EP1325331A4 - Zusammensetzungen und verfahren zur trennung von wirksamen anteilen auf chips - Google Patents

Zusammensetzungen und verfahren zur trennung von wirksamen anteilen auf chips

Info

Publication number
EP1325331A4
EP1325331A4 EP01977391A EP01977391A EP1325331A4 EP 1325331 A4 EP1325331 A4 EP 1325331A4 EP 01977391 A EP01977391 A EP 01977391A EP 01977391 A EP01977391 A EP 01977391A EP 1325331 A4 EP1325331 A4 EP 1325331A4
Authority
EP
European Patent Office
Prior art keywords
sample
solution
cells
moieties
chamber
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.)
Withdrawn
Application number
EP01977391A
Other languages
English (en)
French (fr)
Other versions
EP1325331A1 (de
Inventor
Junquan Xu
Xiaobo Wang
Jing Cheng
Weiping Yang
Lei Wu
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.)
Aviva Biosciences Corp
Original Assignee
Aviva Biosciences Corp
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
Priority claimed from CNB001316494A external-priority patent/CN100392384C/zh
Priority claimed from US09/686,737 external-priority patent/US6858439B1/en
Application filed by Aviva Biosciences Corp filed Critical Aviva Biosciences Corp
Publication of EP1325331A1 publication Critical patent/EP1325331A1/de
Publication of EP1325331A4 publication Critical patent/EP1325331A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G01N33/56972—White blood cells
    • 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
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02—Separators
    • B03C5/022—Non-uniform field separators
    • B03C5/028—Non-uniform field separators using travelling electric fields, i.e. travelling wave dielectrophoresis [TWD]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00623—Immobilisation or binding
    • B01J2219/00626—Covalent
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00653—Making arrays on substantially continuous surfaces the compounds being bound to electrodes embedded in or on the solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00702—Processes involving means for analysing and characterising the products

Definitions

  • Magnetic forces refer to the forces acting on a particle due to the application of a magnetic field.
  • particles have to be magnetic or paramagnetic when sufficient magnetic forces are needed to manipulate particles.
  • a magnetic dipole ⁇ is induced in the particle
  • a “solution that selectively modifies red blood cells” is a solution that alters non- nucleated red blood cells such that they do not interfere with the dielectrophoretic separation of other cells or components of a blood sample, without substantially altering the integrity of white blood cells, or interfering with the ability of white blood cells to be dielectrically separated from other components of a blood sample.
  • microfabricated free-standing microstructures may include those described in "Design of asynchronous dielectric micromotors" by Hagedorn et al., in Journal of Electrostatics, Volume: 33, Pages 159-185 (1994).
  • Particles of complex compositions refer to the particles that comprise or consists of multiple compositional elements, for example, a metallic sphere covered with a thin layer of non-conducting polymer film..
  • a “nucleic acid molecule” is a polynucleotide.
  • a nucleic acid molecule can be DNA, RNA, or a combination of both.
  • a nucleic acid molecule can also include sugars other than ribose and deoxyribose incorporated into the backbone, and thus can be other than DNA or
  • the present invention recognizes that dielectrophoresis and traveling wave dielectrophoreses provide rapid, efficient and non-disruptive means for separating moieties in a sample.
  • the present invention also recognizes that it is often difficult to use dielectrophoresis and traveling wave dielectrophoresis to separate moieties from other components of a sample if different components of a sample have similar dielectric properties.
  • the modification of a dielectric property of one or more components of a sample need not be an absolute change in the response of a component to a given electric field pattern, but can also be a change, for example, in the rate of response of a component to a given electric field pattern.
  • a solution of the present invention can cause cell lysis or permeabilization by targeting cell membranes, including cell membrane proteins such as transporters and channels, and can compromise reagents such as salts, detergents, surfactants, lipids, sterols, polymers, alcohols, enzymes, ionophores, metabolic inhibitors, ion channel blockers and ion channel modifiers.
  • Cell lysis and cell permeabilization can change the charge density, net charge, or charge distribution of a cell.
  • a sample solution can also include compounds that alter the surface composition of sample components such as cells by altering the behavior or differentiation of the cells.
  • a sample solution can contain phytohemagglutinin and interleukin-2, compounds that stimulate T lymphocytes to increase the expression of MHC and co-stimulatory molecules on their surfaces, and lead to increased complexity in cell membrane morphology, and alter cell membrane permittivity (Huang et al., Biochimica Biophys. Acta 1417: 51-62 (1999)).
  • Sample solutions of the present invention can also change the net charge and charge distribution of a moiety by changing the internal compositions of non-homogeneous sample components such as cells.
  • a solution of the present invention can alter the internal composition of a nonhomogeneous sample component by introducing entities into the sample component, by removing entities from the internal portion of the component, or by causing chemical or morphological changes in the interior of the sample component.
  • Dielectrophoretic properties of components of samples mixed with a sample solution can be empirically tested to determine whether dielelctric properties of a sample component are altered by a sample solution.
  • electrorotation measurements can allow one skilled in the art to deduce dielectric properties of sample components. Measuring the rate of rotation of a moiety in a rotating electric field and derivation of dielectric properties from such measurements are demonstrated in Huang et al., Phys. Med. Biol. 37: 1499-1517 (1992); Huang et al, Phys. Med. Biol. 40: 1789-1806 (1995); Huang et al, Biochim. Biophys. Acta
  • a sample solution of the present invention when mixed with a sample, preferably makes a sample- sample solution mixtures that is of a conductivity that allows for the dielectric separation of one or more moieties in the sample. In most but not all cases, one skilled in the art can have an approximate idea of a desireable conductivity range for a sample solution-sample mixture.
  • a solution of the present invention preferably has a low osmolarity such that when added to a blood sample, the blood cells are in a hypotonic medium.
  • the final osmolarity is preferably between 20 mOsm and about 150 mOsm, most preferably between 30 mOsm and about 100 mOsm.
  • Suitable solutes for use in low osmolarity solutions of the present invention include glycerol, sugars such as sucrose, dextrose, and mannose, and sugar alcohols such as mannitol and sorbitol.
  • the chamber comprises electrodes
  • they will be incorporated onto or within the chip, but this is not a requirement of the present invention.
  • Electrodes on a chip can be of any shape, such as rectangular, castellated, triangular, circular, and the like. Electrodes can be arranged in various patterns, for example, spiral, parallel, interdigitated, polynomial, etc. Electrode arrays can be fabricated on a chip by microfabrication or micromachining methods known in the art, for example, electroplating, sputtering, photolithography or etching. Examples of a chip comprising electrodes include, but are not limited to, the dielectrophoresis electrode array on a glass substrate (e.g., Dielectrophoretic Manipulation of Particles by Wang et al., in IEEE Transaction on Industry Applications, Vol. 33, No.
  • a chamber that comprises a chip useable in the methods of the present invention can comprise one or more ports, or openings in the walls of a chamber.
  • a port is of a shape and size that allows a conduit to engage a port for the dispensing of a sample into the chamber.
  • a conduit can be any tube that allows for the entry of a fluid sample into the chamber.
  • Preferred conduits for use in the present invention include tubing, for example, rubber or polymeric tubing, e.g., tygon or teflon or PEEK tubing.
  • a port can provide an opening in a wall of a chamber for the dispensing of sample into the chamber by, for example, pipetting or inj ection.
  • a sample, a sample solution, and, optionally, additional solutions, buffers, preparations, or reagents can be added to a chamber by any convenient means, such as transfer with a pipet, injection with a syringe, gravity flow through a conduit, such as tygon tubing, etc.
  • a sample, a sample solution, and optionally other solutions, buffers, preparations, or reagents are added to a chamber in a continuous flow mode, in which a continuous stream of fluid is injected or pumped into at least one inlet port, and non-retained sample components and fluids exit the chamber via at least one outlet port, but this is not a requirement of the present invention
  • a sample solution of the present invention that selectively lyses red blood cells is added to a blood sample through a branched conduit.
  • the blood sample comprises white blood cells 120, red blood cells 100 and other blood sample components (not shown in Figure 1).
  • the blood sample-sample solution is directed to a chamber of the present invention that comprises a dielectrophoresis chip having an interdigitated parallel electrode array.
  • Application of a non-uniform electric field results in the retention of white blood cells 120 at electrode surfaces.
  • Red blood cell debris 140 and other blood sample components are flushed out of the chamber by fluid flow.
  • a moiety of interest 210 for example stem cells isolated from bone marrow, is modified by a sample solution of the present invention that comprises antibodies that bind cell surface antigens, and that alter the surface charge of the stem cells.
  • the sample comprise a number of other moieties such as progenitor and differentiated cells labeled as 220, 240, 260 and 280.
  • the sample solution-sample mixture can be preincubated for a period of time, for example, 5 to 60 minutes, before dispensing the sample solution-sample mixture by syring injection onto a chip comprising a spiral electrode array.
  • the altered stem cells 300 and other moieties are introduced together onto the chip.
  • a blood sample can be any blood sample, recently taken from a subject, taken from storage, or removed from a source external to a subject, such as clothing, upholstery, tools, etc.
  • a blood sample can therefore be an extract obtained, for example, by soaking an article containing blood in a buffer or solution.
  • a blood sample can be unprocessed, processed, or partially processed, for example, a blood sample that has been centrifuged to remove serum, dialyzed, subjected to flow cytometry, had reagents added to it, etc.
  • the processed blood sample may include buffy coat and cell samples separated by other methods such as flow cytometry, centrifugation density gradient, magnetic activated cell sorting.
  • a blood sample can be of any volume.
  • the chamber comprising electromagentic chip can be of any size or dimensions, and preferably can contain a fluid sample of between 0.001 microliter and 50 milliliters, more preferably between about 1 microliters and about 20 milliliters, and most preferably between about 10 microliters and about 10 milliliters.
  • a chamber can comprise any suitable material, for example, silicon, glass, metal, ceramics, polymers, plastics, etc. and can be of a rigid or flexible material. It is necessary to point out that for chambers with large volumes (up to 50 mL), chips of special geometries and configurations may have be used. The chips may be fabricated on flexible materials so that the chips can be folded to form tube like chambers. Multiple chips may be configured into a same chamber.
  • the electromagnetic elements may have to have certain configurations so that effective electromagnetic forces may be generated in the region of the interest in the chamber.
  • the embodiment depicted in Figure 5 includes a solution of the present invention that comprises magnetic microparticles 400 that comprise antibodies that specifically bind white blood cells.
  • the blood sample comrpises white blood cells 420 and red blood cells 450 and other cells and moieties (not shown in Figure 5).
  • the blood sample is mixed with the sample solution of the present invention to cause red blood cells being lysed.
  • the sample solution- sample mixture, together with a preparation of magnetic particles 400 is dispensed into a chamber.
  • the sample solution-sample mixture is incubated with the magnetic particles for a specified length of the time in the chamber, resulting the magnetic particles bound to white blood cells.
  • the chamber comprise an electromagnetic chip comprising microelectromagnetic units. Application of electric current to the micromagnetic units results in the capture of microparticles bound to white blood cells on the chip. Other sample components are washed away by pumping fluid through the chamber that comprises the electromagnetic chip.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Zoology (AREA)
  • Electrochemistry (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
EP01977391A 2000-10-09 2001-10-02 Zusammensetzungen und verfahren zur trennung von wirksamen anteilen auf chips Withdrawn EP1325331A4 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN00131649 2000-10-09
CNB001316494A CN100392384C (zh) 2000-10-09 2000-10-09 芯片上分离实体分子的方法和样品溶液
US686737 2000-10-10
US09/686,737 US6858439B1 (en) 1999-03-15 2000-10-10 Compositions and methods for separation of moieties on chips
PCT/US2001/030891 WO2002031506A1 (en) 2000-10-09 2001-10-02 Compositions and methods for separation of moieties on chips

Publications (2)

Publication Number Publication Date
EP1325331A1 EP1325331A1 (de) 2003-07-09
EP1325331A4 true EP1325331A4 (de) 2007-05-09

Family

ID=25739647

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01977391A Withdrawn EP1325331A4 (de) 2000-10-09 2001-10-02 Zusammensetzungen und verfahren zur trennung von wirksamen anteilen auf chips

Country Status (4)

Country Link
EP (1) EP1325331A4 (de)
AU (1) AU2001296516A1 (de)
CA (1) CA2424996A1 (de)
WO (1) WO2002031506A1 (de)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002211363A1 (en) * 2000-10-10 2002-04-22 Aviva Biosciences Corporation Individually addressable micro-electromagnetic unit array chips in horizontal configurations
EP1372828A4 (de) 2001-03-24 2008-10-29 Aviva Biosciences Corp Biochips mit ionentransporterfassungsstrukturen und verwendungsverfahren
US20060029955A1 (en) 2001-03-24 2006-02-09 Antonio Guia High-density ion transport measurement biochip devices and methods
EP2156879A3 (de) 2001-10-11 2010-07-07 Aviva Biosciences Corporation Verfahren, Zusammensetzungen und automatische Systeme zur Trennung von seltenen Zellen aus Flüssigkeitsproben
US8986944B2 (en) 2001-10-11 2015-03-24 Aviva Biosciences Corporation Methods and compositions for separating rare cells from fluid samples
US8980568B2 (en) 2001-10-11 2015-03-17 Aviva Biosciences Corporation Methods and compositions for detecting non-hematopoietic cells from a blood sample
US7166443B2 (en) 2001-10-11 2007-01-23 Aviva Biosciences Corporation Methods, compositions, and automated systems for separating rare cells from fluid samples
WO2003093494A2 (en) 2002-05-04 2003-11-13 Aviva Biosciences Corporation Apparatus including ion transport detecting structures and methods of use
EP1569510B1 (de) 2002-09-27 2011-11-02 The General Hospital Corporation Mikrofluidische vorrichtung zur zelltrennung und verwendungen davon
CN100338464C (zh) * 2002-12-27 2007-09-19 穆海东 一种蛋白质芯片载体的处理方法
US7156970B2 (en) 2003-06-12 2007-01-02 Palo Alto Research Center Incorporated Distributed multi-segmented reconfigurable traveling wave grids for separation of proteins in gel electrophoresis
ES2239886B1 (es) * 2003-11-05 2006-12-16 Universidad De Barcelona Metodo y aparato para la determinacion de la viabilidad celular.
US20070196820A1 (en) 2005-04-05 2007-08-23 Ravi Kapur Devices and methods for enrichment and alteration of cells and other particles
US8921102B2 (en) 2005-07-29 2014-12-30 Gpb Scientific, Llc Devices and methods for enrichment and alteration of circulating tumor cells and other particles
WO2007059194A1 (en) * 2005-11-15 2007-05-24 Massachusetts Institute Of Technology Iso-dielectric separation apparatus and methods of use
US20080050739A1 (en) 2006-06-14 2008-02-28 Roland Stoughton Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats
EP2029779A4 (de) 2006-06-14 2010-01-20 Living Microsystems Inc Verwendung hoch paralleler snp-genotypisierung zur fötalen diagnose
US8137912B2 (en) 2006-06-14 2012-03-20 The General Hospital Corporation Methods for the diagnosis of fetal abnormalities
US8372584B2 (en) 2006-06-14 2013-02-12 The General Hospital Corporation Rare cell analysis using sample splitting and DNA tags
CA2657621A1 (en) 2006-07-14 2008-01-17 Aviva Biosciences Corporation Methods and compositions for detecting rare cells from a biological sample
WO2010033578A2 (en) 2008-09-20 2010-03-25 The Board Of Trustees Of The Leland Stanford Junior University Noninvasive diagnosis of fetal aneuploidy by sequencing
EP4253937A3 (de) 2014-02-26 2023-11-08 Brigham and Women's Hospital, Inc. Verfahren zur zelllevetation und -überwachung
CN108970403A (zh) * 2018-08-20 2018-12-11 重庆医科大学 一种基于介电电泳的巨型脂质体制备及分选结构和方法
EP4089395A1 (de) * 2021-05-11 2022-11-16 Ceidos SA Zellkulturüberwachungssystem
JP7714685B2 (ja) * 2021-05-11 2025-07-29 セイドス・エスア 細胞培養監視システム及び誘電泳動カートリッジ

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHENG J ET AL: "Preparation and hybridization analysis of DNA/RNA from E. coli on microfabricated bioelectronic chips.", NATURE BIOTECHNOLOGY JUN 1998, vol. 16, no. 6, June 1998 (1998-06-01), pages 541 - 546, XP002427046, ISSN: 1087-0156 *
PETHIG R ET AL: "Applications of dielectrophoresis in biotechnology.", TRENDS IN BIOTECHNOLOGY OCT 1997, vol. 15, no. 10, October 1997 (1997-10-01), pages 426 - 432, XP002427047, ISSN: 0167-7799 *
PLAVINS J AND LAUVA M, JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS, vol. 122, 1993, pages 349 - 353, XP002427048 *
See also references of WO0231506A1 *

Also Published As

Publication number Publication date
AU2001296516A1 (en) 2002-04-22
WO2002031506A1 (en) 2002-04-18
EP1325331A1 (de) 2003-07-09
CA2424996A1 (en) 2002-04-18

Similar Documents

Publication Publication Date Title
US6858439B1 (en) Compositions and methods for separation of moieties on chips
EP1325331A1 (de) Zusammensetzungen und verfahren zur trennung von wirksamen anteilen auf chips
Gascoyne et al. Dielectrophoresis-based sample handling in general-purpose programmable diagnostic instruments
US20020076825A1 (en) Integrated biochip system for sample preparation and analysis
Lapizco‐Encinas et al. Dielectrophoresis for the manipulation of nanobioparticles
US7081192B1 (en) Methods for manipulating moieties in microfluidic systems
US7968305B2 (en) Biochips including ion transport detecting structures and methods of use
US7988841B2 (en) Treatment of biological samples using dielectrophoresis
US8932447B2 (en) Ex-vivo multi-dimensional system for the separation and isolation of cells, vesicles, nanoparticles, and biomarkers
Pethig Dielectrophoresis: using inhomogeneous AC electrical fields to separate and manipulate cells
EP2150350B1 (de) Integrierte fluidische vorrichtungen mit magnetischer sortierung
US7658829B2 (en) Integrated microfluidic transport and sorting system
US20060228749A1 (en) Methods for manipulating moieties in microfluidic systems
JP2004503775A (ja) 検体混合物の組み合わせた磁気泳動および誘電泳動の操作のための方法および装置
Kentsch et al. Microdevices for separation, accumulation, and analysis of biological micro-and nanoparticles
US20230001415A1 (en) Method and Apparatus for Isolating and Detecting Biological and Other Particles
CN100392384C (zh) 芯片上分离实体分子的方法和样品溶液
WO2007059194A1 (en) Iso-dielectric separation apparatus and methods of use
Cemazar et al. Electrical manipulation and sorting of cells
Vykoukal et al. A combined dielectrophoretic and field-flow fractionation microsystem for biomedical separation and analysis
Roy et al. Enhancing the Performance of Surface-Based Biosensors by AC Electrokinetic Effects—A Review
Li et al. BioMEMS for Cellular Manipulation and Analysis

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20030404

AK Designated contracting states

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

A4 Supplementary search report drawn up and despatched

Effective date: 20070411

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20070613