EP1438567B1 - Verfahren und systeme zur mikrofluidischen verarbeitung - Google Patents
Verfahren und systeme zur mikrofluidischen verarbeitung Download PDFInfo
- Publication number
- EP1438567B1 EP1438567B1 EP02715213.1A EP02715213A EP1438567B1 EP 1438567 B1 EP1438567 B1 EP 1438567B1 EP 02715213 A EP02715213 A EP 02715213A EP 1438567 B1 EP1438567 B1 EP 1438567B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- microfluidic
- sample
- lysing
- zone
- cell
- 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.)
- Expired - Lifetime
Links
Images
Classifications
-
- 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
-
- 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
- B01L2200/06—Fluid handling related problems
- B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
-
- 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
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
-
- 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
- B01L2300/0636—Integrated biosensor, microarrays
-
- 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
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
-
- 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
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
Definitions
- Another aspect of the present disclosure relates to a microfluidic system and method for processing a particle-containing fluid, such as, for example, a liquid containing bacterial cells or human cells.
- a particle-containing fluid such as, for example, a liquid containing bacterial cells or human cells.
- the system includes a lysing zone to receive the cell-containing sample and a positioning element to position the cell-containing sample in a lysing position in the vicinity of a lysing mechanism.
- the lysing mechanism releases intracellular material, such as DNA or RNA, from the cells.
- the lysing mechanism includes electrodes for generating an electric field sufficient to release intracellular contents from the cells.
- the lysing mechanism may lyse the cells using chemical, heat and/or ultrasonic techniques or any combination of these techniques.
- actuator 170 of the microdroplet preparation module 158 drives a microdroplet into cell lysis module 160.
- vented positioning element 200 positions microdroplet 802 in a lysing position with respect to electrodes 954. More specifically, as the microdroplet arrives in lysing module 160 it passes the opening of positioning element 200, because second positioning element 206 inhibits the microdroplet from flowing into vent 202.
- the propulsion gas from actuator 170 dissipates through vent 202, thereby substantially equalizing gas pressure upstream of microdroplet 802 with a pressure downstream of microdroplet 802.
- the microdroplet stops movement at a lysing position just downstream from barrier 200.
- substantially all of microdroplet 802 is disposed between an upstream edge 212 and a downstream edge 214 of electrodes 954.
- Reagent input module 152 is essentially the same as microdroplet formation module 158, however, it is specifically designed for formation of a microdroplet of reagent having a predetermined volume which will yield a desired ratio of reagent to sample when mixed with the microdroplet from cell lysing module 160.
- Module 152 includes an input port 420, a valve 422, and an actuator 172, each of which joins a reagent source channel 428.
- An overflow channel 424, which also joins reagents source channel 428, may also be provided.
- Actuator 172 may include a second positioning element 432 to prevent liquid from entering therein.
- the upstream gas dissipates through vent 508, thereby reducing the upstream pressure.
- the pressure reduction which preferably equalizes the downstream and upstream pressures, reduces or eliminates the motive force tending to urge the microfluidic sample downstream.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Hematology (AREA)
- Dispersion Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Read Only Memory (AREA)
Claims (9)
- Mikrofluidische Vorrichtung (110) zum Verarbeiten einer zellenhaltigen mikrofluidischen Probe, umfassend:ein Lysiermodul (300), das zum Aufnehmen einer zellenhaltigen mikrofluidischen Probe konfiguriert ist, wobei das Lysiermodul eine Lysierzone (302) aufweist, wobei die mikrofluidische Probe eine Flüssigkeit ist;ein Positionierelement (312), das zum Verhindern der Stromabwärtsbewegung der mikrofluidischen Probe zum Positionieren der mikrofluidischen Probe in einer Lysierposition konfiguriert ist;einen Lysiermechanismus (308) innerhalb der Lysierzone (302) zum Freisetzen von intrazellulärem Inhalt aus Zellen innerhalb der Lysierzone undeinen Gasaktor (314), der stromaufwärts von dem Positionierelement (312) und der Lysierzone (302) angeordnet ist, so dass ein erster Teil der mikrofluidischen Probe stromaufwärts von dem Gasaktor (314) angeordnet ist und ein zweiter Teil der mikrofluidischen Probe stromabwärts von dem Gasaktor (314) und stromaufwärts des Positionierelements (312) angeordnet ist, wobei der Gasaktor (314) zum Bereitstellen eines Gasdrucks konfiguriert ist, der ausreicht, um ein Mikrotröpfchen (304) mit einem vorbestimmten Volumen, das einen aus Zellen der zellenhaltigen mikrofluidischen Probe freigesetzten intrazellulären Inhalt umfasst, innerhalb der Lysierzone (302) durch Trennen des zweiten Teils der mikrofluidischen Probe vom ersten Teil der mikrofluidischen Probe und Bewegen des zweiten Teils der mikrofluidischen Probe zu einem Ort stromabwärts des Lysiermechanismus (308) und des Positionierelements (312) bereitzustellen.
- Mikrofluidische Vorrichtung (110) nach Anspruch 1, wobei die Vorrichtung einen Träger (130, 132) aufweist und wobei der Lysiermechanismus (308) und der Gasaktor (314) mit dem Träger einstückig sind.
- Mikrofluidische Vorrichtung (110) nach Anspruch 1 oder 2, wobei der Gasaktor (314) eine Wärmequelle zum Erhitzen einer Gasmenge, um dadurch einen Druck des Gases zu erhöhen, aufweist.
- Mikrofluidische Vorrichtung (110) nach einem der vorhergehenden Ansprüche, wobei das Positionierelement (312) eine Öffnung aufweist, um einen Gasdruck stromaufwärts der zellenhaltigen mikrofluidischen Probe mit einem Gasdruck stromabwärts der zellenhaltigen mikrofluidischen Probe im Wesentlichen auszugleichen, wenn die zellenhaltige mikrofluidische Probe in der Lysierposition ist, um dadurch die Stromabwärtsbewegung der zellenhaltigen mikrofluidischen Probe stromabwärts von der Lysierposition zu verhindern.
- Mikrofluidisches Verfahren zum Verarbeiten einer zellenhaltigen mikrofluidischen Probe, umfassend:mit einem Positionierelement (312) Positionieren der zellenhaltigen mikrofluidischen Probe in einer Lysierposition in Bezug auf einen Lysiermechanismus (308) einer Lysierzone (302) eines Lysiermoduls (300) einer mikrofluidischen Vorrichtung (110), wobei die zellenhaltige mikrofluidische Probe eine zellenhaltige Flüssigkeit umfasst;Betätigen eines Lysiermechanismus (308) zum Freisetzen von intrazellulärem Material aus Zellen der zellenhaltigen mikrofluidischen Probe;Betätigen eines Gasaktors (314), der stromaufwärts des Positionierelements (312) und der Lysierzone (302) angeordnet ist, um einen Gasdruck bereitzustellen, der ausreicht zum Trennen eines Teils der zellenhaltigen mikrofluidischen Probe, der stromabwärts des Gasaktors (314) und stromaufwärts des Positionierelements (312) ist, von einem Teil der zellenhaltigen mikrofluidischen Probe, der stromaufwärts des Gasaktors (314) ist, und zum Bewegen des stromabwärtigen Teils der zellenhaltigen mikrofluidischen Probe zu einem Ort stromabwärts des Lysiermechanismus (308) und des Positionierelements (312), wobei der stromabwärtige Teil der mikrofluidischen Probe ein Mikrotröpfchen (304) ist, das aus Zellen der zellenhaltigen mikrofluidischen Probe freigesetztes intrazelluläres Material umfasst und ein vorbestimmtes Volumen hat.
- Mikrofluidisches Verfahren nach Anspruch 1, wobei der Positionierungsschritt das Inkontaktbringen der stromabwärtigen Oberfläche der mikrofluidischen Probe mit einem hydrophoben Material umfasst.
- Mikrofluidisches Verfahren nach einem der Ansprüche 5 oder 6, wobei der Positionierungsschritt das Vergrößern eines Krümmungsradius der mikrofluidischen Probe umfasst.
- Mikrofluidisches Verfahren nach einem der Ansprüche 5 bis 7, wobei der Positionierungsschritt das im Wesentlichen Ausgleichen eines Gasdrucks stromaufwärts der mikrofluidischen Probe mit einem Gasdruck stromabwärts der mikrofluidischen Probe umfasst.
- Mikrofluidisches Verfahren nach einem der Ansprüche 5 bis 8, wobei der zweite Teil der mikrofluidischen Probe weniger als etwa 90 Prozent der zellenhaltigen mikrofluidischen Probe umfasst.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18185265.8A EP3427834A1 (de) | 2001-07-26 | 2002-03-27 | Verfahren und systeme zur mikrofluidischen verarbeitung |
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14519 | 1998-01-28 | ||
US30763801P | 2001-07-26 | 2001-07-26 | |
US307638P | 2001-07-26 | ||
US10/014,520 US7270786B2 (en) | 2001-03-28 | 2001-12-14 | Methods and systems for processing microfluidic samples of particle containing fluids |
US14520 | 2001-12-14 | ||
US10/014,519 US7192557B2 (en) | 2001-03-28 | 2001-12-14 | Methods and systems for releasing intracellular material from cells within microfluidic samples of fluids |
US75371 | 2002-02-15 | ||
US10/075,371 US7323140B2 (en) | 2001-03-28 | 2002-02-15 | Moving microdroplets in a microfluidic device |
PCT/US2002/009440 WO2003012406A1 (en) | 2001-07-26 | 2002-03-27 | Methods and systems for microfluidic processing |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP18185265.8A Division EP3427834A1 (de) | 2001-07-26 | 2002-03-27 | Verfahren und systeme zur mikrofluidischen verarbeitung |
Publications (3)
Publication Number | Publication Date |
---|---|
EP1438567A1 EP1438567A1 (de) | 2004-07-21 |
EP1438567A4 EP1438567A4 (de) | 2010-06-02 |
EP1438567B1 true EP1438567B1 (de) | 2018-07-25 |
Family
ID=27486401
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP02715213.1A Expired - Lifetime EP1438567B1 (de) | 2001-07-26 | 2002-03-27 | Verfahren und systeme zur mikrofluidischen verarbeitung |
EP18185265.8A Withdrawn EP3427834A1 (de) | 2001-07-26 | 2002-03-27 | Verfahren und systeme zur mikrofluidischen verarbeitung |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP18185265.8A Withdrawn EP3427834A1 (de) | 2001-07-26 | 2002-03-27 | Verfahren und systeme zur mikrofluidischen verarbeitung |
Country Status (4)
Country | Link |
---|---|
EP (2) | EP1438567B1 (de) |
JP (1) | JP4596776B2 (de) |
ES (1) | ES2683698T3 (de) |
WO (1) | WO2003012406A1 (de) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6048734A (en) | 1995-09-15 | 2000-04-11 | The Regents Of The University Of Michigan | Thermal microvalves in a fluid flow method |
US6692700B2 (en) | 2001-02-14 | 2004-02-17 | Handylab, Inc. | Heat-reduction methods and systems related to microfluidic devices |
US7323140B2 (en) | 2001-03-28 | 2008-01-29 | Handylab, Inc. | Moving microdroplets in a microfluidic device |
US6852287B2 (en) | 2001-09-12 | 2005-02-08 | Handylab, Inc. | Microfluidic devices having a reduced number of input and output connections |
US7829025B2 (en) | 2001-03-28 | 2010-11-09 | Venture Lending & Leasing Iv, Inc. | Systems and methods for thermal actuation of microfluidic devices |
US7010391B2 (en) | 2001-03-28 | 2006-03-07 | Handylab, Inc. | Methods and systems for control of microfluidic devices |
US8895311B1 (en) | 2001-03-28 | 2014-11-25 | Handylab, Inc. | Methods and systems for control of general purpose microfluidic devices |
EP2407243B1 (de) * | 2003-07-31 | 2020-04-22 | Handylab, Inc. | Mehrschichtige mikrofluidische vorrichtung |
US7156117B2 (en) | 2004-03-31 | 2007-01-02 | Lifescan Scotland Limited | Method of controlling the movement of fluid through a microfluidic circuit using an array of triggerable passive valves |
US7665303B2 (en) | 2004-03-31 | 2010-02-23 | Lifescan Scotland, Ltd. | Method of segregating a bolus of fluid using a pneumatic actuator in a fluid handling circuit |
US7059352B2 (en) | 2004-03-31 | 2006-06-13 | Lifescan Scotland | Triggerable passive valve for use in controlling the flow of fluid |
US8852862B2 (en) | 2004-05-03 | 2014-10-07 | Handylab, Inc. | Method for processing polynucleotide-containing samples |
ES2553097T3 (es) | 2004-05-03 | 2015-12-04 | Handylab, Inc. | Procesamiento de muestras que contienen polinucleótidos |
US10900066B2 (en) | 2006-03-24 | 2021-01-26 | Handylab, Inc. | Microfluidic system for amplifying and detecting polynucleotides in parallel |
US11806718B2 (en) | 2006-03-24 | 2023-11-07 | Handylab, Inc. | Fluorescence detector for microfluidic diagnostic system |
EP2001990B1 (de) | 2006-03-24 | 2016-06-29 | Handylab, Inc. | Integriertes system zur verarbeitung von mikrofluidischen proben und verwendungsverfahren |
US7998708B2 (en) | 2006-03-24 | 2011-08-16 | Handylab, Inc. | Microfluidic system for amplifying and detecting polynucleotides in parallel |
US8765076B2 (en) | 2006-11-14 | 2014-07-01 | Handylab, Inc. | Microfluidic valve and method of making same |
WO2008060604A2 (en) | 2006-11-14 | 2008-05-22 | Handylab, Inc. | Microfluidic system for amplifying and detecting polynucleotides in parallel |
US9186677B2 (en) | 2007-07-13 | 2015-11-17 | Handylab, Inc. | Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples |
US8105783B2 (en) | 2007-07-13 | 2012-01-31 | Handylab, Inc. | Microfluidic cartridge |
US8133671B2 (en) | 2007-07-13 | 2012-03-13 | Handylab, Inc. | Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples |
US8287820B2 (en) | 2007-07-13 | 2012-10-16 | Handylab, Inc. | Automated pipetting apparatus having a combined liquid pump and pipette head system |
JP5651011B2 (ja) | 2007-07-13 | 2015-01-07 | ハンディーラブ インコーポレイテッド | ポリヌクレオチド捕捉材料およびその使用方法 |
US20090136385A1 (en) | 2007-07-13 | 2009-05-28 | Handylab, Inc. | Reagent Tube |
US9618139B2 (en) | 2007-07-13 | 2017-04-11 | Handylab, Inc. | Integrated heater and magnetic separator |
US8182763B2 (en) | 2007-07-13 | 2012-05-22 | Handylab, Inc. | Rack for sample tubes and reagent holders |
USD787087S1 (en) | 2008-07-14 | 2017-05-16 | Handylab, Inc. | Housing |
ES2769028T3 (es) | 2011-04-15 | 2020-06-24 | Becton Dickinson Co | Termociclador microfluídico de barrido en tiempo real |
USD692162S1 (en) | 2011-09-30 | 2013-10-22 | Becton, Dickinson And Company | Single piece reagent holder |
DK2761305T3 (da) | 2011-09-30 | 2017-11-20 | Becton Dickinson Co | Forenet reagensstrimmel |
CN104040238B (zh) | 2011-11-04 | 2017-06-27 | 汉迪拉布公司 | 多核苷酸样品制备装置 |
WO2013116769A1 (en) | 2012-02-03 | 2013-08-08 | Becton, Dickson And Company | External files for distribution of molecular diagnostic tests and determination of compatibility between tests |
WO2020112081A1 (en) * | 2018-11-26 | 2020-06-04 | Hewlett-Packard Development Company, L.P. | Microfluidic devices |
CN112023990B (zh) * | 2019-06-03 | 2023-06-23 | 利多(香港)有限公司 | 一种微流控检测芯片及制造方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US6130098A (en) * | 1995-09-15 | 2000-10-10 | The Regents Of The University Of Michigan | Moving microdroplets |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5304487A (en) * | 1992-05-01 | 1994-04-19 | Trustees Of The University Of Pennsylvania | Fluid handling in mesoscale analytical devices |
US5639423A (en) * | 1992-08-31 | 1997-06-17 | The Regents Of The University Of Calfornia | Microfabricated reactor |
US6168948B1 (en) * | 1995-06-29 | 2001-01-02 | Affymetrix, Inc. | Miniaturized genetic analysis systems and methods |
US5856174A (en) * | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US5863502A (en) * | 1996-01-24 | 1999-01-26 | Sarnoff Corporation | Parallel reaction cassette and associated devices |
JPH10108666A (ja) * | 1996-10-04 | 1998-04-28 | Asahi Medical Co Ltd | 中空糸型培養器 |
WO1998022625A1 (en) | 1996-11-20 | 1998-05-28 | The Regents Of The University Of Michigan | Microfabricated isothermal nucleic acid amplification devices and methods |
DE69934449T2 (de) * | 1998-03-12 | 2007-09-27 | Miltenyi Biotech Gmbh | Mikrokolonnen-System für Magnettrennung |
JP4074713B2 (ja) * | 1998-07-29 | 2008-04-09 | 財団法人川村理化学研究所 | 送液デバイス及びその製造方法 |
JP2000166535A (ja) * | 1998-12-10 | 2000-06-20 | Nippon Laser Denshi Kk | 微量分注針体 |
DE19948473A1 (de) * | 1999-10-08 | 2001-04-12 | Nmi Univ Tuebingen | Verfahren und Vorrichtung zum Messen an in einer flüssigen Umgebung befindlichen Zellen |
US6272939B1 (en) * | 1999-10-15 | 2001-08-14 | Applera Corporation | System and method for filling a substrate with a liquid sample |
-
2002
- 2002-03-27 JP JP2003517550A patent/JP4596776B2/ja not_active Expired - Lifetime
- 2002-03-27 EP EP02715213.1A patent/EP1438567B1/de not_active Expired - Lifetime
- 2002-03-27 EP EP18185265.8A patent/EP3427834A1/de not_active Withdrawn
- 2002-03-27 ES ES02715213.1T patent/ES2683698T3/es not_active Expired - Lifetime
- 2002-03-27 WO PCT/US2002/009440 patent/WO2003012406A1/en active Application Filing
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6130098A (en) * | 1995-09-15 | 2000-10-10 | The Regents Of The University Of Michigan | Moving microdroplets |
Also Published As
Publication number | Publication date |
---|---|
JP4596776B2 (ja) | 2010-12-15 |
ES2683698T3 (es) | 2018-09-27 |
EP1438567A4 (de) | 2010-06-02 |
EP3427834A1 (de) | 2019-01-16 |
WO2003012406A1 (en) | 2003-02-13 |
JP2005514718A (ja) | 2005-05-19 |
EP1438567A1 (de) | 2004-07-21 |
WO2003012406A9 (en) | 2003-03-20 |
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