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WO2000013004B1 - Combinatorial polymer synthesis of sensors for polymer-based sensor arrays - Google Patents

Combinatorial polymer synthesis of sensors for polymer-based sensor arrays

Info

Publication number
WO2000013004B1
WO2000013004B1 PCT/US1999/019624 US9919624W WO0013004B1 WO 2000013004 B1 WO2000013004 B1 WO 2000013004B1 US 9919624 W US9919624 W US 9919624W WO 0013004 B1 WO0013004 B1 WO 0013004B1
Authority
WO
WIPO (PCT)
Prior art keywords
substrate
sensors
copolymer
sensor
detecting
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.)
Ceased
Application number
PCT/US1999/019624
Other languages
French (fr)
Other versions
WO2000013004A3 (en
WO2000013004A9 (en
WO2000013004A2 (en
Inventor
David R Walt
Todd A Dickinson
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.)
Tufts University
Original Assignee
Tufts University
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
Application filed by Tufts University filed Critical Tufts University
Priority to AU61312/99A priority Critical patent/AU6131299A/en
Publication of WO2000013004A2 publication Critical patent/WO2000013004A2/en
Publication of WO2000013004A3 publication Critical patent/WO2000013004A3/en
Publication of WO2000013004B1 publication Critical patent/WO2000013004B1/en
Publication of WO2000013004A9 publication Critical patent/WO2000013004A9/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
    • 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
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular 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
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/005—Beads
    • 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
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00513—Essentially linear 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
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B01J2219/00572—Chemical means
    • 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
    • B01J2219/0059—Sequential 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
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    • 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
    • B01J2219/0061—The surface being organic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • 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
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    • 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
    • B01J2219/00632—Introduction of reactive groups to the surface
    • B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • 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
    • B01J2219/00646—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports
    • B01J2219/00648—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports by the use of solid beads
    • 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
    • B01J2219/00704—Processes involving means for analysing and characterising the products integrated with the reactor apparatus
    • 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
    • B01J2219/00707—Processes involving means for analysing and characterising the products separated from the reactor apparatus
    • 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
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/14—Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/08—Optical fibres; light guides
    • G01N2201/0833—Fibre array at detector, resolving

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Plasma & Fusion (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)

Abstract

A combinatorial synthesis method for fabricating unique families of discrete copolymer sensors and copolymer gradient sensors is provided. The method employs combinatorial copolymer synthesis of discrete monomer or oligomer combinations as well as spatially-varying combinations for generating large numbers of analyte-discriminating sensors from a limited selection of initial monomer and oligomer compositions. The method can be applied to either analyte-specific sensors or sensor arrays or semi-selective sensors and cross-reactive sensor arrays which employ virtually any known physicochemical transduction mechanism for detecting analytes. Since the analyte response characteristics of such copolymer sensors are not limited to a linear proportional ratio of the monomer or oligomer combinations employed, the resulting copolymer sensors provide for increased diversity in sensor and sensor array response characteristics for discriminating between a variety of materials and for detecting and identifying analytes in fluid samples.

Claims

-42-
AMENDED CLAIMS
[received by the International Bureau on 5 May 2000 (05 05 00), original claims 1-16 replaced by new claims 1-16 (2 pages)]
1 A combinatorial polymer sensor comprising a) a substrate, and b) a continuous gradient of copolymers distributed on said substrate, said gradient comprising a continuously varying mixture of at least a first and a second polymeπzable material
2 A sensor array according to claim 1 wherein said substrate is a fiber optic array
3 A sensor array according to claim 1 or 2 wherein said sensors further comprise at least one dye
4 A sensor array according to claim 1 , 2 or 3 further comprising a detector for detecting sensor responses
5 A sensor array according to claim 4 wherein said detector is an optical detector
6 A method of detecting the presence of a target analyte in a sample comprising a) adding said sample to a sensor array comprising i) a substrate, and ιι) a continuous gradient of copolymers distributed on said substrate, said gradient comprising a continuously varying mixture of at least a first and a second polymeπzable material, b) detecting an alteration in a property selected from a group consisting of mass, temperature, heat, light, voltage, current, polarity, intensity, refractive index, polarization, phase, wavelength, frequency, periodicity, and dimension
7 A method according to claim 6 wherein said substrate is a fiber optic array
8 A method according to claim 6 or 7, wherein said sensors further comprise at least one dye
9 A method according to claim 6, 7 or 8, further comprising a detector for detecting sensor responses
10 A method according to claim 9 wherein said detector is an optical detector
11 A method of making a sensor array comprising a) polymerizing in a plurality of predetermined ratios i) a first solution comprising a first polymeπzable material, and ii) a second solution comprising a second polymerizable material; said ratios being unique for at least two of said solutions, such that each polymerization reaction results in a different copolymer sensor; and b) distributing said copolymer sensors on a substrate, said substrate comprising a surface comprising discrete sites.
12. A method according to claim 11 wherein said copolymer sensors are polymerized onto microspheres that are distributed on said substrate.
13. A method according to claim 11 wherein said copolymer sensors are polymerized into microspheres that are distributed on said substrate.
14. A method of making a combinatorial sensor comprising: a) providing: i) a substrate; ii) a continuously varying mixture comprising at least a first and a second polymerizable material; and b) polymerizing on said substrate at a predetermined rate said continuously varying mixture.
15. A method according to claim 11 or 14, further comprising combining at least one dye to said continuously varying mixture.
16. A method according to claim 11 or 14, wherein said substrate is a fiber optic array.
PCT/US1999/019624 1998-08-26 1999-08-26 Combinatorial polymer synthesis of sensors for polymer-based sensor arrays Ceased WO2000013004A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU61312/99A AU6131299A (en) 1998-08-26 1999-08-26 Combinatorial polymer synthesis of sensors for polymer-based sensor arrays

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14035298A 1998-08-26 1998-08-26
US09/140,352 1998-08-26

Publications (4)

Publication Number Publication Date
WO2000013004A2 WO2000013004A2 (en) 2000-03-09
WO2000013004A3 WO2000013004A3 (en) 2000-06-08
WO2000013004B1 true WO2000013004B1 (en) 2000-08-17
WO2000013004A9 WO2000013004A9 (en) 2000-10-05

Family

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PCT/US1999/019624 Ceased WO2000013004A2 (en) 1998-08-26 1999-08-26 Combinatorial polymer synthesis of sensors for polymer-based sensor arrays

Country Status (2)

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AU (1) AU6131299A (en)
WO (1) WO2000013004A2 (en)

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US6958245B2 (en) 1996-04-25 2005-10-25 Bioarray Solutions Ltd. Array cytometry
US7033754B2 (en) 1998-06-24 2006-04-25 Illumina, Inc. Decoding of array sensors with microspheres
US7211390B2 (en) 1999-09-16 2007-05-01 454 Life Sciences Corporation Method of sequencing a nucleic acid
US7244559B2 (en) 1999-09-16 2007-07-17 454 Life Sciences Corporation Method of sequencing a nucleic acid
US7361488B2 (en) 2000-02-07 2008-04-22 Illumina, Inc. Nucleic acid detection methods using universal priming
US7499806B2 (en) 2002-02-14 2009-03-03 Illumina, Inc. Image processing in microsphere arrays
US7510841B2 (en) 1998-12-28 2009-03-31 Illumina, Inc. Methods of making and using composite arrays for the detection of a plurality of target analytes
US7582420B2 (en) 2001-07-12 2009-09-01 Illumina, Inc. Multiplex nucleic acid reactions
US7595883B1 (en) 2002-09-16 2009-09-29 The Board Of Trustees Of The Leland Stanford Junior University Biological analysis arrangement and approach therefor
US7611869B2 (en) 2000-02-07 2009-11-03 Illumina, Inc. Multiplexed methylation detection methods
USRE43097E1 (en) 1994-10-13 2012-01-10 Illumina, Inc. Massively parallel signature sequencing by ligation of encoded adaptors
US8691594B2 (en) 1996-04-25 2014-04-08 Bioarray Solutions, Ltd. Method of making a microbead array with attached biomolecules
US8691754B2 (en) 2003-09-22 2014-04-08 Bioarray Solutions, Ltd. Microparticles with enhanced covalent binding capacity and their uses
US8691591B2 (en) 1997-10-06 2014-04-08 Trustees Of Tufts College Self-encoding sensor with microspheres
US9147037B2 (en) 2004-08-02 2015-09-29 Bioarray Solutions, Ltd. Automated analysis of multiplexed probe-target interaction patterns: pattern matching and allele identification
US9251583B2 (en) 2002-11-15 2016-02-02 Bioarray Solutions, Ltd. Analysis, secure access to, and transmission of array images
US9273354B2 (en) 1997-05-23 2016-03-01 Illumina, Inc. System and apparatus for sequential processing of analytes
US9279148B2 (en) 1999-04-20 2016-03-08 Illumina, Inc. Detection of nucleic acid reactions on bead arrays
US9416411B2 (en) 1999-08-18 2016-08-16 Illumina, Inc. Compositions and methods for preparing oligonucleotide solutions
US9436088B2 (en) 2001-06-21 2016-09-06 Bioarray Solutions, Ltd. Un-supported polymeric film with embedded microbeads

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US7622294B2 (en) 1997-03-14 2009-11-24 Trustees Of Tufts College Methods for detecting target analytes and enzymatic reactions
US6023540A (en) 1997-03-14 2000-02-08 Trustees Of Tufts College Fiber optic sensor with encoded microspheres
US6327410B1 (en) 1997-03-14 2001-12-04 The Trustees Of Tufts College Target analyte sensors utilizing Microspheres
US20030027126A1 (en) 1997-03-14 2003-02-06 Walt David R. Methods for detecting target analytes and enzymatic reactions
US7115884B1 (en) 1997-10-06 2006-10-03 Trustees Of Tufts College Self-encoding fiber optic sensor
US6429027B1 (en) 1998-12-28 2002-08-06 Illumina, Inc. Composite arrays utilizing microspheres
AU772719B2 (en) 1999-01-08 2004-05-06 Applera Corporation Fiber array for contacting chemical species and methods for using and making same
US7595189B2 (en) 1999-01-08 2009-09-29 Applied Biosystems, Llc Integrated optics fiber array
US6355431B1 (en) 1999-04-20 2002-03-12 Illumina, Inc. Detection of nucleic acid amplification reactions using bead arrays
US6544732B1 (en) 1999-05-20 2003-04-08 Illumina, Inc. Encoding and decoding of array sensors utilizing nanocrystals
EP1190100B1 (en) 1999-05-20 2012-07-25 Illumina, Inc. Combinatorial decoding of random nucleic acid arrays
US8080380B2 (en) 1999-05-21 2011-12-20 Illumina, Inc. Use of microfluidic systems in the detection of target analytes using microsphere arrays
US8481268B2 (en) 1999-05-21 2013-07-09 Illumina, Inc. Use of microfluidic systems in the detection of target analytes using microsphere arrays
CA2399733C (en) 2000-02-07 2011-09-20 Illumina, Inc. Nucleic acid detection methods using universal priming
US6913884B2 (en) 2001-08-16 2005-07-05 Illumina, Inc. Compositions and methods for repetitive use of genomic DNA
US6770441B2 (en) 2000-02-10 2004-08-03 Illumina, Inc. Array compositions and methods of making same
DE60136335D1 (en) 2000-02-16 2008-12-11 Illumina Inc PARALLEL GENOTYPING OF SEVERAL PATIENT SAMPLES
US9709559B2 (en) 2000-06-21 2017-07-18 Bioarray Solutions, Ltd. Multianalyte molecular analysis using application-specific random particle arrays
US6836362B2 (en) 2001-05-14 2004-12-28 General Electric Company Method for the rapid determination of the optical quality of combinatorial libraries
IL161391A0 (en) 2001-10-15 2004-09-27 Bioarray Solutions Ltd Multiplexed analysis of polymorphic loci by concurrent interrogation and enzyme-mediated detection
US7335153B2 (en) 2001-12-28 2008-02-26 Bio Array Solutions Ltd. Arrays of microparticles and methods of preparation thereof
JP2007521017A (en) 2003-10-28 2007-08-02 バイオアレイ ソリューションズ リミテッド Optimization of gene expression analysis using immobilized capture probes
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Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE43097E1 (en) 1994-10-13 2012-01-10 Illumina, Inc. Massively parallel signature sequencing by ligation of encoded adaptors
US6958245B2 (en) 1996-04-25 2005-10-25 Bioarray Solutions Ltd. Array cytometry
US9400259B2 (en) 1996-04-25 2016-07-26 Bioarray Solutions, Ltd. Method of making a microbead array with attached biomolecules
US8691594B2 (en) 1996-04-25 2014-04-08 Bioarray Solutions, Ltd. Method of making a microbead array with attached biomolecules
US9273354B2 (en) 1997-05-23 2016-03-01 Illumina, Inc. System and apparatus for sequential processing of analytes
US9157113B2 (en) 1997-10-06 2015-10-13 Trustees Of Tufts College, Tufts University Self-encoding sensor with microspheres
US8691591B2 (en) 1997-10-06 2014-04-08 Trustees Of Tufts College Self-encoding sensor with microspheres
US7033754B2 (en) 1998-06-24 2006-04-25 Illumina, Inc. Decoding of array sensors with microspheres
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