ES2626848T3 - Dispositivos y métodos para la separación de partículas basada en la forma - Google Patents
Dispositivos y métodos para la separación de partículas basada en la forma Download PDFInfo
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- ES2626848T3 ES2626848T3 ES12856833.4T ES12856833T ES2626848T3 ES 2626848 T3 ES2626848 T3 ES 2626848T3 ES 12856833 T ES12856833 T ES 12856833T ES 2626848 T3 ES2626848 T3 ES 2626848T3
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03B—SEPARATING SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS
- B03B5/00—Washing granular, powdered or lumpy materials; Wet separating
- B03B5/48—Washing granular, powdered or lumpy materials; Wet separating by mechanical classifiers
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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
- 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
- B01L3/502746—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 the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves
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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
- 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
- B01L3/502761—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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
-
- 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
- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0636—Focussing flows, e.g. to laminate flows
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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
- 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
- B01L2200/0652—Sorting or classification of particles or molecules
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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
- 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
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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
- 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
- B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
-
- 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
- B01L2300/088—Channel loops
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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
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
- G01N2015/0288—Sorting the particles
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
- G01N2015/0294—Particle shape
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Dispersion Chemistry (AREA)
- Pathology (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Clinical Laboratory Science (AREA)
- Hematology (AREA)
- Fluid Mechanics (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Separation Of Solids By Using Liquids Or Pneumatic Power (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Un sistema de clasificación de partículas, que comprende: una entrada; un microcanal (14) de concentración inercial dispuesto en un sustrato y que tiene una región (18) que se expande aguas abajo en un extremo distal, en donde la entrada (12) se conecta a un extremo aguas arriba del microcanal; una fuente (30) de partículas con formas diferentes conectada a la entrada, en la que la fuente de partículas con formas diferentes se configuran para su introducción continua en la entrada; una pluralidad de salidas (20) conectada al microcanal en la región que se expande aguas abajo; caracterizado porque el sistema comprende además un controlador de presión conectado a la pluralidad de salidas por las líneas de fluidos, en donde el controlador de presión (23) ejerce presiones variables para ajustar la resistencia respectiva del fluido en la pluralidad de salidas.
Description
etapas de crecimiento celular, en las que por ejemplo, las bacterias con forma de vara pueden tener hasta el doble de su longitud.
La separación basada en la forma usando efectos inerciales también puede usarse para la clasificación de células
5 de levadura y la sincronización del ciclo celular. La comprensión del ciclo celular es el sujeto de la investigación actual, que a menudo explora el uso de células de levadura (S. Cerevisiae) debido a la genética bien conocida y a los cambios de forma característicos); las células de levadura germinativas se alargan a partir de una esfera a un gemelo biesférico o a un agregado mayor. Usando el sistema de clasificación de partículas de la FIG. 7C (RAc = 0,64, siete salidas con α1:2 = 3/4, α1:3 = 1/2, α1:4 = 1/4), la clasificación de levaduras se llevó a cabo a un caudal de 60
10 μl/min. La levadura se cultivó en caldo de soja tríptico (CST) en un agitador incubado (37 ºC) durante un día antes del experimento de separación. La suspensión se cultivó se diluyó en TFS a una concentración no limitante de 1,5x106 células/ml y luego, de manera similar a las perlas, se inyectó a diversos caudales usando una bomba de jeringa Harvard Apparatus y una jeringa de vidrio Hamilton. El comportamiento de separación se capturó a través de la formación de imágenes a alta velocidad, siendo el contenido de cada salida analizado mediante el recuento
15 inmediato con un hemocitómetro (Quick-Read). Se observaron las morfologías de las células de levadura y se categorizaron, en función de su estado de ciclo, en (i) individuales pequeñas que no se dividen, (II) individuales grandes, (iii) levadura germinativa, (IV) como dobletes, y (v) agregados que se componen de tres o más células.
La FIG. 9A ilustra una imagen microscópica de las células en la entrada del dispositivo. Las células se categorizan
20 en cinco grupos: individuales pequeñas (recuadro superior), individuales grandes (segundo a partir del recuadro superior), germinativas (tercero a partir del recuadro superior), como dobletes (cuarto a partir del recuadro superior) y agregados (último recuadro). La FIG. 9B ilustra imágenes respectivas de la salida 2 y la salida 3. Las individuales tenían un alto rendimiento de extracción en la salida 2, mientras que en la salida 3, la pureza de las células germinativas aumentó.
25 Se descubrió que las individuales que no se dividen tenían un alto rendimiento de extracción en las salidas 2 y 6 (90 % de las individuales pequeñas y 91 % de las individuales grandes se recuperan en estas salidas como se aprecia en la FIG. 9C), con una pureza de hasta el 94 % (FIG. 9D), mientras que las células de levadura germinativas se recogieron principalmente en las salidas 3 y 5 (54 % de levadura germinativa, con una pureza de
30 hasta el 31 %, en comparación con una pureza del 6,6 % en la entrada). La mayor producción del sistema de clasificación de partículas (60 µl/min, es decir, 1.500 células/s en comparación con 100 células/s) se podría aumentar aún más por la paralelización de los canales de concentración, mientras que la pureza y enriquecimiento especialmente necesarios para esta aplicación de sincronización mejora con la conexión en cascada de varios dispositivos en serie.
35 En los experimentos se descubrió que un sistema de clasificación de partículas con RAc = 0,53 (An = 25 μm, Al = 47 μm) en Q = 40 µl/min que tiene cinco (5) salidas con resistencias iguales es el mejor dispositivo para separar varas largas (1:5) de 6 µm a partir de esferas y varas cortas (1:3), mientras que la separación de esferas de 6 µm de los dos tipos de varas se realiza mejor usando RAc = 0,64 (An = 30 µm, Al = 47 μm) en Q = 80 µl/min con cinco (5)
40 salidas con α1:2 = 3/4 y α1:3 = 1/2. El mejor dispositivo para la separación de los tres tipos de partículas de 6 µm era RAc = 0,64 (An = 30 µm, Al = 47 μm), en Q = 70 µl/min con siete (7) salidas con α1:2 = 3/4, α1:3 = 1/2, α1:4 = 1/4. Para esferas de partículas de 3 μm podría separarse mejor de los dos tipos de varas con RAc = 0,53 (An = 25 μm, Al = 47 μm) del dispositivo en Q = 80 µl/min con cinco (5) salidas con α1:2 = % y α1:3 = 1/2. El enriquecimiento de la levadura germinativa de la población total de células fue exitoso usando un dispositivo con RAc = 0,64 (An = 30 µm, Al = 47
45 μm) con siete (7) salidas con α1:2 = 3/4, α1 3 = 1/2, α1:4 = ¼. Las condiciones pueden ser optimizadas para otros modos de separación deseados, tales como el enriquecimiento de individuales, etc.
11
Claims (1)
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imagen1 imagen2
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161541934P | 2011-09-30 | 2011-09-30 | |
| US201161541934P | 2011-09-30 | ||
| US201261606287P | 2012-03-02 | 2012-03-02 | |
| US201261606287P | 2012-03-02 | ||
| PCT/US2012/057631 WO2013089883A2 (en) | 2011-09-30 | 2012-09-27 | Devices and methods for shape-based particle separation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2626848T3 true ES2626848T3 (es) | 2017-07-26 |
Family
ID=48613336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12856833.4T Active ES2626848T3 (es) | 2011-09-30 | 2012-09-27 | Dispositivos y métodos para la separación de partículas basada en la forma |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9333510B2 (es) |
| EP (1) | EP2761303B1 (es) |
| JP (1) | JP6031109B2 (es) |
| KR (1) | KR20140084075A (es) |
| CN (1) | CN103959069B (es) |
| AU (1) | AU2012352879B2 (es) |
| CA (1) | CA2850335A1 (es) |
| ES (1) | ES2626848T3 (es) |
| WO (1) | WO2013089883A2 (es) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11243494B2 (en) | 2002-07-31 | 2022-02-08 | Abs Global, Inc. | Multiple laminar flow-based particle and cellular separation with laser steering |
| US10908066B2 (en) | 2010-11-16 | 2021-02-02 | 1087 Systems, Inc. | Use of vibrational spectroscopy for microfluidic liquid measurement |
| US8961904B2 (en) | 2013-07-16 | 2015-02-24 | Premium Genetics (Uk) Ltd. | Microfluidic chip |
| US11796449B2 (en) | 2013-10-30 | 2023-10-24 | Abs Global, Inc. | Microfluidic system and method with focused energy apparatus |
| WO2016010861A1 (en) * | 2014-07-14 | 2016-01-21 | President And Fellows Of Harvard College | Systems and methods for improved performance of fluidic and microfluidic systems |
| US10180388B2 (en) | 2015-02-19 | 2019-01-15 | 1087 Systems, Inc. | Scanning infrared measurement system |
| US10591403B2 (en) | 2016-03-16 | 2020-03-17 | Georgia Tech Research Corporation | Multiplexed analysis of cell-materials in niches |
| US12128407B2 (en) * | 2016-04-15 | 2024-10-29 | Vortex Biosciences, Inc. | Microfluidic chips and cartridges and systems utilizing microfluidic chips and cartridges |
| US10471425B2 (en) | 2017-02-16 | 2019-11-12 | International Business Machines Corporation | Automated machine for sorting of biological fluids |
| US11326991B2 (en) * | 2017-11-14 | 2022-05-10 | Aerodyne Microsystems Inc. | Airborne particle detection with selective thermophoretic particle deflection |
| CN108405169B (zh) * | 2018-03-07 | 2020-03-10 | 中国工程物理研究院激光聚变研究中心 | 一种液体筛分微球装置 |
| US11229912B2 (en) | 2018-03-27 | 2022-01-25 | Hewlett-Packard Development Company, L.P. | Particle separation |
| SG11202010398RA (en) * | 2018-05-09 | 2020-11-27 | Hoffmann La Roche | Devices and methods for determining particle concentration in a sample |
| US11331670B2 (en) | 2018-05-23 | 2022-05-17 | Abs Global, Inc. | Systems and methods for particle focusing in microchannels |
| CN108872047B (zh) * | 2018-08-15 | 2021-02-26 | 军事科学院系统工程研究院卫勤保障技术研究所 | 一种微流控电阻抗检测区分微小粒子形状的系统及方法 |
| US10611995B2 (en) | 2018-08-15 | 2020-04-07 | Deepcell, Inc. | Systems and methods for particle analysis |
| US11815507B2 (en) | 2018-08-15 | 2023-11-14 | Deepcell, Inc. | Systems and methods for particle analysis |
| US20200070167A1 (en) * | 2018-08-31 | 2020-03-05 | Vortex Biosciences, Inc. | Processing systems for isolating and enumerating cells or particles |
| EP3899489B1 (en) | 2018-12-21 | 2025-04-09 | ABS Global, Inc. | System and methods for sub-population identification |
| US11524292B2 (en) * | 2019-02-21 | 2022-12-13 | International Business Machines Corporation | Programmable hydraulic resistor array for microfluidic chips |
| EP3955735B1 (en) | 2019-04-18 | 2024-05-22 | ABS Global, Inc. | System and process for continuous addition of cryoprotectant |
| US12053569B2 (en) | 2019-09-04 | 2024-08-06 | The Regents Of The University Of Michigan | Indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells |
| CN114901392B (zh) * | 2019-10-21 | 2024-10-29 | 南洋理工大学 | 使用离心力从全血中直接和可扩展地分离循环胞外囊泡 |
| US11628439B2 (en) * | 2020-01-13 | 2023-04-18 | Abs Global, Inc. | Single-sheath microfluidic chip |
| WO2022087299A1 (en) | 2020-10-21 | 2022-04-28 | Abs Global, Inc. | Methods and systems for processing genetic samples to determine identity or detect contamination |
| US12135270B2 (en) | 2020-11-23 | 2024-11-05 | Abs Global, Inc. | Modular flow cytometry systems and methods of processing samples |
| WO2022170340A1 (en) * | 2021-02-03 | 2022-08-11 | University Of Georgia Research Foundation, Inc. | Devices, kits, and methods for label-free inertial ferrohydrodynamic cell separation with high throughput and resolution |
| CN112973815B (zh) * | 2021-03-09 | 2022-06-03 | 西北大学 | 一种聚集非球形微游泳体的微流管道及一种过滤方法 |
| US12576194B2 (en) | 2021-06-29 | 2026-03-17 | Regents Of The University Of Michigan | Microfluidic flow control using direct-current peristaltic pump |
| CN113769797B (zh) * | 2021-09-02 | 2023-03-14 | 浙江理工大学 | 一种流固两相输运中的微尺度颗粒直径测定的方法 |
| USD1118965S1 (en) | 2021-11-12 | 2026-03-17 | Abs Global, Inc. | Flow cytometry device |
| CN118067593A (zh) * | 2022-11-22 | 2024-05-24 | 中国科学院深圳先进技术研究院 | 微流控分选芯片、控制设备、微流控分选系统及方法 |
| CN116673080B (zh) * | 2023-06-27 | 2025-09-02 | 深圳大学 | 微流控制装置的制备方法及黏弹性-惯性微流控分选装置 |
| CN119738236A (zh) * | 2024-12-30 | 2025-04-01 | 上海交通大学 | 一种生物检测芯片、检测方法及检测设备 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7735652B2 (en) * | 2006-06-01 | 2010-06-15 | The Trustees Of Princeton University | Apparatus and method for continuous particle separation |
| US8186913B2 (en) * | 2007-04-16 | 2012-05-29 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
| JP5304506B2 (ja) * | 2009-07-22 | 2013-10-02 | 富士ゼロックス株式会社 | 分級装置及び分級方法 |
| SG183468A1 (en) | 2010-03-04 | 2012-09-27 | Univ Singapore | Microfluidics sorter for cell detection and isolation |
| US8590710B2 (en) * | 2010-06-10 | 2013-11-26 | Samsung Electronics Co., Ltd. | Target particles-separating device and method using multi-orifice flow fractionation channel |
| US9090865B2 (en) * | 2010-10-29 | 2015-07-28 | The Regents Of The University Of California | Systems and methods for particle classification and sorting |
-
2012
- 2012-09-27 ES ES12856833.4T patent/ES2626848T3/es active Active
- 2012-09-27 JP JP2014533332A patent/JP6031109B2/ja active Active
- 2012-09-27 US US14/346,290 patent/US9333510B2/en active Active
- 2012-09-27 KR KR20147011199A patent/KR20140084075A/ko not_active Withdrawn
- 2012-09-27 WO PCT/US2012/057631 patent/WO2013089883A2/en not_active Ceased
- 2012-09-27 AU AU2012352879A patent/AU2012352879B2/en active Active
- 2012-09-27 CN CN201280059414.0A patent/CN103959069B/zh active Active
- 2012-09-27 EP EP12856833.4A patent/EP2761303B1/en active Active
- 2012-09-27 CA CA 2850335 patent/CA2850335A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP2761303A2 (en) | 2014-08-06 |
| WO2013089883A3 (en) | 2013-08-29 |
| AU2012352879A1 (en) | 2014-04-10 |
| EP2761303A4 (en) | 2015-06-03 |
| JP6031109B2 (ja) | 2016-11-24 |
| WO2013089883A2 (en) | 2013-06-20 |
| CN103959069B (zh) | 2016-02-24 |
| CA2850335A1 (en) | 2013-06-20 |
| KR20140084075A (ko) | 2014-07-04 |
| CN103959069A (zh) | 2014-07-30 |
| JP2015501136A (ja) | 2015-01-15 |
| US9333510B2 (en) | 2016-05-10 |
| US20140224710A1 (en) | 2014-08-14 |
| AU2012352879B2 (en) | 2017-01-05 |
| EP2761303B1 (en) | 2017-03-01 |
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