ATE441857T1 - Verfahren und zusammensetzungen zum nachweis des aktivierungszustands multipler proteine in einzelzellen - Google Patents

Verfahren und zusammensetzungen zum nachweis des aktivierungszustands multipler proteine in einzelzellen

Info

Publication number
ATE441857T1
ATE441857T1 AT02805693T AT02805693T ATE441857T1 AT E441857 T1 ATE441857 T1 AT E441857T1 AT 02805693 T AT02805693 T AT 02805693T AT 02805693 T AT02805693 T AT 02805693T AT E441857 T1 ATE441857 T1 AT E441857T1
Authority
AT
Austria
Prior art keywords
compositions
methods
detecting
activation state
individual cells
Prior art date
Application number
AT02805693T
Other languages
English (en)
Inventor
Omar Perez
Garry Nolan
Original Assignee
Univ Leland Stanford Junior
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27737231&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ATE441857(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Univ Leland Stanford Junior filed Critical Univ Leland Stanford Junior
Application granted granted Critical
Publication of ATE441857T1 publication Critical patent/ATE441857T1/de

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
    • C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • G01N33/5041—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects involving analysis of members of signalling pathways
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5094—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for blood cell populations
    • 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
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • 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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • 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
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • 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
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
    • G01N2021/6441—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks with two or more labels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G01N2333/91205—Phosphotransferases in general
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
    • G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
    • G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
    • G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
    • G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
    • G01N2333/96466—Cysteine endopeptidases (3.4.22)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2405/00—Assays, e.g. immunoassays or enzyme assays, involving lipids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2440/00—Post-translational modifications [PTMs] in chemical analysis of biological material
    • G01N2440/14—Post-translational modifications [PTMs] in chemical analysis of biological material phosphorylation
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/973—Simultaneous determination of more than one analyte
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y10T436/101666—Particle count or volume standard or control [e.g., platelet count standards, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
AT02805693T 2001-07-10 2002-07-10 Verfahren und zusammensetzungen zum nachweis des aktivierungszustands multipler proteine in einzelzellen ATE441857T1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US30443401P 2001-07-10 2001-07-10
US31014101P 2001-08-02 2001-08-02
PCT/US2002/022328 WO2003067210A2 (en) 2001-07-10 2002-07-10 Methods and compositions for detecting the activation state of the multiple proteins in single cells

Publications (1)

Publication Number Publication Date
ATE441857T1 true ATE441857T1 (de) 2009-09-15

Family

ID=27737231

Family Applications (1)

Application Number Title Priority Date Filing Date
AT02805693T ATE441857T1 (de) 2001-07-10 2002-07-10 Verfahren und zusammensetzungen zum nachweis des aktivierungszustands multipler proteine in einzelzellen

Country Status (7)

Country Link
US (6) US7563584B2 (de)
EP (1) EP1415156B1 (de)
JP (1) JP4401172B2 (de)
AT (1) ATE441857T1 (de)
AU (1) AU2002365421A1 (de)
DE (1) DE60233574D1 (de)
WO (1) WO2003067210A2 (de)

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090118139A1 (en) * 2000-11-07 2009-05-07 Caliper Life Sciences, Inc. Microfluidic method and system for enzyme inhibition activity screening
US7393656B2 (en) * 2001-07-10 2008-07-01 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for risk stratification
WO2003067210A2 (en) * 2001-07-10 2003-08-14 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for detecting the activation state of the multiple proteins in single cells
US7695926B2 (en) 2001-07-10 2010-04-13 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for detecting receptor-ligand interactions in single cells
US7381535B2 (en) * 2002-07-10 2008-06-03 The Board Of Trustees Of The Leland Stanford Junior Methods and compositions for detecting receptor-ligand interactions in single cells
US20040197836A1 (en) * 2003-04-04 2004-10-07 Hashemi Brian B. Measurement of F-actin in whole blood cellular subsets
EP2371835A1 (de) * 2003-07-03 2011-10-05 The Trustees Of The University Of Pennsylvania Inhibition der Syk-Kinaseexpression
WO2006017549A2 (en) * 2004-08-03 2006-02-16 Vertex Pharmaceuticals Incoporated Cell-based kinase assay
WO2006079092A2 (en) * 2005-01-24 2006-07-27 The Board Of Trustees Of The Leland Stanford Junior University Method for modeling cell signaling systems by means of bayesian networks
US8214157B2 (en) 2006-03-31 2012-07-03 Nodality, Inc. Method and apparatus for representing multidimensional data
AU2007277050A1 (en) * 2006-07-28 2008-01-31 The Research Foundation Of State University Of New York Methods and kits for measurement of lymphocyte function
US20090098594A1 (en) * 2007-08-21 2009-04-16 Nodality, Inc. Methods for diagnosis prognosis and methods of treatment
EP2214824A4 (de) * 2007-11-28 2015-08-19 Smart Tube Inc Vorrichtungen, systeme und verfahren zur entnahme, stimulation, stabilisierung und analyse einer biologischen probe
US20090269800A1 (en) * 2008-04-29 2009-10-29 Todd Covey Device and method for processing cell samples
US20090269773A1 (en) * 2008-04-29 2009-10-29 Nodality, Inc. A Delaware Corporation Methods of determining the health status of an individual
US20090291458A1 (en) * 2008-05-22 2009-11-26 Nodality, Inc. Method for Determining the Status of an Individual
GB2474613A (en) * 2008-07-10 2011-04-20 Nodality Inc Methods and apparatus related to management of experiments
US9183237B2 (en) 2008-07-10 2015-11-10 Nodality, Inc. Methods and apparatus related to gate boundaries within a data space
EP2304436A1 (de) 2008-07-10 2011-04-06 Nodality, Inc. Diagnose-, prognose- und behandlungsverfahren
US8399206B2 (en) 2008-07-10 2013-03-19 Nodality, Inc. Methods for diagnosis, prognosis and methods of treatment
US20100030719A1 (en) * 2008-07-10 2010-02-04 Covey Todd M Methods and apparatus related to bioinformatics data analysis
US20100014741A1 (en) * 2008-07-10 2010-01-21 Banville Steven C Methods and apparatus related to gate boundaries within a data space
EP2318836B1 (de) * 2008-09-04 2013-07-31 Beckman Coulter, Inc. Pan-kinase-aktivierung und evaluierung von signalpfaden
ES2763537T3 (es) * 2008-09-16 2020-05-29 Beckman Coulter Inc Diagrama de árbol interactivo para datos de citometría de flujo
WO2010045651A1 (en) * 2008-10-17 2010-04-22 Nodality, Inc. Methods for analyzing drug response
US9034257B2 (en) * 2008-10-27 2015-05-19 Nodality, Inc. High throughput flow cytometry system and method
US8309306B2 (en) 2008-11-12 2012-11-13 Nodality, Inc. Detection composition
US20100209929A1 (en) * 2009-01-14 2010-08-19 Nodality, Inc., A Delaware Corporation Multiple mechanisms for modulation of jak/stat activity
US20100204973A1 (en) * 2009-01-15 2010-08-12 Nodality, Inc., A Delaware Corporation Methods For Diagnosis, Prognosis And Treatment
US20100233733A1 (en) * 2009-02-10 2010-09-16 Nodality, Inc., A Delaware Corporation Multiple mechanisms for modulation of the pi3 kinase pathway
US20100215644A1 (en) * 2009-02-25 2010-08-26 Nodality, Inc. A Delaware Corporation Analysis of nodes in cellular pathways
EP2409138B1 (de) * 2009-03-16 2017-08-02 Clondiag GmbH Fluoreszenznachweistests auf mikrofluidischen vorrichtungen
US8242248B2 (en) * 2009-03-23 2012-08-14 Nodality, Inc. Kits for multiparametric phospho analysis
US8187885B2 (en) * 2009-05-07 2012-05-29 Nodality, Inc. Microbead kit and method for quantitative calibration and performance monitoring of a fluorescence instrument
US20100297676A1 (en) * 2009-05-20 2010-11-25 Nodality, Inc. Methods for diagnosis, prognosis and methods of treatment
US9459246B2 (en) 2009-09-08 2016-10-04 Nodality, Inc. Induced intercellular communication
EP2476053A4 (de) * 2009-09-08 2014-03-12 Nodality Inc Analyse von zellnetzwerken
CA2805247C (en) 2010-07-14 2021-08-10 The Curators Of The University Of Missouri Nanopore-facilitated single molecule detection of nucleic acids
US8956859B1 (en) 2010-08-13 2015-02-17 Aviex Technologies Llc Compositions and methods for determining successful immunization by one or more vaccines
US8734859B1 (en) 2010-11-13 2014-05-27 Sirbal Ltd. Molecular combinations for cancer or other disease treatment
US8541382B2 (en) 2010-11-13 2013-09-24 Sirbal Ltd. Cardiac glycoside analogs in combination with emodin for cancer therapy
US9095606B1 (en) 2010-11-13 2015-08-04 Sirbal Ltd. Molecular and herbal combinations for treating psoriasis
US9066974B1 (en) 2010-11-13 2015-06-30 Sirbal Ltd. Molecular and herbal combinations for treating psoriasis
US9005909B2 (en) * 2011-01-06 2015-04-14 Rigel Pharmaceuticals, Inc. Whole blood assay for measuring AMPK activation
JP5862671B2 (ja) * 2011-08-23 2016-02-16 日本電気株式会社 情報処理システム、情報処理方法、情報処理装置およびその制御方法と制御プログラム
EP2753924B1 (de) * 2011-09-06 2022-10-26 Becton Dickinson and Company Verfahren und zusammensetzungen zur zytometrischen detektion von zirkulierenden tumorzellen in einer probe
CA2851828A1 (en) 2011-10-28 2013-05-02 Presage Biosciences, Inc. Methods for drug delivery
EP2623978A1 (de) * 2012-02-03 2013-08-07 Charité - Universitätsmedizin Berlin CD8+ T-Zell-Subpopulationen als Indikator zur Vorhersage von verzögerter Bruchheilung
WO2013188756A1 (en) * 2012-06-15 2013-12-19 The University Of Chicago Oligonucleotide-mediated quantitative multiplexed immunoassays
TWI794644B (zh) 2012-12-17 2023-03-01 美商奇諾麥提卡公司 用於增加甲醇存在下之還原當量可利用性及用於製造與其相關己二酸、6-胺基己酸、己二胺或己內醯胺之微生物及方法
AU2014227754B2 (en) 2013-03-15 2018-03-01 The Curators Of The University Of Missouri Encoded nanopore sensor for multiplex nucleic acids detection
EP3498288A1 (de) 2013-12-02 2019-06-19 Sirbal Ltd. Kräuterkombinationen zur behandlung einer hauterkrankung
CA2945263A1 (en) 2014-04-09 2015-10-15 Christopher Rudd Use of gsk-3 inhibitors or activators which modulate pd-1 or t-bet expression to modulate t cell immunity
WO2016154620A1 (en) * 2015-03-26 2016-09-29 University Of Houston System Integrated functional and molecular profiling of cells
EP3328498B1 (de) 2015-07-29 2021-05-05 Sirbal Ltd. Medizinisches kit enthaltend kräuterkombinationen zur behandlung von psoriasis
JP7021126B2 (ja) * 2016-06-28 2022-02-16 ヴェンタナ メディカル システムズ， インク． マルチ色素キノンメチド及びチラミドコンジュゲートによる発色性ｉｈｃ及びｉｓｈ染色のための新規の色
US20200123491A1 (en) * 2018-09-21 2020-04-23 Berkeley Lights, Inc. Functionalized well plate, methods of preparation and use thereof
CN109557296B (zh) * 2018-11-22 2022-05-20 珠海澳加动力生物科技有限公司 一种循环检测肿瘤细胞药物敏感性的方法
CN109975537B (zh) * 2019-04-09 2022-05-24 上海药明生物技术有限公司 一种检测tim-3抗体活性的试剂盒和方法
KR102264116B1 (ko) * 2019-06-19 2021-06-14 한국과학기술연구원 세포 소포체 내 g-단백질 연결 수용체(gpcr)의 실시간 활성 상태 분석 방법 및 컴퓨터 프로그램
CA3170531A1 (en) * 2020-02-11 2021-08-19 Absci Corporation Proximity assay
US20230265509A1 (en) * 2022-02-18 2023-08-24 David R. Kaplan Novel targets for the treatment and diagnosis of patients with atherosclerosis and enhanced risk of end organ damage

Family Cites Families (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4568649A (en) 1983-02-22 1986-02-04 Immunex Corporation Immediate ligand detection assay
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
DE3875456T3 (de) * 1987-11-09 1998-06-10 Becton Dickinson Co Verfahren zur Analyse hämatopoietischer Zellen in einer Probe.
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US4979824A (en) * 1989-05-26 1990-12-25 Board Of Trustees Of The Leland Stanford Junior University High sensitivity fluorescent single particle and single molecule detection apparatus and method
US5216414A (en) 1989-11-20 1993-06-01 Sharp Kabushiki Kaisha Color liquid crystal display device
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5199576A (en) 1991-04-05 1993-04-06 University Of Rochester System for flexibly sorting particles
US5234816A (en) 1991-07-12 1993-08-10 Becton, Dickinson And Company Method for the classification and monitoring of leukemias
US5644048A (en) 1992-01-10 1997-07-01 Isis Pharmaceuticals, Inc. Process for preparing phosphorothioate oligonucleotides
WO1993021230A1 (en) * 1992-04-10 1993-10-28 Dana-Farber Cancer Institute, Inc. Activation-state-specific phosphoprotein immunodetection
US5637684A (en) 1994-02-23 1997-06-10 Isis Pharmaceuticals, Inc. Phosphoramidate and phosphorothioamidate oligomeric compounds
US5968738A (en) 1995-12-06 1999-10-19 The Board Of Trustees Of The Leland Stanford Junior University Two-reporter FACS analysis of mammalian cells using green fluorescent proteins
US5912137A (en) 1996-07-16 1999-06-15 The Regents Of The University Of California Assays for protein kinases using fluorescent
US6280967B1 (en) * 1996-08-02 2001-08-28 Axiom Biotechnologies, Inc. Cell flow apparatus and method for real-time of cellular responses
US5804436A (en) * 1996-08-02 1998-09-08 Axiom Biotechnologies, Inc. Apparatus and method for real-time measurement of cellular response
US6558916B2 (en) * 1996-08-02 2003-05-06 Axiom Biotechnologies, Inc. Cell flow apparatus and method for real-time measurements of patient cellular responses
US6821740B2 (en) * 1998-02-25 2004-11-23 Becton, Dickinson And Company Flow cytometric methods for the concurrent detection of discrete functional conformations of PRB in single cells
WO1999044067A1 (en) * 1998-02-25 1999-09-02 New York Medical College FLOW CYTOMETRIC DETECTION OF CONFORMATIONS OF pRB IN SINGLE CELLS
US7236888B2 (en) * 1998-03-06 2007-06-26 The Regents Of The University Of California Method to measure the activation state of signaling pathways in cells
ATE248226T1 (de) 1998-04-17 2003-09-15 Rigel Pharmaceuticals Inc Multiparameter facs test zum ermitteln von änderungen in den zellularen parametern
CA2331897C (en) 1998-05-14 2008-11-18 Luminex Corporation Multi-analyte diagnostic system and computer implemented process for same
FR2782730B1 (fr) 1998-08-25 2002-05-17 Biocom Sa Procede de separation cellulaire pour l'isolation de cellules pathogeniques, notamment cancereuses rares, equipement et reactif pour la mise en oeuvre du procede et application du procede
US7300753B2 (en) 1998-09-04 2007-11-27 John Rush Immunoaffinity isolation of modified peptides from complex mixtures
US7351546B2 (en) * 1998-09-22 2008-04-01 Becton, Dickinson And Company Flow cytometric, whole blood dendritic cell immune function assay
US6495333B1 (en) * 1998-09-22 2002-12-17 Becton Dickinson And Company Flow cytometric, whole blood dendritic cell immune function assay
US6406297B1 (en) 1999-02-18 2002-06-18 The Regents Of The University Of California Salicylamide-lanthanide complexes for use as luminescent markers
US6972198B2 (en) * 1999-02-26 2005-12-06 Cyclacel, Ltd. Methods and compositions using protein binding partners
ATE429259T1 (de) * 1999-04-30 2009-05-15 Childrens Hosp Medical Center Hämofiltrationssystem
US7001725B2 (en) * 1999-04-30 2006-02-21 Aclara Biosciences, Inc. Kits employing generalized target-binding e-tag probes
US6673554B1 (en) 1999-06-14 2004-01-06 Trellie Bioinformatics, Inc. Protein localization assays for toxicity and antidotes thereto
US6406869B1 (en) 1999-10-22 2002-06-18 Pharmacopeia, Inc. Fluorescent capture assay for kinase activity employing anti-phosphotyrosine antibodies as capture and detection agents
JP2004509835A (ja) 2000-03-06 2004-04-02 ユニヴァーシティ　オブ　ケンタッキー　リサーチ　ファンデーション 血液癌前駆細胞を障害する方法およびその関連化合物
JP4798921B2 (ja) * 2000-03-06 2011-10-19 バイオシーク インコーポレーティッド 機能相同性スクリーニング
US6763307B2 (en) * 2000-03-06 2004-07-13 Bioseek, Inc. Patient classification
AU2001224349A1 (en) * 2000-04-10 2001-10-23 The Scripps Research Institute Proteomic analysis
US7045286B2 (en) 2000-07-25 2006-05-16 The Trustees Of The University Of Pennsylvania Methods of detecting molecules expressing selected epitopes via fluorescent dyes
CA2423039A1 (en) * 2000-09-20 2002-03-28 Kinetek Pharmaceuticals, Inc. Cancer associated protein kinases and their uses
EP1366146A4 (de) * 2001-02-28 2005-01-19 Merck & Co Inc "isolierte, für eine neue menschliche signalübertragungskinase mapkap-2 kodierende nukleinsäuremoleküle, kodierte proteine, damit transformierte zellen und verwendungen davon"
WO2002087431A1 (en) 2001-05-01 2002-11-07 Structural Bioinformatics, Inc. Diagnosing inapparent diseases from common clinical tests using bayesian analysis
US20020197658A1 (en) * 2001-05-10 2002-12-26 Allen Delaney Cancer associated protein kinase and its use
US7695926B2 (en) 2001-07-10 2010-04-13 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for detecting receptor-ligand interactions in single cells
US7393656B2 (en) 2001-07-10 2008-07-01 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for risk stratification
WO2003067210A2 (en) 2001-07-10 2003-08-14 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for detecting the activation state of the multiple proteins in single cells
US7381535B2 (en) 2002-07-10 2008-06-03 The Board Of Trustees Of The Leland Stanford Junior Methods and compositions for detecting receptor-ligand interactions in single cells
ES2376422T3 (es) * 2001-08-21 2012-03-13 Ventana Medical Systems, Inc. Método y ensayo de cuantificación para determinar el estado c-kit/scf/pakt.
US20030148321A1 (en) 2001-08-24 2003-08-07 Iris Pecker Methods and kits for diagnosing and monitoring hematopoietic cancers
AU2002336504A1 (en) * 2001-09-12 2003-03-24 The State Of Oregon, Acting By And Through The State Board Of Higher Education On Behalf Of Oregon S Method and system for classifying a scenario
US7894992B2 (en) 2001-11-07 2011-02-22 Board Of Trustees Of The University Of Arkansas Diagnosis and classification of multiple myeloma
JP2005523688A (ja) * 2002-01-18 2005-08-11 ブリストル−マイヤーズ　スクイブ　カンパニー タンパク質チロシンキナーゼおよび／またはタンパク質チロシンキナーゼ経路と相互作用する化合物の活性を予測するためのポリヌクレオチドおよびポリペプチドの同定
US7183385B2 (en) * 2002-02-20 2007-02-27 Cell Signaling Technology, Inc. Phospho-specific antibodies to Flt3 and uses thereof
CA2480635A1 (en) 2002-03-28 2003-10-09 Allen D. Delaney Cancer associated protein kinases and their uses
US20050281743A1 (en) * 2002-03-28 2005-12-22 Delaney Allen D Cancer associated protein phosphatases and their uses
US20040248151A1 (en) * 2002-04-05 2004-12-09 Ventana Medical Systems, Inc. Method for predicting the response to HER2-directed therapy
US20030190689A1 (en) * 2002-04-05 2003-10-09 Cell Signaling Technology,Inc. Molecular profiling of disease and therapeutic response using phospho-specific antibodies
US20030190688A1 (en) * 2002-04-05 2003-10-09 Cell Signaling Technology, Inc. Methods for detecting BCR-ABL signaling activity in tissues using phospho-specific antibodies
US7329502B2 (en) 2002-04-25 2008-02-12 The United States Of America As Represented By The Department Of Health And Human Services ZAP-70 expression as a marker for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
CA2483868A1 (en) 2002-05-03 2004-05-21 Molecular Probes, Inc. Compositions and methods for detection and isolation of phosphorylated molecules
US7460960B2 (en) * 2002-05-10 2008-12-02 Epitome Biosystems, Inc. Proteome epitope tags and methods of use thereof in protein modification analysis
JP2005532070A (ja) * 2002-07-03 2005-10-27 ザ トラスティース オブ コロンビア ユニバーシティ イン ザ シティ オブ ニューヨーク Ｍｄａ−７媒介型アポトーシスの調節因子の同定方法
US20040126784A1 (en) * 2002-07-12 2004-07-01 Rigel Pharmaceuticals, Incorporated Modulators of cellular proliferation
US7537891B2 (en) * 2002-08-27 2009-05-26 Bristol-Myers Squibb Company Identification of polynucleotides for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells
US20040137539A1 (en) * 2003-01-10 2004-07-15 Bradford Sherry A. Cancer comprehensive method for identifying cancer protein patterns and determination of cancer treatment strategies
US20040229284A1 (en) * 2003-02-19 2004-11-18 The Regents Of The University Of California Multiplex analysis of proteins
US7507548B2 (en) * 2003-03-04 2009-03-24 University Of Salamanca Multidimensional detection of aberrant phenotypes in neoplastic cells to be used to monitor minimal disease levels using flow cytometry measurements
US20050009112A1 (en) * 2003-03-07 2005-01-13 Fred Hutchinson Cancer Research Center, Office Of Technology Transfer Methods for identifying Rheb effectors as lead compounds for drug development for diabetes and diseases associated with abnormal cell growth
US6906320B2 (en) 2003-04-02 2005-06-14 Merck & Co., Inc. Mass spectrometry data analysis techniques
WO2005001115A2 (en) * 2003-05-30 2005-01-06 Odyssey Thera, Inc. Monitoring gene silencing and annotating gene function in living cells
US7402399B2 (en) * 2003-10-14 2008-07-22 Monogram Biosciences, Inc. Receptor tyrosine kinase signaling pathway analysis for diagnosis and therapy
US7326577B2 (en) * 2003-10-20 2008-02-05 Esoterix, Inc. Cell fixation and use in phospho-proteome screening
ES2359449T3 (es) * 2004-08-12 2011-05-23 Centocor Ortho Biotech Inc. Métodos para identificar condiciones que afectan a un estado celular.
US20060040338A1 (en) * 2004-08-18 2006-02-23 Odyssey Thera, Inc. Pharmacological profiling of drugs with cell-based assays
US7803523B2 (en) 2004-08-27 2010-09-28 University Health Network Whole blood preparation for cytometric analysis of cell signaling pathways
US20060216760A1 (en) 2004-12-22 2006-09-28 California Institute Of Technology Methods for proteomic profiling using non-natural amino acids
WO2006079092A2 (en) 2005-01-24 2006-07-27 The Board Of Trustees Of The Leland Stanford Junior University Method for modeling cell signaling systems by means of bayesian networks
US7939331B2 (en) 2005-03-07 2011-05-10 Life Technologies Corporation Isotopically-labeled proteome standards
DK1889065T3 (da) 2005-05-18 2013-09-02 Xoma Technology Ltd Metoder til diagnostisering og behandling af sygdomme med en autoimmun- og/eller inflammationskomponent
JP2007046697A (ja) 2005-08-10 2007-02-22 Fujikin Inc 継手付き流体制御器
US9168286B2 (en) 2005-10-13 2015-10-27 Human Genome Sciences, Inc. Methods and compositions for use in treatment of patients with autoantibody positive disease
US20070105165A1 (en) 2005-11-04 2007-05-10 Charles Goolsby Composite profiles of cell antigens and target signal transduction proteins for analysis and clinical management of hematologic cancers
US8214157B2 (en) 2006-03-31 2012-07-03 Nodality, Inc. Method and apparatus for representing multidimensional data
US20090098594A1 (en) 2007-08-21 2009-04-16 Nodality, Inc. Methods for diagnosis prognosis and methods of treatment
US7892770B2 (en) 2007-08-24 2011-02-22 Van Andel Research Institute Monoclonal antibody which binds cMet (HGFR) in formalin-fixed and paraffin-embedded tissues and related methods
US20090269800A1 (en) 2008-04-29 2009-10-29 Todd Covey Device and method for processing cell samples
US20090269773A1 (en) 2008-04-29 2009-10-29 Nodality, Inc. A Delaware Corporation Methods of determining the health status of an individual
US20090291458A1 (en) 2008-05-22 2009-11-26 Nodality, Inc. Method for Determining the Status of an Individual
GB2474613A (en) 2008-07-10 2011-04-20 Nodality Inc Methods and apparatus related to management of experiments
US20100014741A1 (en) 2008-07-10 2010-01-21 Banville Steven C Methods and apparatus related to gate boundaries within a data space
US8399206B2 (en) 2008-07-10 2013-03-19 Nodality, Inc. Methods for diagnosis, prognosis and methods of treatment
EP2304436A1 (de) 2008-07-10 2011-04-06 Nodality, Inc. Diagnose-, prognose- und behandlungsverfahren
US20100030719A1 (en) 2008-07-10 2010-02-04 Covey Todd M Methods and apparatus related to bioinformatics data analysis
EP2318836B1 (de) 2008-09-04 2013-07-31 Beckman Coulter, Inc. Pan-kinase-aktivierung und evaluierung von signalpfaden
WO2010045651A1 (en) 2008-10-17 2010-04-22 Nodality, Inc. Methods for analyzing drug response
US9034257B2 (en) 2008-10-27 2015-05-19 Nodality, Inc. High throughput flow cytometry system and method
US8309306B2 (en) 2008-11-12 2012-11-13 Nodality, Inc. Detection composition
US20100209929A1 (en) 2009-01-14 2010-08-19 Nodality, Inc., A Delaware Corporation Multiple mechanisms for modulation of jak/stat activity
US20100204973A1 (en) 2009-01-15 2010-08-12 Nodality, Inc., A Delaware Corporation Methods For Diagnosis, Prognosis And Treatment
US20100233733A1 (en) 2009-02-10 2010-09-16 Nodality, Inc., A Delaware Corporation Multiple mechanisms for modulation of the pi3 kinase pathway
US20100215644A1 (en) 2009-02-25 2010-08-26 Nodality, Inc. A Delaware Corporation Analysis of nodes in cellular pathways
US8242248B2 (en) 2009-03-23 2012-08-14 Nodality, Inc. Kits for multiparametric phospho analysis
US8187885B2 (en) 2009-05-07 2012-05-29 Nodality, Inc. Microbead kit and method for quantitative calibration and performance monitoring of a fluorescence instrument
US20100297676A1 (en) 2009-05-20 2010-11-25 Nodality, Inc. Methods for diagnosis, prognosis and methods of treatment
EP2476053A4 (de) 2009-09-08 2014-03-12 Nodality Inc Analyse von zellnetzwerken
WO2011106558A1 (en) 2010-02-24 2011-09-01 The Board Of Trustees Of The Leland Stanford Junior University Methods for autoimmune disease diagnosis, prognosis, and treatment
US20110262468A1 (en) 2010-04-23 2011-10-27 Nodality, Inc. Method for Monitoring Vaccine Response Using Single Cell Network Profiling
US20120157340A1 (en) 2010-06-09 2012-06-21 Alessandra Cesano Pathways characterization of cells

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US20060073474A1 (en) 2006-04-06
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US8962263B2 (en) 2015-02-24
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US7563584B2 (en) 2009-07-21
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