EP2338594A1 - Plaque thermique - Google Patents

Plaque thermique Download PDF

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Publication number
EP2338594A1
EP2338594A1 EP09180560A EP09180560A EP2338594A1 EP 2338594 A1 EP2338594 A1 EP 2338594A1 EP 09180560 A EP09180560 A EP 09180560A EP 09180560 A EP09180560 A EP 09180560A EP 2338594 A1 EP2338594 A1 EP 2338594A1
Authority
EP
European Patent Office
Prior art keywords
receptacles
thermal
plate according
thermal plate
previous
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.)
Withdrawn
Application number
EP09180560A
Other languages
German (de)
English (en)
Inventor
Thomas Clemens
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.)
PEQLAB Biotechnologie GmbH
Original Assignee
PEQLAB Biotechnologie GmbH
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 PEQLAB Biotechnologie GmbH filed Critical PEQLAB Biotechnologie GmbH
Priority to EP09180560A priority Critical patent/EP2338594A1/fr
Publication of EP2338594A1 publication Critical patent/EP2338594A1/fr
Withdrawn legal-status Critical Current

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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
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/147—Employing temperature sensors
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • 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
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • 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
    • B01L2300/1894—Cooling means; Cryo cooling

Definitions

  • the present invention is directed to a thermal plate for heating and/or cooling several caps.
  • the thermal plate according to the present invention may in particular be utilized in an apparatus for performing PCR analysis.
  • PCR polymerase chain reaction
  • the thermal cycler heats and cools the reaction tubes or caps to achieve the temperatures required at each step of the reaction.
  • a PCR usually consists of a series of 20-40 repeated temperature changes called cycles (each of which typically consists of 2-3 discrete temperature steps).
  • the thermal cycler typically has a thermal block with holes where tubes or caps holding the PCR reaction mixtures can be inserted.
  • the thermal cycler then raises and lowers the temperature of the block in discrete, pre-programmed steps.
  • the temperature is typically controlled by use of peltier elements.
  • Some thermal cyclers contain silver blocks to achieve fast temperature changes and uniform temperature throughout the block.
  • Some thermal cyclers are equipped with multiple blocks along several different PCR reactions to be carried out simultaneously. It is furthermore known to provide a temperature gradient function, which allows different temperatures in different parts of the block.
  • the thermal block or thermal plate of such a thermal cycler comprises a plate made of a thermally conducting material, one or more heating and/or cooling elements arranged at the bottom side of the plate, whose purpose it is to heat and/or cool several tubes or caps arranged in reservoirs or receptacles on the top side of said plate. Furthermore, one or more temperature sensors are provided and thermally coupled to the plate of the thermal block or plate in order to allow for the calculation or estimation of the temperature in the tubes or caps.
  • WO 2008/002991 A2 relates to a low-mass sample block.
  • This application describes to reduce the mass of a the sample block by a series of hollows in the block arranged around sample wells for accommodation of samples.
  • the hollows form parallel non-intersecting channels that run parallel to the top and bottom surfaces of the sample block, while in other embodiments, the hollows form a network of intersecting passages.
  • the sample block is of unitary construction, i.e. the block is formed as a single piece by machining or molding.
  • the present invention provides a thermal plate for heating and/or cooling several tubes or caps.
  • the thermal plate comprises a base plate of thermally conducting material, several receptacles for tubes or caps being in thermal contact with the base plate, a separate support structure for supporting the receptacles being in thermal contact with the base plate and means for heating and/or cooling the base plate, wherein the support structure together with the base plate provides a substantially closed hollow space surrounding the receptacles.
  • the receptacles are adapted to receive tubes or caps in such a manner that the tubes or caps are in thermal contact with the base plate.
  • the present invention is based on the idea to replace the solid thermal block known from the prior art by a honeycomb-like or porous structure, which effectively reduces the thermal mass.
  • the thermal plate according to the present invention may much faster adapt to or reach the temperature steps of the typical PCR cycles.
  • the heat capacity of the thermal plate according to the present invention is reduced compared to the prior art, the thermal conductivity is nevertheless large enough to provide for fast temperature cycles.
  • the present invention aims at a single, substantially closed hollow space surrounding the receptacles. This hollow space allows for a good heat transfer throughout the structure, e.g. by convection or a directed fluid stream through the hollow space.
  • the thermal plate according to the present invention comprises a base plate, several receptacles and a separate support structure.
  • the sample block known from WO 2008/002991 A2 is of unitary construction. While a unitary construction is disadvantageous as outlined above, the thermal plate of the present invention can be easily and cost-effectively manufactured by mounting the single components. E.g., the receptacles may be brazed or soldered to the support structure.
  • the support structure being a separate piece allows the use of different materials for, e.g., receptacles and support structure. Thus, an optimum but more costly material may be used for the receptacles.
  • the thickness of the walls of the receptacles along their circumference is substantially constant. This allows for a homogeneous heat transfer to the samples placed in the receptacles.
  • the thickness of the wall of each sample well varies along its circumference, i.e. the thickness of the walls of the receptacles is not concentrically constant. This can be rather problematic, since this causes a difference in heat transfer from the hollows to the sample depending on the wall thickness. If the thickness of the walls of the receptacles along their circumference is substantially constant, homogenous constant heat transfer from the substantially closed hollow space to the samples in the receptacles is improved tremendously.
  • the thickness of the walls of the receptacles is in general (i.e. along their circumference and their height) substantially constant.
  • the thickness of the walls of the receptacles is between about 0,2 mm and about 1,0 mm, more preferably between about 0,3 mm and about 0,5 mm. It is preferred that the thickness of the walls of the receptacles varies less than about 20%, preferably less than about 10%.
  • the support structure for supporting the receptacles comprises vent holes. These vent holes are arranged at specific positions only in order to provide for a predetermined fluid stream.
  • a fluid stream may be utilized to additionally heat and/or cool the thermal plate.
  • the vent holes are only arranged at the top surface of the thermal plate.
  • the thermal plate comprises a fan.
  • the support structure comprises an inlet and an outlet for a cooling and/or heating fluid.
  • the fluid may be ambient air or another gas, water, oil or another fluid which is suitable for cooling and/or heating.
  • the thermal plate further comprises means for pumping the cooling fluid through the support structure.
  • the support structure accommodates one or more temperature sensors.
  • the one or more temperature sensors should be in thermal contact with the receptacles for the tubes or caps, either in direct contact or in indirect contact via, e.g., the base plate.
  • the one or more temperature sensors are located close to or adjacent the receptacles for the tubes or caps. It is in particular preferred that the temperature sensors are arranged within the substantially closed hollow space. Thus, a more precise temperature measurement my be performed. This is a further advantage of the structure according to the present invention, since the substantially closed hollow space provides enough space for such sensors on the one hand and is in thermal equilibrium with the samples on the other hand.
  • the support structure accommodates one or more optical sensors for analyzing light originating from the receptacles.
  • the support structure accommodates one or more light sources.
  • the term "light source” in the context of the present application is to be understood as any source of electromagnetic radiation including inter alia UV-light, infrared light and light from the optically visible spectrum.
  • the one or more optical sensors and the one or more light sources are preferably arranged in such a manner that light emitted from the light sources is directed into the receptacles for the tubes or caps, i.e.
  • the receptacles are optically transparent and/or comprise optically transparent windows with respect to the light emitted by the light sources. If optically transparent windows are provided, the receptacle may comprise only one window (reflective mode) or two or more windows (for measuring transmission and/or scattered light).
  • the support structure and the receptacles have a thermal conductivity of at least 0.02 W/K per receptacle, preferably of at least 0.2 W/K per receptacle.
  • the base plate and/or the support structure is made of one or a combination of the following materials : Cu, Al, Ag, Sn, Fe, C, Ceramics.
  • the receptacles have a volume between 50 ⁇ l and 300 ⁇ l, more preferably between 100 ⁇ l and 250 ⁇ l.
  • the heat capacity of the thermal plate divided by the number of receptacles is smaller than 1.6 J/K, more preferably smaller than 1.2 J/K.
  • an apparatus performing PCR analysis comprising a thermal plate as described above.
  • FIG. 1 shows a cross-section of a preferred embodiment of the thermal plate according to the present invention.
  • the thermal plate comprises a base plate 1 of thermally conducting material, several receptacles 2 for tubes or caps and a support structure 3 for supporting the receptacles. Both the receptacles and the support structure are in thermal contact with the base plate. Furthermore, means for heating and/or cooling the base plate are provided, which are not shown in Figure 1 .
  • the means for heating and/or cooling the base plate comprises one or more peltier elements.
  • the support structure 3 together with the base plate 1 provide a substantially closed hollow space surrounding the receptacles 2.
  • the receptacles are adapted to receive tubes or caps, which preferably accurately fit into the receptacles. Thus, good heat transfer from the receptacles to the tubes or caps can be guaranteed.
  • the thermal plate is made out of several separate components which are mounted together.
  • the single components may be cut, bent, and deep drawn and, e.g., soldered together.
  • a preferred material may be chosen.
  • the receptacles are specifically meant to transfer heat from and to the sample. Accordingly, the receptacles are preferably made from a material having excellent heat transfer properties, such as silver, copper or aluminium.
  • FIG. 3 shows another preferred embodiment of the thermal plate according to the present invention in a perspective sectional view.
  • This embodiment also comprises a base plate 1 of thermally connecting material, several receptacles 2 for caps being in thermal contact with the base plate and support structure 3 for supporting the receptacles 2.
  • the substantially closed hollow space surrounding the receptacles provided by the support structure 3 and the base plate 1 is more clearly visible.
  • the embodiment shown in Figure 3 additionally comprises several vent holes 3 a
  • the support structure and the base plate of said embodiment are considered to provide a substantially closed hollow space surrounding the receptacles.
  • the purpose of the vent holes 3a is to provide a stream of cooling fluid (indicated by the arrows) which promotes a fast cooling rate.
  • a fan is provided (not shown in Figure 3 ) which increases the velocity of the fluid flow through the support structure during cooling phases.
  • Figure 2a shows a perspective view of the receptacle 2 for a tube or cap having an opening 2a for inserting the tube or cap therethrough.
  • the receptacle 2 is provided with a sensor 4 which is in direct contact with the receptacle 2.
  • the sensor may be a temperature sensor, an optical sensor or another sensor for measuring parameters which are of interest when performing a PCR.
  • Figure 2b shows a perspective view of another receptacle 2 with a light source 5a and an optical sensor 5b.
  • the light source 5a may be adapted to emit electromagnetic radiation such as UV-light, infrared light or light in the visible spectrum.
  • the light source 5a may, e.g., comprise a laser diode.
  • the light emitted from the light source 5a is transmitted through the receptacle 2 and received by an optical sensor or detector 5b. While in this arrangement transmitted light is detected by the detector 5b, other arrangements of the light source 5a and the detector 5b are also possible.
  • the detector 5b may be located at a position to detect light scattered from the sample in the tube or cap received by the receptacle 2 in a certain angle.
  • the light source 5a and the light detector 5b may be arranged on the same side of the receptacle such as to measure reflected light. It should be evident that once a tube or cap comprising a sample is located within the receptacle 2, the light emitted from the light source 5a is directed into the sample.
  • the receptacles 2 are optically transparent in the light spectrum of the light source 5a or that the receptacles 2 comprise one or more optically transparent windows.
  • a receptacle 2 may have a temperature sensor 4, a light source 5a and an optical detector 5b.
  • every receptacle is provided with a light source 5a and a detector 5b, while only some of the receptacles 2 are provided with a temperature sensor 4.
  • every receptacle is provided with an optical detector 5b, while the light for all or some of the receptacles 2 is emitted from one and the same light source and directed into the samples by means of a light guide.
  • the thermal plate according to the present invention provides several advantages in view of the prior art.
  • the different components of the thermal plate according to the present invention may be simply and cost efficient manufactured.
  • the single components may be cut, bent, and deep drawn and, e.g., soldered together.
  • the substantially closed hollow space surrounding the receptacles may be easily cooled and/or heated by means of a cooling and/or heating fluid.
  • the thermal plate according to the present invention provides a large thermal conductivity while having at the same time a small heat capacity. This also decreases the time between different temperature cycles.

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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)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Optical Measuring Cells (AREA)
EP09180560A 2009-12-23 2009-12-23 Plaque thermique Withdrawn EP2338594A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09180560A EP2338594A1 (fr) 2009-12-23 2009-12-23 Plaque thermique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP09180560A EP2338594A1 (fr) 2009-12-23 2009-12-23 Plaque thermique

Publications (1)

Publication Number Publication Date
EP2338594A1 true EP2338594A1 (fr) 2011-06-29

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EP09180560A Withdrawn EP2338594A1 (fr) 2009-12-23 2009-12-23 Plaque thermique

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EP (1) EP2338594A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3126052A1 (fr) * 2014-04-04 2017-02-08 IT-IS International Ltd Système de réaction biochimique

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989009437A1 (fr) * 1988-03-26 1989-10-05 Peter Duncan Goodearl Dean Controle de la temperature de reaction
US5410130A (en) * 1994-04-20 1995-04-25 Ericomp, Inc. Heating and temperature cycling
US5710381A (en) * 1990-11-29 1998-01-20 The Perkin-Elmer Corporation Two piece holder for PCR sample tubes
WO1998043740A2 (fr) * 1997-03-28 1998-10-08 The Perkin-Elmer Corporation Ameliorations apportees a un cycleur thermique pour pcr
US20010051112A1 (en) * 2000-06-08 2001-12-13 Nico Gulzow Microtitation plate
WO2008002991A2 (fr) 2006-06-29 2008-01-03 Bio-Rad Laboratories, Inc. bloc à ÉchantillonS de masse réduite qui répond rapidement aux modifications de température
WO2008035074A2 (fr) * 2006-09-19 2008-03-27 Bg Research Ltd. Améliorations à un appareil de réaction
GB2446303A (en) * 2007-02-02 2008-08-06 Advanced Biotech Ltd Integral plastics multi-well plate

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989009437A1 (fr) * 1988-03-26 1989-10-05 Peter Duncan Goodearl Dean Controle de la temperature de reaction
US5710381A (en) * 1990-11-29 1998-01-20 The Perkin-Elmer Corporation Two piece holder for PCR sample tubes
US5410130A (en) * 1994-04-20 1995-04-25 Ericomp, Inc. Heating and temperature cycling
WO1998043740A2 (fr) * 1997-03-28 1998-10-08 The Perkin-Elmer Corporation Ameliorations apportees a un cycleur thermique pour pcr
US20010051112A1 (en) * 2000-06-08 2001-12-13 Nico Gulzow Microtitation plate
WO2008002991A2 (fr) 2006-06-29 2008-01-03 Bio-Rad Laboratories, Inc. bloc à ÉchantillonS de masse réduite qui répond rapidement aux modifications de température
WO2008035074A2 (fr) * 2006-09-19 2008-03-27 Bg Research Ltd. Améliorations à un appareil de réaction
GB2446303A (en) * 2007-02-02 2008-08-06 Advanced Biotech Ltd Integral plastics multi-well plate

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3126052A1 (fr) * 2014-04-04 2017-02-08 IT-IS International Ltd Système de réaction biochimique
US10919042B2 (en) 2014-04-04 2021-02-16 It-Is International Limited Biochemical reaction system
EP3126052B1 (fr) * 2014-04-04 2022-02-16 IT-IS International Ltd Système de réaction biochimique

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