height of the chamber is smaller than its length. Examples of such chambers are flat chambers but the invention is also applicable to other geometries such as convex, concave or conical shape.
  • the reaction chamber should be relatively thin and it can be quantified by a ratio between height, H, and hydraulic diameter.
  • the ratio H:D h can be maximum of 1:5, preferably 1:10 or smaller.
  • the reaction is a polymerase chain reaction.
  • the reaction is a polymerase chain reaction.
  • Amplification of specific DNA fragments using polymerase chain reaction (PCR) process is widely used in many biochemical labs.
  • the polymerase chain reaction is used for in-vitro-diagnostics and allows simultaneous measurement of multiple analytes from a single patient sample.
  • the polymerase chain reaction provides optimized reproducible amplification conditions. Quick amplification allows rapid diagnostics. This reduces the turn-around time of the analytical instruments that require PCR amplification. Due to the integration and possible automation, untrained personnel can operate these instruments.
  • the PCR process can be used for diagnostics, for homeland security, for research and forensic applications.
  • a reactor system for carrying out multiple reactions at a uniform temperature comprises:
  • the invention provides a reactor system for executing several independent reactions, each with it's own thermal settings, in physically separated reaction chambers.
  • the flexible foil which forms a wall on at least one side of the central chamber and on at least one side of the reaction chamber allows manipulation of inside pressure for enabling the transportation of the reactants into and out of the reaction chambers without having any additional components.
  • the valve closes the reaction chambers and prevents backing-mixing of the reactants during the reaction.
  • the insulator with a geometry including varying cross sectional area ensures a uniform temperature in the reaction chamber.
  • a method for carrying out a reaction comprising thermal cycling uses the above-mentioned reactor systems. If the reaction carried out is a polymerase chain reaction, many thermal cycles have to be applied to the reactants. During this thermal cycling, the reactants inside the reaction chamber may expand and contract. In order to ensure a good thermal contact between the reaction chamber and the thermal element throughout all the thermal cycles, the expansion or contraction of the reactants needs to be compensated. The concept of compensation is based on the rigid, static side of the reaction chamber which is in contact with the thermal element.
  • reaction in the context of invention may refer to an interaction between elements to form a new substance, a physical change in state of a substance, an amplification reaction or a chemical reaction.
  • homogeneous temperature in the context of invention refers to a temperature where 90% of reactants are preferably within +/- 1 °C of a set temperature.
  • a reactor system 100 includes a reaction chamber 110, a thermal element 120 and an insulator 130.
  • the reaction chamber 110 is provided with a first flexible foil 112 on a side facing the insulator 130.
  • the insulator is provided with a second flexible foil 132 on a side adjacent to the reaction chamber 110.
  • the exploded view of the insulator 130 is shown in Fig.2 .
  • the insulator 130 has a varying cross section along a longitudinal axis.
  • the first element 134 has a first cross section whereas a third element 138 with a third cross section forms a base of the insulator 130.
  • the insulator has a second element 136 with a second cross section that couples the third element 138 to the first element 134.
  • the insulator is provided with a channel 140 cutting across all the three elements.
  • Fig.3 is a two dimensional view of the reactor system 100.
  • the reactor system 100 includes the reaction chamber 110, the thermal element 120 and the insulator 130.
  • the reaction chamber 110 is provided with the first flexible foil 112 on a side facing the insulator 130.
  • the insulator is provided with the second flexible foil 132 on a side adjacent to the reaction chamber 110.
  • the insulator 130 has the first 134, the second 136 and the third element 138.
  • the insulator 130 is provided with a channel 140.
  • Fig.4 shows a reactor system 200 with multiple reaction chambers of which only two reaction chambers 220 are shown.
  • the reactor system 200 is provided with a central chamber 210.
  • the central chamber 210 is provided with at least one flexible wall 212.
  • the reaction chambers 220 are provided with a flexible wall on a first side and with a rigid wall on a second side (not shown).
  • Fluidic channels 230 connect the central chamber 210 and the reaction chambers 220.
  • a valve 240 is provided for opening and closing all the fluidic channels 230 simultaneously.
  • a thermal element 250 per reaction chamber 220 is situated facing a second side of the reaction chamber 220.
  • An insulator 260 per reaction chamber 220 is situated facing the first side of each reaction chamber 220.
  • the insulator 260 is provided with a channel 265.
  • the reaction chamber 110 of Fig.1 is loaded with reactants required for carrying out a reaction.
  • the reaction chamber 110 is held between the thermal element 120 and the insulator 130.
  • the volume of the reactants inside the reaction chamber 110 will expand and contract.
  • the channel 140 of the insulator 130 is connected to an externally pressurized air. This will pressurize the air below the second flexible foil 132.
  • the second flexible foil 132 will deflect until the pressure inside the reaction chamber 110 is same as the pressurized air. This ensures that the reaction will always be performed under identical conditions irrespective of the ambient conditions. By maintaining at least the ambient pressure at sea level, boiling of the reactants is prevented.
  • the insulator 130 as shown in Fig.2 has a varying cross section along a longitudinal axis.
  • the first element 134 with a first cross section makes a contact with the reaction chamber 110.
  • the insulator 130 has a third element 138 with a third cross section which forms a base of the insulator 130.
  • the insulator has a second element 136 with a second cross section that couples the third element 138 to the first element 134.
  • the insulator is provided with a channel 140 cutting across all the three elements.
  • the cross-sectional area of the insulator is such that the thermal resistance along the first axis 152 is high enough to insulate the reaction system from the surroundings, while the thermal resistance in the second axis 154 is low enough to equalize the temperature within the reaction chamber. This ensures that the heat transferred to the surroundings is minimized whereas the heat transferred to cold parts of the reaction chamber 110 is maximized. This maintains a homogeneous temperature in the reaction chamber 110.
  • the insulator 260 is brought upwards by applying a force F until the reaction chamber 220 is clamped between the thermal element 250 and the insulator 260.
  • the thermal element 250 heats the reactants of the reaction chamber 220 to a desired temperature.
  • the insulator 260 ensures that the heat is not lost to the atmosphere. This further ensures uniform temperature throughout the reaction chamber without any hot or cold spots.
  • the central chamber 210 can be pre-filled with the reactants.
  • the valve 240 is opened and a pressure is applied on the flexible top foil 212 of the central chamber 210. As a result, the reactants are pressed into the reaction chamber 220 via the fluidic channels 230.
  • Each reaction chamber 220 has one fluidic channel 230.
  • the upward force F on the insulator 260 needs to be larger than the projected reactant volume of the reaction chamber 220multiplied by the pressure exerted by the reactants in the reaction chamber 220.
  • the valve 240 is closed after all the reaction chambers 220 are filled. Volume of the reaction chamber 220 is determined by the geometry of the reaction chamber 220.
  • the reaction takes place.
  • the force F upwards is still present. This maintains a controlled pressure on the reactants and keeps the reaction chamber 220 pressed to the thermal element 250.
  • Connecting externally pressurized air via the channel 265 in the insulator 260 can pressurize the air under the second flexible foil.
  • the air under the second flexible foil gives compliance to the reaction chamber 220 and ensures a good contact with the thermal element 250.
  • expansion of the reactants is compensated by the air buffer under the second flexible foil. If the reaction carried out is a polymerase chain reaction, many thermal cycles have to be applied to the reactants. During this thermal cycling, the reactants inside the reaction chamber 220 may expand and contract.
  • the expansion or contraction of the reactants needs to be compensated.
  • the concept of compensation is based on the rigid, static side of the reaction chamber 220 which is in contact with the thermal element 250.
  • the reaction chamber 220 is pressed upwards to the thermal element 250 by a force F. This force is exerted by a spring or pressure loaded support element (not shown). Every reaction chamber 220 has its own support element in order to ensure good thermal contact of all the individual reaction chambers 220 and the thermal element 250. Any play between them is eliminated. Since the reaction chambers 220 are closed by the first flexible foil on at least one side, expansion or contraction of the reactants can take place.
  • the supporting elements of the first flexible foil which are also flexible allow the resulting motion of the flexible foil, without losing preload of the reaction chamber 220 to the thermal element 250.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
EP08102162A 2008-02-29 2008-02-29 Système réacteur Ceased EP2100667A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP08102162A EP2100667A1 (fr) 2008-02-29 2008-02-29 Système réacteur
PCT/IB2009/050745 WO2009107065A1 (fr) 2008-02-29 2009-02-25 Système de réacteur

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP08102162A EP2100667A1 (fr) 2008-02-29 2008-02-29 Système réacteur

Publications (1)

Publication Number Publication Date
EP2100667A1 true EP2100667A1 (fr) 2009-09-16

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Family Applications (1)

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EP08102162A Ceased EP2100667A1 (fr) 2008-02-29 2008-02-29 Système réacteur

Country Status (2)

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EP (1) EP2100667A1 (fr)
WO (1) WO2009107065A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004022083A1 (fr) 2002-09-04 2004-03-18 Dsm Ip Assets B.V. Composition nutritionnelle et therapeutique d'agent sensibilisant a l'insuline et de fraction peptidique
CN103502796A (zh) * 2011-04-27 2014-01-08 皇家飞利浦有限公司 具有可更换盒体和阅读器的传感器系统

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19519015C1 (de) * 1995-05-24 1996-09-05 Inst Physikalische Hochtech Ev Miniaturisierter Mehrkammer-Thermocycler
US5882903A (en) 1996-11-01 1999-03-16 Sarnoff Corporation Assay system and method for conducting assays
US5958349A (en) * 1997-02-28 1999-09-28 Cepheid Reaction vessel for heat-exchanging chemical processes
US20020115200A1 (en) * 2001-02-16 2002-08-22 Institute Of Microelectronics Miniaturized thermal cycler
US20040043479A1 (en) * 2000-12-11 2004-03-04 Briscoe Cynthia G. Multilayerd microfluidic devices for analyte reactions
WO2007004103A1 (fr) * 2005-06-30 2007-01-11 Koninklijke Philips Electronics N.V. Cartouche pour diagnostic medical automatique

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19519015C1 (de) * 1995-05-24 1996-09-05 Inst Physikalische Hochtech Ev Miniaturisierter Mehrkammer-Thermocycler
US5882903A (en) 1996-11-01 1999-03-16 Sarnoff Corporation Assay system and method for conducting assays
US5958349A (en) * 1997-02-28 1999-09-28 Cepheid Reaction vessel for heat-exchanging chemical processes
US20040043479A1 (en) * 2000-12-11 2004-03-04 Briscoe Cynthia G. Multilayerd microfluidic devices for analyte reactions
US20020115200A1 (en) * 2001-02-16 2002-08-22 Institute Of Microelectronics Miniaturized thermal cycler
WO2007004103A1 (fr) * 2005-06-30 2007-01-11 Koninklijke Philips Electronics N.V. Cartouche pour diagnostic medical automatique

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004022083A1 (fr) 2002-09-04 2004-03-18 Dsm Ip Assets B.V. Composition nutritionnelle et therapeutique d'agent sensibilisant a l'insuline et de fraction peptidique
CN103502796A (zh) * 2011-04-27 2014-01-08 皇家飞利浦有限公司 具有可更换盒体和阅读器的传感器系统
EP2702390A1 (fr) * 2011-04-27 2014-03-05 Koninklijke Philips N.V. Système de capteur comportant une cartouche remplaçable et un lecteur
CN103502796B (zh) * 2011-04-27 2016-10-26 皇家飞利浦有限公司 具有可更换盒体和阅读器的传感器系统
US9696246B2 (en) 2011-04-27 2017-07-04 Koninklijke Phlips N.V. Sensor system with an exchangeable cartridge and a reader
EP2702390B1 (fr) * 2011-04-27 2021-05-26 Siemens Healthineers Nederland B.V. Système de capteur comportant une cartouche échangeable et un lecteur, cartouche échangeable pour un tel système de capteur et utilisation du système de capteur ou de la cartouche
EP3904860A1 (fr) * 2011-04-27 2021-11-03 Siemens Healthineers Nederland B.V. Système capteur doté d'une cartouche échangeable et d'un lecteur

Also Published As

Publication number Publication date
WO2009107065A1 (fr) 2009-09-03

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