EP2198964A1 - Procédé destiné à la préparation d'un réactif séché dans un système microfluidique et système microfluidique - Google Patents

Procédé destiné à la préparation d'un réactif séché dans un système microfluidique et système microfluidique Download PDF

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Publication number
EP2198964A1
EP2198964A1 EP08019462A EP08019462A EP2198964A1 EP 2198964 A1 EP2198964 A1 EP 2198964A1 EP 08019462 A EP08019462 A EP 08019462A EP 08019462 A EP08019462 A EP 08019462A EP 2198964 A1 EP2198964 A1 EP 2198964A1
Authority
EP
European Patent Office
Prior art keywords
microfluidic
microfluidic structure
reagent
carrier medium
providing
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
Application number
EP08019462A
Other languages
German (de)
English (en)
Other versions
EP2198964B1 (fr
EP2198964B8 (fr
Inventor
Valerie Dr. Winckler-Desprez
Manfred Augstein
Romi Roedl
Susanne Wuerl
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.)
F Hoffmann La Roche AG
Roche Diagnostics GmbH
Original Assignee
F Hoffmann La Roche AG
Roche Diagnostics 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 F Hoffmann La Roche AG, Roche Diagnostics GmbH filed Critical F Hoffmann La Roche AG
Priority to EP08019462.4A priority Critical patent/EP2198964B8/fr
Priority to US12/573,472 priority patent/US8790932B2/en
Priority to CA2684268A priority patent/CA2684268A1/fr
Priority to JP2009254147A priority patent/JP2010112953A/ja
Priority to CN200910212006A priority patent/CN101737989A/zh
Publication of EP2198964A1 publication Critical patent/EP2198964A1/fr
Publication of EP2198964B1 publication Critical patent/EP2198964B1/fr
Application granted granted Critical
Publication of EP2198964B8 publication Critical patent/EP2198964B8/fr
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502707Containers 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 the manufacture of the container or its components
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26DRYING
    • F26BDRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B5/00Drying solid materials or objects by processes not involving the application of heat
    • F26B5/04Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
    • F26B5/06Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12Specific details about manufacturing devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16Reagents, handling or storing thereof
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2525Stabilizing or preserving
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575Volumetric liquid transfer

Definitions

  • the invention relates to a method for providing a dried reagent in a microfluidic system as well as a microfluidisclies system.
  • Microfluidic systems have, at least in sections, a microfluidic structure in which one or more microcompartments and / or microchannels are formed.
  • microfluidic systems are provided as microfluidic test elements or test systems with which one or more analytes can be analyzed, for example, in a sample of body fluid.
  • one or more reagents are then provided in the microfluidic structure, in particular for a detection reaction with the analyte to be analyzed.
  • the one or more reagents are arranged in the microchannels and / or the microcompartments of the microfluidic structure, so that they come into contact with the sample liquid when the sample to be examined is placed on the microfluidic test element, whereupon a detection reaction usually takes place.
  • Lyophilization is a freeze-drying process that results in the removal of liquid from the frozen material in vacuo. In this freezing of the solvent, which is usually water, the solvent evaporates in the frozen state (sublimation drying). In this way, a gentle drying and preservation of one or more reagents is possible.
  • the end product of lyophilization is a frozen mass (lyophilisate), which may also be referred to as a porous, stable and dry "lyo cake”.
  • the lyophilized pellets may contain various biological reagents or microparticles.
  • the pellets are prepared by placing drops of a reagent solution on a cooled plate and frozen there, followed by vacuum treatment.
  • the object of the invention is to provide a method for providing a dried reagent in a microfluidic system as well as a microfluidic system in which at least one dried reagent can be introduced into the microfluidic system for retention herein in a flexible and adaptable manner to a particular application ,
  • One aspect of the invention is a method for providing a dried reagent in a microfluidic system, the method comprising the steps of: providing a microfluidic system having a microfluidic structure, introducing a reagent-containing flowable carrier medium into the microfluidic structure, and drying of the reagent in the microfluidic structure by lyophilization.
  • a microfluidic system in which a lyophilization-dried reagent is arranged in a microfluidic structure.
  • the possibility is created to first introduce the reagent to be stored in the microfluidic structure in dissolved or suspended form into the microfluidic structure in order then to carry out a drying by means of lyophilization.
  • the reagent can be more easily introduced into the sections of the microfluidic structure by means of the flowable carrier medium, for example in the form of a solution or a suspension. It is not necessary to geometrically separate the sections of the microfluidic structure for the Incorporation of pellets or particles to optimize. Rather, the carrier medium, which may be, for example, water, flows with the reagent into the sections of the microfluidic structure in the microfluidic system.
  • microfluidic structure may in this case be formed in sections in the microfluidic system or this essentially completely.
  • the advantage is that the dried reagent dissolves rapidly and completely in a liquid.
  • the dried reagent dissolves rapidly and completely in a liquid.
  • aqueous solution which is introduced into the microfluidic structure when using the microfluidic system. This is particularly advantageous for kinetic measurements, for example.
  • one or more reagents can be incorporated into the microfluidic structure.
  • the incorporation of several reagents can also be carried out, for example, by multiple application of the steps for introducing the carrier medium and subsequent lyophilization. However, such a multiple application can also be provided in connection with the introduction of only one reagent in the microfluidic structure.
  • a preferred embodiment of the invention provides that the microfluidic structure is thermally treated prior to introduction of the flowable carrier medium. In this way, the incorporation of the reagent (s) in the microfluidic structure can be specifically influenced.
  • the microfluidic structure is thermally treated when the flowable carrier medium is introduced.
  • An advantageous embodiment of the invention provides that the microfluidic structure is cooled during the thermal treatment.
  • the cooling of the microfluidic structure is a form of thermal treatment in which, for example, the microfluidic structure or parts thereof or the entire microfluidic system are cooled.
  • the cooling can be done so far that the flowable carrier medium freezes after application on contact with the surface of the microfluidic structure equal or in temporal proximity thereto. In this way, a targeted influencing of the distribution of the flowable carrier medium within the microfluidic structure is made possible. Cooling is advantageous, for example, if the flowable carrier medium contains a surfactant whose distribution in the microfluidic structure can be influenced in a targeted manner.
  • a development of the invention provides that the microfluidic structure is heated during the thermal treatment.
  • the heating is another form of thermal treatment of the microfluidic system or parts thereof, in particular the micro fluidic structure.
  • This type of thermal treatment can also be used to control and regulate the spatial distribution of the reagent suspension or solution within the microfluidic structure.
  • heating is advantageous when the flowable carrier medium contains surfactants whose distribution is otherwise difficult to control in microfluidic structures.
  • An expedient embodiment of the invention may provide that the reagent is incorporated in the microfluidic structure with a substantially homogeneous distribution.
  • the flowable carrier medium contains one or more surfactants and / or one or more fillers. These form after drying a kind of chemical lattice for the one or more reagents in the microfluidic structure, whereby, for example, a homogeneous and rapid dissolution of the reagents is supported.
  • microfluidic test element selected from the following group of systems: microfluidic test element and microfluidic chip.
  • test elements are preferably used, as they are as such in the document EP 1 916 524 A1 are described.
  • analysis systems that are loaded with dry reagents and are substantially disk-shaped.
  • a reagent solution or suspension is initially prepared in which one or more reagents are present in dissolved or suspended form.
  • the microfluidic system is then provided, for example in the form of a microfluidic test element or a microfluidic chip.
  • the reagent solution or suspension is applied, for example, about 10 microliters are applied. This again takes place at atmospheric pressure.
  • the applied liquid penetrates at least partially into the microfluidic structure of the microfluidic system.
  • the microfluidic system can be pre-cooled, for example by placing it on a cooled storage surface, which in turn was pre-cooled, for example, at about -50 ° C.
  • the described method can be carried out, for example, with a cholesterol reagent which contains a surface-active substance.
  • reagents in dried form within the microfluidic structure of the microfluidic system with a desired distribution, for example a substantially homogeneous distribution.
  • the application of the reagent solution or suspension allows easy penetration of the reagent (s) into the microstructure. Subsequently, the drying is then carried out by lyophilization.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Drying Of Solid Materials (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
EP08019462.4A 2008-11-06 2008-11-06 Procédé destiné à la préparation d'un réactif séché dans un système microfluidique Not-in-force EP2198964B8 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP08019462.4A EP2198964B8 (fr) 2008-11-06 2008-11-06 Procédé destiné à la préparation d'un réactif séché dans un système microfluidique
US12/573,472 US8790932B2 (en) 2008-11-06 2009-10-05 Method for providing a dried reagent in a microfluidic system and microfluidic system
CA2684268A CA2684268A1 (fr) 2008-11-06 2009-11-03 Procede de fourniture d'un reactif sec dans un systeme microfluidique et systeme microfluidique connexe
JP2009254147A JP2010112953A (ja) 2008-11-06 2009-11-05 微小流体システムにおける乾燥試薬の提供方法及び微小流体システム
CN200910212006A CN101737989A (zh) 2008-11-06 2009-11-06 在微流体系统中提供干燥试剂的方法和微流体系统

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP08019462.4A EP2198964B8 (fr) 2008-11-06 2008-11-06 Procédé destiné à la préparation d'un réactif séché dans un système microfluidique

Publications (3)

Publication Number Publication Date
EP2198964A1 true EP2198964A1 (fr) 2010-06-23
EP2198964B1 EP2198964B1 (fr) 2013-01-02
EP2198964B8 EP2198964B8 (fr) 2013-04-24

Family

ID=40445241

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08019462.4A Not-in-force EP2198964B8 (fr) 2008-11-06 2008-11-06 Procédé destiné à la préparation d'un réactif séché dans un système microfluidique

Country Status (5)

Country Link
US (1) US8790932B2 (fr)
EP (1) EP2198964B8 (fr)
JP (1) JP2010112953A (fr)
CN (1) CN101737989A (fr)
CA (1) CA2684268A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130340612A1 (en) * 2012-06-22 2013-12-26 Mark William Ackley High Rate Compositions
US10232367B2 (en) 2013-07-05 2019-03-19 Thinxxs Microtechnology Ag Flow cell with an integrated dry substance
WO2024038109A1 (fr) 2022-08-17 2024-02-22 Thinxxs Microtechnology Gmbh Cuve à circulation microfluidique, procédé de production, utilisation et dispositif d'analyse

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2930133T3 (es) * 2010-03-09 2022-12-07 Ande Corp Biochip con almacenamiento de reactivo
US8720036B2 (en) 2010-03-09 2014-05-13 Netbio, Inc. Unitary biochip providing sample-in to results-out processing and methods of manufacture
US10946376B2 (en) 2013-07-05 2021-03-16 Thinxxs Microtechnology Ag Carrier element for introducing a dry substance into a flow cell
US10300486B2 (en) 2015-07-17 2019-05-28 Stat-Diagnostica & Innovation, S.L. Dry chemistry container
US11311885B2 (en) 2016-06-02 2022-04-26 Integrated Nano-Technologies, Inc. System and method for confining reagents within a fluidic device
WO2018194700A1 (fr) * 2017-04-20 2018-10-25 Hewlett-Packard Development Company, L.P. Système de réaction microfluidique
DE102018200520A1 (de) * 2018-01-15 2019-07-18 Robert Bosch Gmbh Verfahren zum Bereitstellen einer Lösung der Substanz in einer mikrofluidischen Vorrichtung
CN109174217B (zh) * 2018-08-07 2019-12-31 浙江大学 用于合成反应中实现干燥过程的微流控芯片及其方法
US12582984B1 (en) 2020-07-02 2026-03-24 Argonaut Manufacturing Services, Inc. Method for lyophilization and device thereof

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993004195A1 (fr) 1991-08-19 1993-03-04 Abaxis, Inc. Compositions de reactifs utilises dans des tests analytiques
WO2003035909A2 (fr) * 2001-10-26 2003-05-01 Ntu Ventures Pte Ltd Methode de detection d'une maladie
US20040209353A1 (en) * 2002-12-12 2004-10-21 Chiron Corporation Biological sample storage device and method for biological sample contamination testing
US20070054270A1 (en) * 2003-03-23 2007-03-08 Gyros Patent Ab Preloaded microfluidic devices
US20070259348A1 (en) 2005-05-03 2007-11-08 Handylab, Inc. Lyophilized pellets
US20070280857A1 (en) * 2006-06-02 2007-12-06 Applera Corporation Devices and Methods for Positioning Dried Reagent In Microfluidic Devices
EP1916524A1 (fr) 2006-09-27 2008-04-30 Roche Diagnostics GmbH Elément d'essai rotatif

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5102788A (en) * 1988-11-21 1992-04-07 Hygeia Sciences, Inc. Immunoassay including lyophilized reactant mixture

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993004195A1 (fr) 1991-08-19 1993-03-04 Abaxis, Inc. Compositions de reactifs utilises dans des tests analytiques
WO2003035909A2 (fr) * 2001-10-26 2003-05-01 Ntu Ventures Pte Ltd Methode de detection d'une maladie
US20040209353A1 (en) * 2002-12-12 2004-10-21 Chiron Corporation Biological sample storage device and method for biological sample contamination testing
US20070054270A1 (en) * 2003-03-23 2007-03-08 Gyros Patent Ab Preloaded microfluidic devices
US20070259348A1 (en) 2005-05-03 2007-11-08 Handylab, Inc. Lyophilized pellets
US20070280857A1 (en) * 2006-06-02 2007-12-06 Applera Corporation Devices and Methods for Positioning Dried Reagent In Microfluidic Devices
EP1916524A1 (fr) 2006-09-27 2008-04-30 Roche Diagnostics GmbH Elément d'essai rotatif

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130340612A1 (en) * 2012-06-22 2013-12-26 Mark William Ackley High Rate Compositions
US9533280B2 (en) * 2012-06-22 2017-01-03 Praxair Technology, Inc. High rate compositions
US10232367B2 (en) 2013-07-05 2019-03-19 Thinxxs Microtechnology Ag Flow cell with an integrated dry substance
WO2024038109A1 (fr) 2022-08-17 2024-02-22 Thinxxs Microtechnology Gmbh Cuve à circulation microfluidique, procédé de production, utilisation et dispositif d'analyse

Also Published As

Publication number Publication date
EP2198964B1 (fr) 2013-01-02
US8790932B2 (en) 2014-07-29
US20100112717A1 (en) 2010-05-06
CN101737989A (zh) 2010-06-16
CA2684268A1 (fr) 2010-05-06
JP2010112953A (ja) 2010-05-20
EP2198964B8 (fr) 2013-04-24

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