WO2006042825A1 - Verfahren zur ventilsteuerung bei der thermozyklisierung einer substanz zwecks pcr und zugehörige anordnung - Google Patents
Verfahren zur ventilsteuerung bei der thermozyklisierung einer substanz zwecks pcr und zugehörige anordnung Download PDFInfo
- Publication number
- WO2006042825A1 WO2006042825A1 PCT/EP2005/055269 EP2005055269W WO2006042825A1 WO 2006042825 A1 WO2006042825 A1 WO 2006042825A1 EP 2005055269 W EP2005055269 W EP 2005055269W WO 2006042825 A1 WO2006042825 A1 WO 2006042825A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- valves
- pcr
- temperature
- arrangement according
- chamber
- Prior art date
Links
Classifications
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
-
- 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
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
-
- 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
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0036—Operating means specially adapted for microvalves operated by temperature variations
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0036—Operating means specially adapted for microvalves operated by temperature variations
- F16K99/0038—Operating means specially adapted for microvalves operated by temperature variations using shape memory alloys
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0042—Electric operating means therefor
- F16K99/0044—Electric operating means therefor using thermo-electric means
-
- 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
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0877—Flow chambers
-
- 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
- B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
-
- 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
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0633—Valves, specific forms thereof with moving parts
-
- 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
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0633—Valves, specific forms thereof with moving parts
- B01L2400/0661—Valves, specific forms thereof with moving parts shape memory polymer valves
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2201/00—Properties
- C08L2201/12—Shape memory
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K2099/0082—Microvalves adapted for a particular use
- F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology
Definitions
- the invention relates to a method for Ventilsteue ⁇ tion in the thermocyclization of a substance for the purpose of PCR.
- the invention relates to the associated Anord ⁇ tion for carrying out the method.
- the PCR chamber is filled via an inflow channel and emptied via a Ab ⁇ flow channel.
- the thermal cycling for the PCR temperatures between 50 and 95 0 C are set. Since ⁇ at increasing due to outgassing of the dissolved air and heat from ⁇ the water the pressure in the chamber elongation and there may be a displacement of the liquid and thus to unkontrol ⁇ profiled conditions occur during the PCR. In order to avoid this, both the inflow and outflow of the PCR chamber must be closed.
- a movable, elastic membrane or film can be applied to the respective channel, e.g. Inflow channel, to be pressed.
- a mechanical force must be used.
- valve drive systems are known from the prior art.
- the object of the invention is therefore to provide an improved procedural ren for valve control in the thermocycling PCR in a and provide an associated fen arrangement to sheep ⁇ .
- the object is achieved by the measures of Pa ⁇ tent tapees 1.
- An associated arrangement is indicated in Pa ⁇ tent contract 5. Further developments of the method and the associated device are the subject of Unteransprü- che.
- the subject matter of the invention is therefore such a valve control in the thermocyclization of a substance for the purpose of PCR, wherein the PCR chamber automatically closes by means of controllable valves.
- the thermal properties of Me ⁇ be used metals such that they communicate with the for PCR ⁇ not manoeuvrable heating / cooling actuator in direct contact.
- the thermal properties of metals are utilized in that either memorys metal elements or else bimetallic elements are used which define the closed position of the valves when hot , When falling below the predetermined temperature, however, spring elements are used, which cause the valves to open.
- the invention makes use of the technique of memory metals.
- the precisely definable switching temperature results in an optimal closing behavior, which can be used to advantage for valves for PCR chambers.
- a separate thermal Aktu- ator cost, size
- the heating and cooling elements already present for the thermal cyclization are used as actuators for the memory metal technology, their specific arrangement and their operation being essential.
- Figure 1 shows schematically the principle of the invention
- Figure 2 shows a correspondingly constructed Ventilan ⁇ order in the open and in the closed state
- Figure 4 shows the time course of a Thermozyklmaschines- curve using the valve control according to the invention.
- FIG. 1 shows a fluidic channel 1 which has cross-sectional dimensions of 10 ⁇ m to a few mm.
- the fluidic channel 1 is in thermal contact 4 with a heating / cooling actuator 6.
- a mechanical actuator 5 as a valve is also in contact with the heating / cooling actuator 6.
- the mechanical actuator is e.g. a combination of memory metal and a spring element, which is illustrated with reference to Figures 2 and 3.
- the heating / cooling actuator can set at least two temperatures Ti and T 2 .
- the mechanical actuator 5 assumes two different positions 5a and 5b, so that in the position 5a / 2a the flow in the channel 1 is made possible and in the position 5b / 2b the flow in the channel 1 is interrupted.
- FIGS. 2 and 3 show a detail of the thermo-actuator region with heating / cooling, as described in detail in particular in the applicant's parallel patent application with the same application priority.
- a cartridge (card) 100 is inserted into the actuator area in order to be able to carry out a PCR there.
- the card is a so-called cartridge 100 consisting of a planar plastic body 101 provided with structures of microchannels or microcavities, on which a foil 121 is applied.
- a recess is present as a sample chamber 120.
- Flow channels 134 and 135 serve as an inflow or outflow for the sample liquid.
- thermo coupling plate 14 Furthermore, there are a thermal coupling plate 14, a ⁇ A device with Peltier elements 16 and one unit withhari ⁇ bodies 17 indicated.
- Memory metals are known in the art. These are understood to mean those metallic materials which microscopically change their structure at a defined temperature by diffusion-free (martensitic) phase transformations. These materials are defined by alloys with specific alloying components. Are suitable in particular for ⁇ sondere copper-base or nickel-based alloys, game as criz ⁇ Cu-Zn-Al or Ni-Ti.
- the microscopic structure change in a predetermined macroscopic shape change so that such memory metals can be implemented, also commonly referred to as Formgedumblet ⁇ nis alloys are referred to.
- transition temperatures can be specified.
- form elements can be formed from memory metals which change their shape when this temperature is reached and thus in particular realize a switching function.
- the memory metal element 25 When falling below a predetermined temperature Tem ⁇ the memory metal element 25 has a position according to figure 2. It is in particular at room temperature slightly warp ⁇ bar and is held by the spring elements 26/27 in the form shown in Figure 2. The memory metal element 25 thus does not press the valve members 21 and 22, which ⁇ be indicated that both valves 22, 22 'are open and flow sample liquid in the examination chamber 33 can.
- the memory metal element 25 returns to its grammed vorpro ⁇ , rigid mold back and overcomes the spring force of the springs 26 and 27 by the pressure of the valve elements 21 and 22, the film 32 deformed and the inflow 34 and 35 of the flow channel is completed / sealed.
- the temporal temperature profile is shown in the PCR: Plotted on the abscissa is the time and on the ordinate, the temperature in the range between 2O 0 C (room temperature) and about 95 0 C (upper limit temperature of the thermocyclization).
- the PCR can now be carried out:
- the temperature is raised to about 95 0 C and periodically varied according to a predetermined program according to the graph 41 between this value and a lower temperature of about 5O 0 C with an intermediate plateau value of about 7O 0 C. It is possible to go through n cycles.
- valve arrangement described opening and closing of the sample chamber is thus possible in a simple manner, the opening taking place in each case when the temperature falls below a lower limit temperature after the PCR has been carried out. Since this valve arrangement can be integrated in a simple manner into the thermal actuator with heating and cooling, a particularly simple problem solution results for the specific application.
- valve element made of memory metal has a steep closing function, which is illustrated there by the hatched area 42.
- This narrow region 42 is particularly important for the PCR, in particular in the case of thermal coupling to the heating / cooling actuator for the PCR.
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/665,297 US9267616B2 (en) | 2004-10-15 | 2005-10-14 | Method for controlling valves during the thermocyclization of a substance for the purpose of polymer chain reaction (PCR) and associated arrangement |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102004050510A DE102004050510B4 (de) | 2004-10-15 | 2004-10-15 | Verfahren zur Ventilsteuerung bei der Thermozyklisierung einer Substanz zwecks PCR und zugehörige Anordnung |
DE102004050510.1 | 2004-10-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006042825A1 true WO2006042825A1 (de) | 2006-04-27 |
Family
ID=35511305
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2005/055269 WO2006042825A1 (de) | 2004-10-15 | 2005-10-14 | Verfahren zur ventilsteuerung bei der thermozyklisierung einer substanz zwecks pcr und zugehörige anordnung |
Country Status (3)
Country | Link |
---|---|
US (1) | US9267616B2 (de) |
DE (1) | DE102004050510B4 (de) |
WO (1) | WO2006042825A1 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102015002854A1 (de) * | 2015-03-05 | 2016-09-08 | Fidica Gmbh & Co. Kg | Probeentnahmeventil |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7851227B2 (en) * | 2004-10-15 | 2010-12-14 | Siemens Aktiengesellschaft | Method for carrying out an electrochemical measurement on a liquid measuring sample in a measuring chamber that can be accessed by lines, and corresponding arrangement |
KR101269741B1 (ko) * | 2006-07-04 | 2013-05-30 | 쓰리엠 이노베이티브 프로퍼티즈 캄파니 | 탄성 및 접착성을 갖는 전자기파 차단용 가스켓 |
WO2009098485A1 (en) * | 2008-02-07 | 2009-08-13 | Forensic Sciences Service Ltd | Improvements in and relating to analysis |
DE102009001257A1 (de) | 2008-10-06 | 2010-04-15 | Aj Ebiochip Gmbh | Vorrichtung und Verfahren zur Handhabung von Flüssigkeiten |
WO2010091406A2 (en) * | 2009-02-09 | 2010-08-12 | Forensic Science Service Limited | Improvements in and relating to devices |
KR20120020528A (ko) | 2010-08-30 | 2012-03-08 | 삼성전자주식회사 | 중합효소 연쇄반응 장치 |
GB2511566B (en) * | 2013-03-08 | 2018-09-26 | Intelligent Energy Ltd | Gas supply cartridge |
DE102018112065A1 (de) * | 2018-05-18 | 2019-11-21 | Memetis Gmbh | Ventil mit Aktuator aus einer Formgedächtnislegierung in flacher Geometrie |
CN113174327B (zh) * | 2021-01-15 | 2021-12-31 | 北京中科生仪科技有限公司 | 基于pcr扩增仓的搅动控制方法 |
CN112891986B (zh) * | 2021-01-30 | 2022-05-03 | 哈尔滨工业大学 | 一种集成封闭式核酸自动提取装置 |
Citations (3)
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US20010048895A1 (en) * | 1997-02-28 | 2001-12-06 | Jorma Virtanen | Laboratory in a disk |
EP1174182A1 (de) * | 1999-02-18 | 2002-01-23 | Toyo Kohan Co., Ltd. | Mikrochip für chemische reaktionen |
WO2004042357A2 (en) * | 2002-11-04 | 2004-05-21 | The Regents Of The University Of Michigan | Thermal micro-valves for micro-integrated devices |
Family Cites Families (10)
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US4990883A (en) * | 1989-06-09 | 1991-02-05 | Raychem Corporation | Actuator which can be locked when exposed to a high temperature |
US5325880A (en) * | 1993-04-19 | 1994-07-05 | Tini Alloy Company | Shape memory alloy film actuated microvalve |
US5529279A (en) * | 1994-08-24 | 1996-06-25 | Hewlett-Packard Company | Thermal isolation structures for microactuators |
US5585069A (en) * | 1994-11-10 | 1996-12-17 | David Sarnoff Research Center, Inc. | Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis |
US20020022261A1 (en) * | 1995-06-29 | 2002-02-21 | Anderson Rolfe C. | Miniaturized genetic analysis systems and methods |
US5856174A (en) * | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US6709869B2 (en) * | 1995-12-18 | 2004-03-23 | Tecan Trading Ag | Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system |
US20040053290A1 (en) * | 2000-01-11 | 2004-03-18 | Terbrueggen Robert Henry | Devices and methods for biochip multiplexing |
FR2817604B1 (fr) * | 2000-12-01 | 2004-04-23 | Biomerieux Sa | Vannes activees par des polymeres electro-actifs ou par des materiaux a memoire de forme, dispositif contenant de telles vannes et procede de mise en oeuvre |
CA2501857A1 (en) * | 2002-10-09 | 2004-04-22 | The Board Of Trustees Of The University Of Illinois | Microfluidic systems and components |
-
2004
- 2004-10-15 DE DE102004050510A patent/DE102004050510B4/de active Active
-
2005
- 2005-10-14 WO PCT/EP2005/055269 patent/WO2006042825A1/de active Application Filing
- 2005-10-14 US US11/665,297 patent/US9267616B2/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20010048895A1 (en) * | 1997-02-28 | 2001-12-06 | Jorma Virtanen | Laboratory in a disk |
EP1174182A1 (de) * | 1999-02-18 | 2002-01-23 | Toyo Kohan Co., Ltd. | Mikrochip für chemische reaktionen |
WO2004042357A2 (en) * | 2002-11-04 | 2004-05-21 | The Regents Of The University Of Michigan | Thermal micro-valves for micro-integrated devices |
Non-Patent Citations (1)
Title |
---|
SHOJI S ET AL: "MICROFLOW DEVICES AND SYSTEMS", JOURNAL OF MICROMECHANICS & MICROENGINEERING, NEW YORK, NY, US, vol. 4, no. 4, December 1994 (1994-12-01), pages 157 - 171, XP000863761, ISSN: 0960-1317 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102015002854A1 (de) * | 2015-03-05 | 2016-09-08 | Fidica Gmbh & Co. Kg | Probeentnahmeventil |
US9995658B2 (en) | 2015-03-05 | 2018-06-12 | Fidica Gmbh & Co. Kg | Sampling point valve |
DE102015002854B4 (de) | 2015-03-05 | 2022-12-15 | Fidica Gmbh & Co. Kg | Probeentnahmeventil |
Also Published As
Publication number | Publication date |
---|---|
DE102004050510B4 (de) | 2012-01-12 |
US20070265439A1 (en) | 2007-11-15 |
US9267616B2 (en) | 2016-02-23 |
DE102004050510A1 (de) | 2006-04-20 |
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