CN114011479B - 跨界面磁性分离 - Google Patents

跨界面磁性分离 Download PDF

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Publication number
CN114011479B
CN114011479B CN202111135982.1A CN202111135982A CN114011479B CN 114011479 B CN114011479 B CN 114011479B CN 202111135982 A CN202111135982 A CN 202111135982A CN 114011479 B CN114011479 B CN 114011479B
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chamber
liquid
pmp
transfer
analyte
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Chinese (zh)
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CN114011479A (zh
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D·M·凯尔索
A·K·阿加瓦尔
S·M·麦克法尔
T·韦斯特伯格
M·A·布泽尔
J·L·里德
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Northwestern University
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Northwestern University
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    • 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
    • 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
    • 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
    • B01L7/525—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 with physical movement of samples between temperature zones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation
    • 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
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • 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
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • 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
    • B01L2300/042—Caps; Plugs
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
    • B01L2300/166—Suprahydrophobic; Ultraphobic; Lotus-effect
    • 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
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces

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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)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Compounds Of Iron (AREA)
  • Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)
CN202111135982.1A 2017-06-06 2018-06-06 跨界面磁性分离 Active CN114011479B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111135982.1A CN114011479B (zh) 2017-06-06 2018-06-06 跨界面磁性分离

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201762515876P 2017-06-06 2017-06-06
US62/515,876 2017-06-06
CN202111135982.1A CN114011479B (zh) 2017-06-06 2018-06-06 跨界面磁性分离
PCT/US2018/036348 WO2018226891A1 (en) 2017-06-06 2018-06-06 Trans-interfacial magnetic separation
CN201880048221.2A CN111148572B (zh) 2017-06-06 2018-06-06 跨界面磁性分离

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CN114011479A CN114011479A (zh) 2022-02-08
CN114011479B true CN114011479B (zh) 2023-05-02

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US (2) US11673134B2 (cg-RX-API-DMAC7.html)
EP (1) EP3634634A4 (cg-RX-API-DMAC7.html)
JP (1) JP7168230B2 (cg-RX-API-DMAC7.html)
CN (2) CN114011479B (cg-RX-API-DMAC7.html)
AU (2) AU2018281310B2 (cg-RX-API-DMAC7.html)
CA (1) CA3065928C (cg-RX-API-DMAC7.html)
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Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3993908B1 (en) * 2019-07-03 2023-11-15 Siemens Healthcare Diagnostics Inc. Rotary platform for cell lysing and purification and method of use
AU2020407163A1 (en) 2019-12-16 2022-07-21 Minute Molecular Diagnostics, Inc. Lyophilized reagents
EP4275056A4 (en) 2021-01-29 2024-12-11 Abbott Diagnostics Scarborough, Inc. MAGNETIC PARTICLE AIR TRANSMISSION
WO2023097922A1 (zh) * 2021-11-30 2023-06-08 珠海黑马生物科技有限公司 一种全封闭全自动核酸提取试剂盒
CN114107035B (zh) * 2021-11-30 2022-06-03 珠海黑马生物科技有限公司 一种封闭式全自动核酸提取试剂盒
CA3245746A1 (en) * 2022-03-29 2023-10-05 Salus Discovery, LLC SYSTEMS AND METHODS FOR ISOLATING A TARGET CONTAINED IN A BIOLOGICAL SAMPLE
CN114657049B (zh) * 2022-05-12 2023-06-13 广州国家实验室 一种核酸扩增用卡盒

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101010592A (zh) * 2004-07-26 2007-08-01 拜奥默里克斯有限公司 将磁性粒子与流体分离、混合和浓缩的设备和方法及其在提纯方法中的用途
WO2011076860A1 (en) * 2009-12-23 2011-06-30 Atonomics A/S Device, method, and system for the quantitative detection of the presence of multiple target analytes
CN103384565A (zh) * 2010-09-29 2013-11-06 哈恩-席卡德应用研究学会 运输磁性粒子的方法

Family Cites Families (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3793445A (en) * 1970-04-29 1974-02-19 Wisconsin Alumni Res Found Reagent for radioimmunoassay
GB1575805A (en) * 1976-03-12 1980-10-01 Technicon Instr Automatic diagnostic apparatus
US5110727A (en) * 1987-04-03 1992-05-05 Cardiovascular Diagnostics, Inc. Method for performing coagulation assays accurately, rapidly and simply, using dry chemical reagents and paramagnetic particles
IL100866A (en) * 1991-02-06 1995-10-31 Igen Inc Method and apparatus for magnetic microparticulate based luminescence assay including plurality of magnets
JP2625577B2 (ja) * 1992-03-20 1997-07-02 アボツト・ラボラトリーズ 磁気標識した結合要素を用いた磁気制御型結合アッセイ
FI932866A0 (fi) * 1993-06-21 1993-06-21 Labsystems Oy Separeringsfoerfarande
US5395752A (en) * 1993-03-19 1995-03-07 Ciba Corning Diagnostics Corp. Long emission wavelength chemiluminescent compounds and their use in test assays
US6586193B2 (en) * 1996-04-25 2003-07-01 Genicon Sciences Corporation Analyte assay using particulate labels
CA2303165C (en) * 1997-09-22 2006-07-11 Chiron Corporation Buffers for stabilizing antigens
WO1999040098A1 (de) 1998-02-04 1999-08-12 Merck Patent Gmbh Verfahren zur isolierung und aufreinigung von nucleinsäuren
JP5219057B2 (ja) * 1998-07-31 2013-06-26 旭化成株式会社 微生物検出用抗体
CN1185492C (zh) * 1999-03-15 2005-01-19 清华大学 可单点选通式微电磁单元阵列芯片、电磁生物芯片及应用
CN1128023C (zh) * 1999-05-31 2003-11-19 中国科学院化工冶金研究所 从流体中分离磁性颗粒的连续式高梯度磁分离方法及装置
JP2003526523A (ja) * 2000-03-16 2003-09-09 エスアールアイ インターナショナル 微小実験デバイスおよび方法
DE10013990C2 (de) * 2000-03-22 2003-12-04 Invitek Biotechnik & Biodesign Polyfunktionelles Trägermaterial für die komplexe Nukleinsäureanalytik
WO2002072264A1 (en) * 2001-03-09 2002-09-19 Biomicro Systems, Inc. Method and system for microfluidic interfacing to arrays
EP1279961A3 (en) * 2001-07-23 2004-02-18 Norzyme, Inc. Non-isotopic method and kit for quantifying enzyme inhibitors
CN100442052C (zh) * 2002-08-15 2008-12-10 陕西西大北美基因股份有限公司 磁性荧光微球及其制备方法和采用该磁性荧光微球进行生物分子检测的方法
WO2004053075A2 (en) * 2002-12-05 2004-06-24 Diadexus, Inc. Compositions, splice variants and methods relating to breast specific genes and proteins
DE10356752A1 (de) * 2003-12-04 2005-06-30 Roche Diagnostics Gmbh Beschichtete Testelemente
CN101198707A (zh) * 2004-05-12 2008-06-11 内诺斯佩尔公司 基于生物条形码检测靶分析物
DE102004040785B4 (de) * 2004-08-23 2006-09-21 Kist-Europe Forschungsgesellschaft Mbh Mikrofluidisches System zur Isolierung biologischer Partikel unter Verwendung der immunomagnetischen Separation
WO2006071770A2 (en) 2004-12-23 2006-07-06 I-Stat Corporation Molecular diagnostics system and methods
DE102005039175A1 (de) * 2005-08-18 2007-02-22 Qiagen Gmbh Vorrichtung und Verfahren zum Abtrennen von magnetischen Partikeln aus einer Flüssigkeit
GB2436616A (en) * 2006-03-29 2007-10-03 Inverness Medical Switzerland Assay device and method
CN101529250A (zh) * 2006-08-18 2009-09-09 3M创新有限公司 使用声-机械检测系统检测的方法
CN1987464B (zh) * 2006-09-29 2012-03-14 浙江大学 磁捕获技术在NF-κB蛋白分离与检测中的应用方法
CN102027367B (zh) * 2008-02-29 2016-03-23 西北大学 促进生物反应的屏障
CN101251541A (zh) * 2008-04-11 2008-08-27 清华大学 无标记噬菌体展示蛋白质芯片及其制备和检测方法
GB0806771D0 (en) * 2008-04-12 2008-05-14 Spd Swiss Prec Diagnostics Gmb Assay devices comprising bubble-forming means
US8093064B2 (en) * 2008-05-15 2012-01-10 The Regents Of The University Of California Method for using magnetic particles in droplet microfluidics
JP5311518B2 (ja) 2008-10-06 2013-10-09 コーニンクレッカ フィリップス エヌ ヴェ マイクロ流体装置
JP5372167B2 (ja) 2008-12-16 2013-12-18 コーニンクレッカ フィリップス エヌ ヴェ 疎水性弁
US9156037B2 (en) * 2009-01-15 2015-10-13 Children's Medical Center Corporation Microfluidic device and uses thereof
RU2559541C2 (ru) * 2009-06-05 2015-08-10 Интедженкс Инк. Универсальная система подготовки образцов и применение в интегрированной системе анализа
US9272290B2 (en) 2009-07-17 2016-03-01 Koninklijke Philips N.V. Apparatus for the enrichment of magnetic particles
DE102009035941B8 (de) * 2009-08-03 2017-04-27 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Diagnostiksystem
CA2772020A1 (en) * 2009-08-31 2011-03-03 Mbio Diagnostics, Inc. Integrated sample preparation and analyte detection
CA2724106C (en) * 2009-12-10 2018-04-17 F. Hoffmann-La Roche Ag Multiwell plate and lid
WO2011091037A2 (en) * 2010-01-19 2011-07-28 President And Fellows Of Harvard College Rapid pathogen diagnostic device and method
US8603416B2 (en) 2010-02-26 2013-12-10 Wisconsin Alumni Research Foundation Device for and method of extracting a fraction from a biological sample
US8728410B2 (en) 2010-02-26 2014-05-20 Wisconsin Alumni Research Foundation Device for and method of extracting a fraction from a biological sample
US9677979B2 (en) * 2010-07-16 2017-06-13 Vanderbilt University Low resource processor using surface tension valves for extracting, concentrating and detecting molecular species
KR20130029128A (ko) * 2010-07-23 2013-03-21 베크만 컬터, 인코포레이티드 실시간 pcr용 용기
US9822356B2 (en) * 2012-04-20 2017-11-21 California Institute Of Technology Fluidic devices and systems for sample preparation or autonomous analysis
US9766166B2 (en) 2013-01-09 2017-09-19 Wisconsin Alumni Research Foundation Device and method incorporating a slideable lid for extracting a targeted fraction from a sample
US10564077B2 (en) 2012-09-05 2020-02-18 Wisconsin Alumni Research Foundation Device for and method of isolating and analyzing a fraction in a biological sample
US8728411B2 (en) 2012-09-05 2014-05-20 Wisconsin Alumni Research Foundation Device for and method of isolating a fraction in a biological sample
US9869675B2 (en) * 2013-03-13 2018-01-16 Vanderbilt University Low resource processor using surface tension valves for extracting, concentrating, and detecting whole cells
US11029310B2 (en) 2013-03-14 2021-06-08 Wisconsin Alumni Research Foundation Device and method for extracting a targeted fraction from a sample
US9952209B2 (en) * 2013-07-01 2018-04-24 The University Of Memphis Research Foundation Iron oxide-gold core-shell nanoparticles and uses thereof
GB201321430D0 (en) * 2013-12-04 2014-01-15 Spd Swiss Prec Diagnostics Gmbh Assay device
EP3080300B1 (en) * 2013-12-11 2020-09-02 Genapsys Inc. Systems and methods for biological analysis and computation
US10040062B2 (en) 2014-01-14 2018-08-07 Wisconsin Alumni Research Foundation Device and method for transferring a target between locations
CA2937975A1 (en) * 2014-01-27 2015-07-30 Brevitest Technologies, Llc Discontinuous fluidic systems for point-of-care analyte measurement
WO2016077067A2 (en) * 2014-10-27 2016-05-19 President And Fellows Of Harvard College Magnetic capture of a target from a fluid
US9518903B2 (en) 2015-01-13 2016-12-13 Gilson, Inc. Adapter for sliding magnetic particle separation
US10302634B2 (en) * 2015-07-01 2019-05-28 Ancera, Llc Tunable affinity system and method for ferrofluid-based capture assays

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101010592A (zh) * 2004-07-26 2007-08-01 拜奥默里克斯有限公司 将磁性粒子与流体分离、混合和浓缩的设备和方法及其在提纯方法中的用途
WO2011076860A1 (en) * 2009-12-23 2011-06-30 Atonomics A/S Device, method, and system for the quantitative detection of the presence of multiple target analytes
CN103384565A (zh) * 2010-09-29 2013-11-06 哈恩-席卡德应用研究学会 运输磁性粒子的方法

Also Published As

Publication number Publication date
AU2018281310A1 (en) 2020-01-02
CA3065928C (en) 2025-05-20
US20210146351A1 (en) 2021-05-20
AU2023237099B2 (en) 2025-10-02
EP3634634A1 (en) 2020-04-15
CA3065928A1 (en) 2018-12-13
EP3634634A4 (en) 2021-03-10
JP2020523570A (ja) 2020-08-06
CN111148572B (zh) 2022-05-06
AU2023237099A1 (en) 2023-10-12
JP7168230B2 (ja) 2022-11-09
WO2018226891A1 (en) 2018-12-13
US11673134B2 (en) 2023-06-13
US20240024865A1 (en) 2024-01-25
CN114011479A (zh) 2022-02-08
AU2018281310B2 (en) 2023-06-29
CN111148572A (zh) 2020-05-12

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