EP3386637A1 - Temperature-control device having a reaction vessel - Google Patents
Temperature-control device having a reaction vesselInfo
- Publication number
- EP3386637A1 EP3386637A1 EP16816179.2A EP16816179A EP3386637A1 EP 3386637 A1 EP3386637 A1 EP 3386637A1 EP 16816179 A EP16816179 A EP 16816179A EP 3386637 A1 EP3386637 A1 EP 3386637A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- radiator
- reaction vessel
- lid
- cover
- hollow body
- 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
Links
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 51
- 238000010438 heat treatment Methods 0.000 claims abstract description 26
- 238000005496 tempering Methods 0.000 claims description 17
- 239000004020 conductor Substances 0.000 claims description 4
- 239000000523 sample Substances 0.000 description 34
- 239000002184 metal Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 238000011166 aliquoting Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000013013 elastic material Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F27—FURNACES; KILNS; OVENS; RETORTS
- F27B—FURNACES, KILNS, OVENS, OR RETORTS IN GENERAL; OPEN SINTERING OR LIKE APPARATUS
- F27B5/00—Muffle furnaces; Retort furnaces; Other furnaces in which the charge is held completely isolated
- F27B5/06—Details, accessories, or equipment peculiar to furnaces of these types
- F27B5/14—Arrangements of heating devices
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F27—FURNACES; KILNS; OVENS; RETORTS
- F27B—FURNACES, KILNS, OVENS, OR RETORTS IN GENERAL; OPEN SINTERING OR LIKE APPARATUS
- F27B5/00—Muffle furnaces; Retort furnaces; Other furnaces in which the charge is held completely isolated
- F27B5/06—Details, accessories, or equipment peculiar to furnaces of these types
- F27B5/18—Arrangement of controlling, monitoring, alarm or like 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
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
-
- 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
- B01L2200/02—Adapting objects or devices to another
- B01L2200/028—Modular arrangements
-
- 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
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
-
- 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
-
- 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
- B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
-
- 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
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F27—FURNACES; KILNS; OVENS; RETORTS
- F27B—FURNACES, KILNS, OVENS, OR RETORTS IN GENERAL; OPEN SINTERING OR LIKE APPARATUS
- F27B5/00—Muffle furnaces; Retort furnaces; Other furnaces in which the charge is held completely isolated
- F27B5/06—Details, accessories, or equipment peculiar to furnaces of these types
- F27B5/14—Arrangements of heating devices
- F27B2005/143—Heating rods disposed in the chamber
Definitions
- PCR polymerase chain reaction
- the nucleic acids are amplified by incubating them in a special reagent mix at defined temperatures until a finished PCR product is obtained.
- thermocyclers which normally incubate a larger number of samples in each case (eg 24, 48 or 96) in each case in a reaction vessel consisting of a closed-end tube and a cap.
- the caps are removed from the reaction vessels and then the PCR product is taken up with a pipette and transferred.
- the reaction vessels can alternatively also be closed with films and the reagent mixture can be covered with overlay media (oil, liquid wax, chill-out wax, etc.).
- overlay media oil, liquid wax, chill-out wax, etc.
- the films and optionally the overlay media are pierced with a pipette tip, a cannula or the like.
- a buffer can be admixed in this way. Often, after pipetting up, the resulting mix is heated again.
- reaction vessels are removed from the thermocycler and used again in the thermal cycler, if necessary, a further heating.
- the lid of the sample container can actually be heated to a same temperature as the sample in the sample container, it requires a lot of effort of the insulation in order to avoid any heat loss on the way to the lid. Practically, the temperature of the lid will always be at least slightly below the temperature of the metal block, so that condensation is not 100% avoidable. Regardless of whether the cover is heated directly or indirectly, the sample containers are positioned in the tempering device so that the heated cover is pressed directly onto the lid of the sample container in order to heat it to a corresponding temperature via heat conduction.
- thermo-cycle device for performing the PCR
- samples which are each arranged in a reaction vessel together in a sample block heated differently become.
- a peripheral heater around the sample block.
- the perimeter heater is not connected to the sample block. It should only warm the air in the immediate vicinity as possible to the temperature of the sample block.
- the device has a heated lid. With the heated lid pressure is exerted on the caps of the reaction vessels, so that the reaction vessels remain sealed on the one hand and on the other have good thermal contact with the sample block, through which the bottom of the reaction vessel and thus the sample is heated.
- the heating plate integrated in the lid is controlled so that it always reaches a temperature above the sample temperature, to ensure that the sample does not condense on the cap of the reaction vessel.
- the heating plate has recesses in which, where appropriate, bulges of the caps can be positioned, on which no direct pressure is exerted in order to avoid their deformation. With such a design of the caps, these can also be assigned an optical function in addition to the function of closing the reagent vessel, so that a finished PCR product without the Cap is removed or replaced, an optical reader can be supplied and the sample is optically accessible through the respective recess.
- EP 0 706 649 B1 discloses a temperature control device with which the course of the nucleic acid amplification can be monitored optically.
- a temperature control device includes a reaction chamber consisting of a closed-end tube in which the optically traced reaction mixture is located, and a cap. To avoid the condensation of the reaction mixture on walls of the reaction chamber, which are in the optical path of the device, these walls are heated.
- the cap represents the part of the wall which lies in the optical path. It is heated indirectly via a thermally conductive board (printed circuit board) with a heating element, without the board or the heating element limits the optical path.
- thermocycler for removal or insertion of the reaction vessel after or before pipetting up or down further increases the disproportion, since after each opening and closing of the thermocycler, a disproportionately large volume of space must be restored to a defined temperature ,
- a temperature control device for a symmetrical chemical reaction chamber with an internal volume for receiving a sample which has a closable inlet.
- the Reaction chamber is seated in a carrier housing with a thin, elastic material wall having heating elements that deliver heat to the peripheral surface of the reaction chamber.
- the document G 92 05 824 U1 discloses a metal block thermostat, with a metal block in which a plurality of sample vessels can be used and a detachable from the metal block cover.
- the cover can be heated independently of the metal block or be heated by thermal contact with the metal block.
- the object is achieved for a tempering device with a reaction vessel, with a thermally insulated, covered by a lid interior, in which the reaction vessel is accommodated, the reaction vessel consists of a symmetrical to an axis of symmetry, closed with a bottom hollow body and a cap solved.
- a heated heating block In the interior of a heated heating block is available. It has an inner surface which is adapted to and in contact with the bottom of the reaction vessel to heat a sample in the reaction vessel.
- the cover is made of a thermally conductive material, is covered by a heat-insulating cover and rests against the cap. The thermal conductivity of the heat-insulating cover is necessarily lower than that of the heat-conducting material of the lid.
- a heatable radiator is present, which surrounds the hollow body and at the Shape is adapted.
- the radiator communicates with the lid via a heat-conducting contact area, so that the radiator heats the hollow body directly and the cap indirectly via the lid.
- the lid has a hole through which a cannula can be inserted through the cap into the hollow body.
- the contact area is formed by a cone-shaped radiator outer surface formed on the radiator and a cone-shaped lid outer surface formed on the cover.
- the radiator outer surface is located on the inside, that is to say facing the hollow body.
- the radiator is formed at least from two radiator shells arranged symmetrically to the symmetry axis and the radiator shells are mounted in the interior via at least one spring element, so that the radiator shells are applied to the hollow body with a restoring force of the at least one spring element.
- the radiator shells are held together by at least one elastic ring.
- the lid is formed from two cover shells, which are resiliently mounted to each other.
- Fig. 1 a a tempering in longitudinal section
- Fig. 1 b is a tempering according to Fig. 1 a in cross section.
- Each tempering device according to the invention shown by way of example in FIGS. 1 a and 1 b, is specially designed for a reaction vessel 1, that is, it is individually adapted to the geometric shape and dimension of the reaction vessel 1, which is why it is not universally associated with a Reaction vessel of any geometric Shape and dimension is usable. Accordingly, the features of the temperature control can be described only in conjunction with a reaction vessel 1.
- the reaction vessel 1 consists of a to a symmetry axis 1 .0 symmetrical, with a bottom 1 .2 on one side closed hollow body 1 .1 and a cap 1 .3.
- the tempering is not limited to the application for the PCR and under a sample 8 cell suspensions, reagent mixtures, z. B. consisting of reactants and catalysts, as well as finished PCR products, present in liquid form, to be understood.
- the tempering device has a thermally insulated, closed by a cover 3 interior 2, in which a heatable heating block 7 is present, which has an inner surface 7.1, which is adapted to the bottom 1 .2 of the reaction vessel 1.
- the reaction vessel 1 is arranged standing on the heating block 7 such that its bottom 1 .2 is in contact with the inner surface 7.1 in order to heat a sample 8 located in the reaction vessel 1.
- the cover 3 is made of a thermally conductive material, is covered by a heat-insulating cover 9 and abuts the cap 1 .3.
- the hollow body 1 .1 enclosing, adapted to the form of heated radiator 4 is present, which is in communication with the lid 3 via a heat-conducting contact area 5, so that the radiator 4 the hollow body 1 .1 directly and the cap 1 .3 indirectly heated via the lid 3.
- a tempering device which is a thermocycler in connection with the PCR
- the lid 3 since the lid 3 remains closed, the defined room climate is maintained in the temperature control.
- the cap 1 .3 advantageously has a screw cap and is filled with a septum.
- the cover 3 has a hole 3.3. Providing such a hole 3.3 in the cover 3 is possible in a straightforward manner, since the cover 3 according to the invention has no heating, but is heated by heat conduction through the radiator 4, with which it is in contact via the contact region 5 with closed temperature control. The heating of the lid 3 is thus not made by an active heating but passively via heat conduction. Since the cover 3 rests against the cap 1 .3 at least over the region of the hole 3.3, the interior 2 of the tempering device is closed despite the hole 3.3.
- the contact region 5 is formed by a radiator outer surface 4.1 formed on the radiator 4 and a cover outer surface 3.1 formed on the cover 3.
- the radiator outer surface 4.1 and the outer lid surface 3.1 are arranged annularly and in a radial plane to the symmetry axis 1 .0.
- the radiator outer surface 4.1 and the outer lid surface 3.1 can be cone-shaped. The larger the cone angle is selected, the larger becomes the contact region 5, with otherwise identical dimensions of the temperature control device.
- the radiator outer surface 4.1 may be disposed within the lid outer surface 3.1.
- the radiator 4 not only has the task of heating the lid 3, but also the hollow body 1 .1 of the reaction vessel 1 and thus the gas volume of the reaction vessel 1, which is necessarily located above the sample 8, heat. In this way, primarily a condensation on the inner wall of the hollow body 1 .1 is avoided. Furthermore, by changing the temperature of the pressure of the gas volume can be changed, which is often used as a so-called thermo-pneumatic effect in fluidics.
- a cannula When a cannula is inserted into the sample 8, it is forced into the cannula with the expansion of the gas volume.
- the cannula must be closed during insertion at the outer first end until the inner second end is in contact with the sample 8. If the first end is then opened, the gas volume can expand by the sample 8 rising in the cannula until a normal pressure is established in the gas volume or the sample 8 is completely absorbed.
- the radiator 4 surrounding the hollow body 1 .1 thus not only enables the use of a passively heated cover 3 but also a quasi-passive removal of the sample 8.
- the radiator 4 may be a tubular body or advantageously consist of at least two radiator shells 4.2 arranged symmetrically to the symmetry axis 1 .0, wherein exactly two radiator shells 4.2 in the form of half shells are advantageous. While a tubular heater 4 is fixedly arranged within the interior space 2 to the axis of symmetry 1 .0, in a design of the radiator 4 as two radiator shells 4.2, the two radiator shells 4.2 to the symmetry axis 1 .0 radially elastically via at least one spring element 6 in the interior 2 and stored are held together by at least one elastic ring 1 1.
- the hollow body 1 .1 of the reaction vessel 1 is a conical shell with a small cone angle, so that with the introduction of the reaction vessel 1 in the temperature control and thus between the radiator shells 4.2 are increasingly pressed apart, with an increasingly large restoring force on the Radiator shells 4.2 acts, which ensures a nestling of the radiator shells 4.2 to the hollow body 1 .1.
- This restoring force is due to the elasticity and the spring characteristic of at least one elastic ring 1 1, for example, a rubber ring and the at least one spring element 6 influenced.
- the lid 3 can advantageously also be made of two cover shells 3.2, advantageously in the form of half shells.
- the lid outer surface 3.1 and the radiator outer surface 4.1 as shown in Fig. 1 a, cone-shaped.
- the cover shells 3.2 are then spread apart and the lid outer surfaces 3.1 pressed by restoring forces against the radiator outer surfaces 4.1.
- the restoring forces are generated by a cover shell 3.2 enclosing coil spring 10.
- the lid outer surface 3.1 is firmly positioned relative to the symmetry axis 1 .0, while the position of the radiator outer surface 4.1 radially displaces the axis of symmetry 1 .0.
- the lid outer surface 3.1 and the radiator outer surface 4.1 as annular surfaces, only the contact region 5 is thereby reduced.
Landscapes
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Mechanical Engineering (AREA)
- Biochemistry (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Devices For Use In Laboratory Experiments (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102015121362.1A DE102015121362B4 (en) | 2015-12-08 | 2015-12-08 | Temperature control device with a reaction vessel |
PCT/DE2016/100567 WO2017097289A1 (en) | 2015-12-08 | 2016-12-05 | Temperature-control device having a reaction vessel |
Publications (2)
Publication Number | Publication Date |
---|---|
EP3386637A1 true EP3386637A1 (en) | 2018-10-17 |
EP3386637B1 EP3386637B1 (en) | 2020-04-15 |
Family
ID=57590280
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP16816179.2A Active EP3386637B1 (en) | 2015-12-08 | 2016-12-05 | Temperature-control device having a reaction vessel |
Country Status (5)
Country | Link |
---|---|
US (1) | US10898901B2 (en) |
EP (1) | EP3386637B1 (en) |
CN (1) | CN108348916B (en) |
DE (1) | DE102015121362B4 (en) |
WO (1) | WO2017097289A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102423452B1 (en) * | 2017-09-19 | 2022-07-20 | 제네리치 바이오테크놀로지 코포레이션 | Heating apparatus of biochemical reaction device |
CN111939994A (en) * | 2019-05-14 | 2020-11-17 | 重庆好德译信息技术有限公司 | Heat preservation type effusion censorship test tube for endocrinology department and heat preservation method thereof |
CN112756030A (en) * | 2021-01-12 | 2021-05-07 | 许昌学院 | Heating device for calorifics is experimental |
CN116179333B (en) * | 2023-04-19 | 2023-07-04 | 鲲鹏基因(北京)科技有限责任公司 | Temperature-controlled amplification device and PCR instrument |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3764780A (en) * | 1971-06-16 | 1973-10-09 | C Ellis | Blood culture apparatus |
US6703236B2 (en) * | 1990-11-29 | 2004-03-09 | Applera Corporation | Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control |
DE9205824U1 (en) | 1992-04-30 | 1992-07-23 | Schulz, Joachim, Dipl.-Ing., O-4300 Quedlinburg, De | |
CA2130013C (en) | 1993-09-10 | 1999-03-30 | Rolf Moser | Apparatus for automatic performance of temperature cycles |
JP2909216B2 (en) | 1994-04-29 | 1999-06-23 | パーキン‐エルマー コーポレイション | Real-time detection device for nucleic acid amplification products |
CA2282623C (en) * | 1997-02-28 | 2007-05-22 | Cepheid | Heat exchanging, optically interrogated chemical reaction assembly |
EP2090366B1 (en) | 1997-03-28 | 2012-12-19 | Life Technologies Corporation | Improvements in thermal cycler for PCR |
US6558947B1 (en) * | 1997-09-26 | 2003-05-06 | Applied Chemical & Engineering Systems, Inc. | Thermal cycler |
US6730883B2 (en) * | 2002-10-02 | 2004-05-04 | Stratagene | Flexible heating cover assembly for thermal cycling of samples of biological material |
CN2634859Y (en) | 2003-07-28 | 2004-08-25 | 陈雄伟 | Temperature regulating kettle cover |
EP1745120A4 (en) * | 2004-04-16 | 2010-04-14 | Spartan Bioscience Inc | System for rapid nucleic acid amplification and detection |
US20090283512A1 (en) * | 2008-02-15 | 2009-11-19 | Eppendorf Ag | Thermal Device |
DE102010022017A1 (en) * | 2010-05-29 | 2011-12-01 | Gerstel Systemtechnik Gmbh & Co.Kg | Method for sample preparation in chromatographic separation methods and apparatus for performing a sample preparation |
US9284596B2 (en) * | 2014-02-13 | 2016-03-15 | Battelle Energy Alliance, Llc | Methods for determining enzymatic activity comprising heating and agitation of closed volumes |
-
2015
- 2015-12-08 DE DE102015121362.1A patent/DE102015121362B4/en active Active
-
2016
- 2016-12-05 EP EP16816179.2A patent/EP3386637B1/en active Active
- 2016-12-05 CN CN201680065177.7A patent/CN108348916B/en active Active
- 2016-12-05 US US16/060,528 patent/US10898901B2/en active Active
- 2016-12-05 WO PCT/DE2016/100567 patent/WO2017097289A1/en active Application Filing
Also Published As
Publication number | Publication date |
---|---|
DE102015121362A1 (en) | 2017-06-08 |
EP3386637B1 (en) | 2020-04-15 |
US20180361387A1 (en) | 2018-12-20 |
WO2017097289A1 (en) | 2017-06-15 |
DE102015121362B4 (en) | 2018-05-24 |
US10898901B2 (en) | 2021-01-26 |
CN108348916B (en) | 2021-03-09 |
CN108348916A (en) | 2018-07-31 |
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