Microfluidic device for cell separation and uses thereof
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A01N-001/02
C07K-001/00
C12N-005/00
C12N-005/02
C12N-005/071
G01N-033/569
G01N-033/50
B82Y-030/00
G01N-033/574
B01L-003/00
B01L-009/00
G01N-033/543
G01N-001/40
출원번호
US-0529453
(2003-09-29)
등록번호
US-8895298
(2014-11-25)
국제출원번호
PCT/US03/30965
(2003-09-29)
§371/§102 date
20051219
(20051219)
국제공개번호
WO2004/029221
(2004-04-08)
발명자
/ 주소
Toner, Mehmet
Truskey, George
Kapur, Ravi
출원인 / 주소
The General Hospital Corporation
대리인 / 주소
Fish & Richardson P.C.
인용정보
피인용 횟수 :
6인용 특허 :
290
초록▼
The invention features methods for separating cells from a sample (e.g., separating fetal red blood cells from maternal blood). The method begins with the introduction of a sample including cells into one or more microfluidic channels. In one embodiment, the device includes at least two processing s
The invention features methods for separating cells from a sample (e.g., separating fetal red blood cells from maternal blood). The method begins with the introduction of a sample including cells into one or more microfluidic channels. In one embodiment, the device includes at least two processing steps. For example, a mixture of cells is introduced into a microfluidic channel that selectively allows the passage of a desired type of cell, and the population of cells enriched in the desired type is then introduced into a second microfluidic channel that allows the passage of the desired cell to produce a population of cells further enriched in the desired type. The selection of cells is based on a property of the cells in the mixture, for example, size, shape, deformability, surface characteristics (e.g., cell surface receptors or antigens and membrane permeability), or intracellular properties (e.g., expression of a particular enzyme).
대표청구항▼
1. A method of producing a cell population enriched in a first type of cell larger than an adult, enucleated red blood cell, said method comprising: continuously flowing a blood sample of a specific volume through a channel in a microfluidic device comprising;(i) continuously flowing the blood sampl
1. A method of producing a cell population enriched in a first type of cell larger than an adult, enucleated red blood cell, said method comprising: continuously flowing a blood sample of a specific volume through a channel in a microfluidic device comprising;(i) continuously flowing the blood sample past a series of obstacles in the channel, the obstacles fixed in position separated by gaps arranged so that flow of the blood sample past the obstacles directs adult, enucleated red blood cells and cells smaller than adult, enucleated red blood cells in a first direction and directs cells larger than adult, enucleated red blood cells in a second direction to produce a first sample enriched in cells larger than adult, enucleated red blood cells; and without stopping the flow of the first sample,(ii) continuously flowing the first sample past obstacles that each comprise one or more binding moieties that preferentially bind to the first type of cell in the first sample, thereby producing a population enriched in the first cell type. 2. The method of claim 1, further comprising prior to, during, or after steps (i) and (ii) contacting said sample with a solution that preferentially lyses cells of a second type, to cause greater lysis of cells of the second type compared to cells of the first type. 3. The method of claim 1, further comprising after steps (i) and (ii) collecting one or more cells of said first type. 4. The method of claim 2, wherein said solution comprises NaHCO3 and acetazolamide. 5. The method of claim 2, further comprising the step, after said lysis, of diluting the product of said lysis with a diluent. 6. The method of claim 1, wherein said binding moiety comprises an anti-CD71, an anti-CD36, an anti-GPA, or an anti-CD45 antibody, or a combination thereof. 7. The method of claim 1, wherein said first type of cell is a fetal red blood cell. 8. The method of claim 1, wherein at least 60% of cells of said first type in said sample are bound to said obstacles of step (ii). 9. The method of claim 1, wherein said obstacles of step (ii) are ordered in a two-dimensional array. 10. The method of claim 1 further comprising after step (ii) releasing cells bound to said obstacles. 11. The method of claim 10, wherein said releasing comprises applying a shear force or lysing said bound cells. 12. The method of claim 10, further comprising analyzing the cellular contents of said cells after said releasing. 13. The method of claim 12, wherein said analyzing comprises Fluorescence In Situ Hybridization (FISH). 14. The method of claim 12, wherein said analyzing comprises nucleic acid analysis. 15. The method of claim 1, wherein said first type of cell comprises fetal cells, epithelial cells, tumor cells, stem cells, bacteria, protozoa, or fungi. 16. The method of claim 10, further comprising identifying one or more cells of said first type after said releasing. 17. The method of claim 10, wherein said binding moiety comprises an antibody. 18. The method of claim 17, wherein said antibody is a fetal-cell specific, epithelial-cell specific, tumor-cell specific, stem-cell specific, bacteria specific, protozoan specific, or fungal specific antibody. 19. The method of claim 1 further comprising staining cells bound to said obstacles of step (ii) to identify cells bound thereto. 20. The method of claim 19, further comprising analyzing the cellular contents of said cells during or after said staining. 21. The method of claim 20, wherein said analyzing comprises nucleic acid analysis. 22. The method of claim 19, wherein said staining comprises Fluorescence In Situ Hybridization (FISH). 23. The method of claim 19, wherein said first type of cell comprises fetal cells, epithelial cells, or tumor cells. 24. The method of claim 19, further comprising identifying one or more cells of said first type during or after said staining. 25. The method of claim 19, wherein said binding moiety comprises an antibody. 26. The method of claim 25, wherein said antibody is a fetal-cell specific, epithelial-cell specific, tumor-cell specific, stem-cell specific, bacteria specific, protozoan specific, or fungal specific antibody.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (290)
Soane David S. ; Soane Zoya M., Acrylic microchannels and their use in electrophoretic applications.
Sheppard ; Jr. Norman F. ; Mian Alec ; Kellogg Gregory ; Kieffer-Higgins Stephen G. ; Carvalho Bruce L., Affinity binding-based system for detecting particulates in a fluid.
Sheppard ; Jr. Norman F. ; Mian Alec ; Kellogg Gregory ; Kieffer-Higgins Stephen G. ; Carvalho Bruce L., Affinity binding-based system for detecting particulates in a fluid.
Terstappen Leon W. M. M. (Huntingdon Valley PA) Rao Galla C. (Princeton NJ) Gohel Dhanesh I. (Levittown PA) Feeley Brian P. (Easton PA) Gross Steven (Ambler PA) Church Ellen S. (Trenton NJ) Liberti P, Affinity-binding separation and release of one or more selected subset of biological entities from a mixed population th.
Asgari Morteza ; Blick Mark ; Bresser Joel ; Cubbage Michael Lee ; Prashad Nagindra, Amplification of mRNA for distinguishing fetal cells in maternal blood.
Minshall Billy W. (Mill Creek WA) Maloney Patrick M. (Bothell WA) Mill Fred (Bothell WA) Heimfeld Shelly (Woodinville WA) Corpuz Stanley (Kirkland WA) Thompson Penny (Snohomish WA) Peterson Eric (Sea, Apparatus and method for particle separation in a closed field.
Liberti Paul A. (Churchville PA) Wang Yuzhou (Wayne PA) Tang Weixin (Devon PA) Feeley Brian P. (Easton PA) Gohel Dhanesh I. (Philadelphia PA), Apparatus and methods for magnetic separation featuring external magnetic means.
Goffe Randal A. (Bothell WA) Blat George (Edmonds WA) Emde Michael D. (Redmond WA) Mill Fred (Bothell WA) Maloney Patrick M. (Bothell WA), Apparatus for cell separation.
Liberti Paul A. (Churchville PA) Feeley Brian P. (Easton PA) Gohel Dhanesh I. (Philadelphia PA), Apparatus for magnetic separation featuring external magnetic means.
McBride Sterling Eduard ; Cherukuri Satyam Choudary ; Kumar Rajan ; Ladd Judith Ann ; Fan Zhonghui Hugh ; Bentz Bryan Lloyd ; Zanzucchi Peter J., Apparatus for separating molecules.
Hillman Robert S. (Cupertino CA) Cobb Michael E. (Sunnyvale CA) Allen Jimmy D. (Los Altos CA) Gibbons Ian (Menlo Park CA) Ostoich Vladimir E. (San Jose CA) Winfrey Laura J. (Belmont CA), Capillary flow device.
Hillman Robert S. (Cupertino CA) Cobb Michael E. (Sunnyvale CA) Allen Jimmy D. (Los Altos CA) Gibbons Ian (Menlo Park CA) Ostoich Vladimir E. (San Jose CA) Winfrey Laura J. (Belmont CA), Capillary flow device.
Tanaka Shinji (Akishima JPX) Sato Kazuo (Tokyo JPX) Terasawa Tsuneo (Hachioji JPX) Kawamura Yoshio (Kokubunji JPX) Tsuruoka Hisashi (Hachioji JPX), Chamber plate for use in cell fusion and a process for production thereof.
Cheng Jing ; Sheldon ; III Edward L. ; Wu Lei ; O'Connell James P., Channel-less separation of bioparticles on a bioelectronic chip by dielectrophoresis.
Liberti Paul A. ; Rao Galla C. ; Chiarappa Joseph N., Coated, resuspendable magnetically responsive, transition metal oxide particles and method for the preparation thereof.
Pourahmadi, Farzad; McMillan, William A.; Ching, Jesus; Chang, Ronald; Christel, Lee A.; Kovacs, Gregory T. A.; Northrup, M. Allen; Petersen, Kurt E., Device incorporating a microfluidic chip for separating analyte from a sample.
Hansmann Douglas D. ; Grace John P. ; Lowery Michael G. ; Oosta Gary M. ; Loomis Neil W. ; Shain Eric B. ; Schapira Thomas G., Devices and methods utilizing arrays of structures for analyte capture.
Hansmann Douglas D. ; Grace John P. ; Lowery Michael G. ; Oosta Gary M. ; Loomis Neil W. ; Shain Eric B. ; Schapira Thomas G., Devices and methods utilizing arrays of structures for analyte capture.
Ozkan, Mihrimah; Esener, Sadik; Bhatia, Sangeeta, Electric-field-assisted fluidic assembly of inorganic and organic materials, molecules and like small things including living cells.
Asgari Morteza (Houston TX) Blick Mark (Houston TX) Bresser Joel (Bellaire TX) Cubbage Michael L. (Houston TX) Prashad Nagindra (Houston TX), Enriching and identifying fetal cells in maternal blood for in situ hybridization.
Asgari Morteza ; Blick Mark ; Bresser Joel ; Cubbage Michael Lee ; Prashad Nagindra, Enriching and identifying fetal cells in maternal blood for in situ hybridization on a solid surface.
Kbler Ulrich (Munich DEX) Hoffman Rainer (Frstenfeldbruck DEX), Extraction and cultivation of transformed cells and production of antibodies directed against them.
Graham Marshall D. (Framingham MA) Graham William G. (Lexington KY), Flux diverting flow chamber for high gradient magnetic separation of particles from a liquid medium.
Wada, H. Garrett; Kopf-Sill, Anne R.; Alajoki, Marja Liisa; Parce, J. Wallace; Wang, Benjamin N.; Chow, Andrea W.; Dubrow, Robert S., Focusing of microparticles in microfluidic systems.
Iida, Kazuhiro; Kawaura, Hisao; Baba, Masakazu; Sakamoto, Toshitsugu; Sano, Toru; Iguchi, Noriyuki, Fractionating apparatus having colonies of pillars arranged in migration passage at interval and process for fabricating pillars.
Briggs Donald David ; Chary Srikanth Ranga ; Jen Shang-Chih David ; Schwartz Richard Merrill, High gradient magnetic device and method for cell separation or purification.
Agrawal,Anoop; Cronin,John P.; Tonazzi,Juan C.; Goodyear,A. G.; LeCompte,Robert S.; Hogan,Michael E.; Galbraith,David W., High surface area substrates for microarrays and methods to make same.
Ravkin Ilya, Identification of objects of interest using multiple illumination schemes and finding overlap of features in corresponding multiple images.
Liberti Paul A. (Churchville PA), Immunoassay system and procedure based on precipitin-like interaction between immune complex and Clq or other non-immuno.
Baust John M. ; Van Buskirk Robert G. ; Baust John G. ; Aby Mathew, Inclusion of apoptotic regulators in solutions for cell storage at low temperature.
Moon, James E.; Davis, Timothy J.; Galvin, Gregory J.; Schultz, Gary A.; Corso, Thomas N.; Lowes, Stephen, Integrated monolithic microfabricated electrospray and liquid chromatography system and method.
Asgari Morteza ; Blick Mark ; Bresser Joel ; Cubbage Michael Lee ; Prashad Nagindra, Intracellular antigens for identifying fetal cells in maternal blood.
Mehta, Tammy Burd; Kopf-Sill, Anne R.; Parce, J. Wallace; Chow, Andrea W.; Bousse, Luc J.; Knapp, Michael R.; Nikiforov, Theo T.; Gallagher, Steve, Manipulation of microparticles in microfluidic systems.
Luderer Albert A. (Corning NY) Odstrchel Gerald (Horseheads NY) Zine ; Jr. Anthony R. (Corning NY), Means for separating lymphocytes and monocytes from anticoagulated blood.
Zld Tibor (Philippistrasse 13 4400 Mnster DEX), Method and apparatus for fast, reliable, and environmentally safe dispensing of fluids, gases and individual particles o.
Huang, Lotien Richard; Sturm, James Christopher; Austin, Robert Hamilton, Method and apparatus for generating electric fields and flow distributions for rapidly separating molecules.
Kedar Haim ; Sugarman Jeffrey H. ; Binnie Alastair A.,GBX ; Barrett Ronald W. ; Chan Sam ; Martin Edith Lo, Method and apparatus for transferring and combining reagents.
Ceriani Roberto L. (1089 Via Roble Lafayette CA 94549) Peterson Jerry A. (5916 Chabot Rd. Oakland CA 94618), Method and compositions for carcinoma diagnosis.
Fodstad .O slashed.ystein,NOX ; H.o slashed.if.o slashed.dt Hanne Kleppe,NOX ; Rye Philip,NOX, Method and device for detection of specific target cells in specialized or mixed cell populations and solutions containing mixed cell populations.
J. Michael Ramsey ; Robert S. Foote, Method for analyzing nucleic acids by means of a substrate having a microchannel structure containing immobilized nucleic acid probes.
Fodstad .O slashed.ystein,NOX ; Kvalheim Gunnar,NOX, Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations.
Fodstad, Øystein; Kvalheim, Gunnar, Method for detection of specific target cells in specialized or mixed cell population and solutions containing mixed cell populations.
Sammons David W. (Tucson AZ) Manley Michael (Tucson AZ) Utermohlen Joseph G. (Tucson AZ) Twitty Garland E. (Tucson AZ), Method for enrichment of fetal cell population from maternal whole blood samples.
Drouin Regen,CAX ; Forest Jean-Claude,CAX ; Masse Jacques,CAX, Method for enrichment of fetal cells from maternal blood and use of same in determination of fetal sex and detection of chromosomal abnormalities.
Wang Yuzhou (Wayne PA) Tang Weixin (Landsdale PA) Cronin William J. (Matawan NJ) Liberti Paul A. (Huntingdon Valley PA), Method for magnetic separation featuring magnetic particles in a multi-phase system.
Gravenstein Dietrich (Gainesville FL) Beneken J. E. W. (Helmond FL NLX) Lampotang Samsun (Gainesville FL) Gravenstein Nikolaus (Gainesville FL) Brooks Michael A. (Gainesville FL) Gibby Gordon L. (Gai, Method for noninvasive intermittent and/or continuous hemoglobin, arterial oxygen content, and hematocrit determination.
Saunders Alexander M. (San Carlos CA) Zarowitz Michael A. M. (San Carlos CA) Baldwin Patricia J. (Sunnyvale CA), Method for separating rare cells from a population of cells.
Sammons David W. (Tucson AZ) Twitty Garland E. (Tucson AZ) Utermohlen Joseph G. (Tucson AZ) Sharnez Rizwan (Sicklerville NJ), Method for separation of nucleated fetal erythrocytes from maternal blood samples.
Rimm David L. ; Levine Robert A. ; Wardlaw Stephen C. ; Fiedler Paul, Method for the detection, identification, enumeration and confirmation of circulating cancer and/or hematologic progenitor cells in whole blood.
Coster Hans (New South Wales AU) Pilwat Gunter (Julich DT) Zimmermann Ulrich (Julich DT), Method of and device for measuring elastic and di-electric properties of the diaphragm of living cells.
Wilding Peter (Paoli PA) Kricka Larry J. (Berwyn PA) Zemel Jay N. (Jenkintown PA), Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems.
Leon W. M. M. Terstappen ; Galla Chandra Rao ; Jonathan W. Uhr ; Emilian V. Racila ; Paul A. Liberti, Methods and reagents for the rapid and efficient isolation of circulating cancer cells.
Terstappen, Leon W. M. M.; Rao, Galla Chandra; Uhr, Jonathan W.; Racila, Emilian V.; Liberti, Paul A., Methods and reagents for the rapid and efficient isolation of circulating cancer cells.
Terstappen Leon W. M. M. ; Liberti Paul A., Methods for biological substance analysis employing internal magnetic gradients separation and an externally-applied transport force.
Bittner Michael L. ; Morrison Larry E. ; Legator Mona S., Methods for multiple direct label probe detection of multiple chromosomes or regions thereof by in situ hybridization.
Bittner, Michael L.; Morrison, Larry E.; Legator, Mona S., Methods for multiple direct label probe detection of multiple chromosomes or regions thereof by in situ hybridization.
Roche Patrick C. ; Klee George G. ; Limburg Paul J. ; Ahlquist David A., Methods of recovering colorectal epithelial cells or fragments thereof from stool.
Jacobson Stephen C. ; Ramsey J. Michael, Microfabricated device and method for multiplexed electrokinetic focusing of fluid streams and a transport cytometry method using same.
Bernhard H. Weigl ; Paul Yager ; James P. Brody ; Mark R. Holl ; Fred K. Forster ; Eric Altendorf ; Paul C. Galambos ; Margaret Kenny ; David Schutte ; Gregory Hixson ; Diane Zebert ; Andr, Microfabricated devices and methods.
Jacobson Stephen C. ; Ramsey J. Michael, MicrofluIdic circuit designs for performing electrokinetic manipulations that reduce the number of voltage sources and fluid reservoirs.
Nelson, Robert J.; Hooper, Herbert H.; Hauser, Alan K.; Singh, Sharat; Williams, Stephen J.; Sassi, Alexander P., Microfluidic apparatus and method for purification and processing.
Jacobson Stephen C. ; Ramsey J. Michael, Microfluidic circuit designs for performing fluidic manipulations that reduce the number of pumping sources and fluid reservoirs.
Nelson Robert J. ; Hooper Herbert H. ; Hauser Alan K. ; Singh Sharat ; Williams Stephen J. ; Sassi Alexander P., Microfluidic method for nucleic acid purification and processing.
Robert J. Nelson ; Herbert H. Hooper ; Alan K. Hauser ; Sharat Singh ; Stephen J. Williams ; Alexander P. Sassi, Microfluidic method for nucleic acid purification and processing.
Culbertson, Christopher T.; Jacobson, Stephen C.; McClain, Maxine A.; Ramsey, J. Michael, Microfluidic systems and methods of transport and lysis of cells and analysis of cell lysate.
Austin Robert H. (Princeton NJ) Volkmuth Wayne D. (Menlo Park MN) Rathburn Lynn C. (Ithaca NY), Microlithographic array for macromolecule and cell fractionation.
Lee Allan Christel ; Gregory T. A. Kovacs ; William A. McMillan ; M. Allen Northrup ; Kurt E. Petersen ; Farzad Pourahmadi, Non-planar microstructures for manipulation of fluid samples.
Goldberg Seth (630 First Avenue (Apt. 14J) New York NY 10016) Logan Jonothan L. (Birch Hill Rd. ; R.D. 1 ; Box 2480 Westford VT 05494), Noninvasive fetal oxygen monitor using NMR.
Hollis Mark A. ; Ehrlich Daniel J. ; Murphy R. Allen ; Kosicki Bernard B. ; Rathman Dennis D. ; Mathews Richard H. ; Burke Barry E. ; Eggers Mitch D. ; Hogan Michael E. ; Varma Rajender Singh, Optical and electrical methods and apparatus for molecule detection.
Niimura Toshinobu (Mineola NY) Takahashi Tadashi (Port Washington NY) Kashiba Mutsuro (Williston Park NY) Sakai Ko (Hew Hyde Park NY) Kano Tokio (Bellerose NY), Plate substrate immunoassay device and method for performing a multi-test immunoassay on a specimen.
Mullis Kary B. (La Jolla CA) Erlich Henry A. (Oakland CA) Arnheim Norman (Woodland Hills CA) Horn Glenn T. (Emeryville CA) Saiki Randall K. (Richmond CA) Scharf Stephen J. (Berkeley CA), Process for amplifying, detecting, and/or cloning nucleic acid sequences.
Giddings John C. (Salt Lake City UT), Process for continuous particle and polymer separation in split-flow thin cells using flow-dependent lift forces.
Sammons David W. ; Manley Michael ; Utermohlen Joseph G. ; Twitty Garland E., System and method for enrichment of rare cell population from whole blood samples.
Pall David B. (Roslyn Estates NY) Gsell Thomas C. (Glen Cove NY) Matkovich Vlado I. (Glen Cove NY) Bormann Thomas (Seaford NY), System for processing biological fluid.
Sammons David W. ; Twitty Garland E. ; Utermohlen Joseph G. ; Sharnez Rizwan, System for separation of nucleated fetal erythrocytes from maternal blood samples.
Teng Nelson N. H. (Hillsborough CA) Bhat Neelima M. (Cupertino CA) Bieber Marcia M. (Los Altos Hills CA), Triple gradient process for recovering nucleated fetal cells from maternal blood.
Teng Nelson N. H. (Millsborough CA) Bieber Marcia (Los Altos Hills CA) Bhat Neelima M. (Cupertino CA), Triple gradient process with antibody panning to recover nucleated fetal cells from maternal blood.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.