CA2251755A1 - Photolabile polymer array synthesis methods - Google Patents

Photolabile polymer array synthesis methods

Info

Publication number
CA2251755A1
CA2251755A1 CA002251755A CA2251755A CA2251755A1 CA 2251755 A1 CA2251755 A1 CA 2251755A1 CA 002251755 A CA002251755 A CA 002251755A CA 2251755 A CA2251755 A CA 2251755A CA 2251755 A1 CA2251755 A1 CA 2251755A1
Authority
CA
Canada
Prior art keywords
substrate
group
selected regions
functional groups
coupling
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.)
Granted
Application number
CA002251755A
Other languages
French (fr)
Other versions
CA2251755C (en
Inventor
Martin Goldberg
Martin Diggelman
Earl Hubbell
Glenn Mcgall
Nam Quoc Ngo
Macdonald Morris
Mel Yamamoto
Jennifer Tan
Richard P. Rava
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.)
Affymetrix Inc
Original Assignee
Affymetrix, Inc.
Martin Goldberg
Martin Diggelman
Earl Hubbell
Glenn Mcgall
Nam Quoc Ngo
Macdonald Morris
Mel Yamamoto
Jennifer Tan
Richard P. Rava
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 Affymetrix, Inc., Martin Goldberg, Martin Diggelman, Earl Hubbell, Glenn Mcgall, Nam Quoc Ngo, Macdonald Morris, Mel Yamamoto, Jennifer Tan, Richard P. Rava filed Critical Affymetrix, Inc.
Publication of CA2251755A1 publication Critical patent/CA2251755A1/en
Application granted granted Critical
Publication of CA2251755C publication Critical patent/CA2251755C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/047—Simultaneous synthesis of different peptide species; Peptide libraries
    • 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
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • 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
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00427—Means for dispensing and evacuation of reagents using masks
    • B01J2219/00432—Photolithographic masks
    • 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
    • B01J2219/00527—Sheets
    • 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
    • B01J2219/00527—Sheets
    • B01J2219/00529—DNA chips
    • 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
    • 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
    • B01J2219/00608—DNA chips
    • 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
    • B01J2219/0061—The surface being organic
    • 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
    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
    • 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
    • B01J2219/00605—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
    • 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
    • B01J2219/00686—Automatic
    • B01J2219/00689—Automatic using computers
    • 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
    • B01J2219/00709—Type of synthesis
    • B01J2219/00711—Light-directed synthesis
    • 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
    • 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
    • B01J2219/00725—Peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support
    • 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
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • 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
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
    • 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
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/807—Apparatus included in process claim, e.g. physical support structures
    • Y10S436/809—Multifield plates or multicontainer arrays

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Nanotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Composite Materials (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Materials Engineering (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)

Abstract

The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Claims (49)

1. A method of forming an array of polymers on a surface of a substrate, comprising:
providing a substrate having a first surface coated with functional groups protected with a photolabile protecting group, and a second surface having a layer disposed thereon, said layer including one or more of an index matching compound, a light absorbing compound and an antireflective compound; and sequentially activating and coupling monomers in different selected regions of said substrate to form a plurality of different polymer sequences in different known locations on said surface of said substrate, wherein said activating step comprises directing an activation radiation at said first surface of said substrate.
2. The method according to claim 1, wherein said layer disposed upon said second surface of said substrate comprises an index matching compound.
3. The method according to claim 1, wherein said layer disposed upon said second surface of said substrate is an antireflective compound.
4. The method according to claim 1, wherein said layer disposed upon said second surface of said substrate comprises an index matching compound and a light absorbing compound.
5. The method according to claim 1, wherein said layer disposed upon said second surface of said substrate comprises polyimide.
6. The method according to claim 1, wherein said plurality of different polymer sequences comprises a plurality of different oligonucleotide sequences.
7. A method of forming a plurality of individual polymer arrays, comprising:
providing a plurality of substrate wafers, each of said substrate wafers having a first surface, said first surface having functional groups disposed thereon, said functional groups being protected with a removable protecting group;
exposing a plurality of first selected regions on said first surface of each of said substrate wafers to an activator at an activation station to remove said removable protecting groups from said functional groups in said first selected regions;
first moving said substrate wafers batch-wise to a coupling station;
contacting said plurality of wafers with a monomer containing solution at said coupling station, to couple first selected monomers to said functional groups in said selected regions on said surface of said plurality of substrate wafers;
first returning said substrate wafers batch-wise to said activation station;
exposing a plurality of second selected regions on said first surface of each of said substrate wafers to an activator at said activation station to remove said removable protecting groups from said functional groups in said second selected regions;
second moving said substrate wafers batch-wise to said coupling station;
contacting said plurality of wafers with a monomer containing solution in said coupling station, to couple second selected monomers to said functional groups in said selected regions on said surface of said plurality of substrate wafers;
repeating said exposing and contacting steps to form a plurality of individual polymer arrays on said first surface of each of said substrate wafers.
8. The method according to claim 7, wherein said contacting steps comprise simultaneously contacting said plurality of substrate wafers with said monomer containing solutions.
9. The method according to claim 7, wherein said removable protecting group is a photolabile protecting group and said activator is light.
10. The method according to claim 7, wherein said exposing step comprises simultaneously contacting at least a first of said plurality of substrate wafers with a first monomer containing solution and contacting a second of said plurality of substrate wafers with a second monomer containing solution.
11. The method according to claim 7, wherein said activator comprises an activation radiation and said exposing step comprises directing said activation radiation at said first surface of said plurality of substrate wafers, and wherein a second surface of said plurality of substrate wafers includes a layer of one or more of an index matching compound, a light absorbing compound and an antireflective compound disposed thereon.
12. The method according to claim 11, wherein said layer disposed upon said second surface of said substrate comprises an index matching compound.
13. The method according to claim 11, wherein said layer disposed upon said second surface of said substrate is an antireflective compound.
14. The method according to claim 11, wherein said layer disposed upon said second surface of said substrate comprises an index matching compound and a light absorbing compound.
15. The method according to claim 11, wherein said layer disposed upon said second surface of said substrate comprises polyimide.
16. The method according to claim 7, wherein said plurality of different polymer sequences comprises a plurality of different oligonucleotide sequences.
17. A method of forming an array of polymers on a surface of a substrate, comprising:
derivatizing said surface of said substrate by contacting said surface of said substrate with a solution of aminoalkyltrialkoxysilane to provide amine functional groups on said first surface of said substrate;
protecting said functional groups with a protecting group;
activating first selected regions on said first surface of said substrate by removing said protecting groups from said functional groups in said first selected regions;
coupling a first monomer to said functional groups in said first selected regions;
activating second selected regions on said first surface of said substrate by removing said protecting groups from said functional groups in said second selected regions;
coupling a second monomer to said functional groups in said second selected regions;
repeating said activating and coupling steps to form a plurality of different polymer sequences, each of said different polymer sequences being coupled to said surface of said substrate in a different known location.
18. The method according to claim 17, wherein said first and second monomers coupled in said coupling steps comprise an active phosphoramidite group.
19. The method according to claim 17, wherein said first and second monomers comprise nucleosides.
20. The method according to claim 17, wherein said aminoalkyltrialkoxysilane is selected from the group consisting of 3-aminopropyltriethoxysilane and 3-aminopropyltrimethoxysilane.
21. The method according to claim 17, wherein in said derivatizing step, said contacting of said surface of said substrate with a solution of aminoalkyltrialkoxysilane is carried out by controlled vapor deposition of said aminoalkyltrialkoxysilane on said surface.
22. The method according to claim 17, wherein said plurality of different polymer sequences comprises a plurality of different oligonucleotide sequences.
23. A method of forming an array of polymers on a surface of a substrate, comprising:
stripping said surface of said substrate with a stripping solution;
providing functional groups on said surface of said substrate;
protecting said functional groups with a photolabile protecting group;
exposing first selected regions on said first surface of said substrate to an activation radiation to remove said photolabile protecting groups from said functional groups in said first selected regions;
coupling a first monomer to said functional groups in said first selected regions;
exposing second selected regions on said first surface of said substrate wafers to an activation radiation to remove said photolabile protecting groups from said functional groups in said second selected regions;
coupling a second monomer to said functional groups in said second selected regions;
repeating said exposing and coupling steps to form a plurality of different polymer sequences, each of said different polymer sequences being coupled to said surface of said substrate in a different known location.
24. The method according to claim 23, wherein said stripping step comprises contacting said surface of said substrate with a stripping solution of concentrated NaOH/H2O2.
25. The method according to claim 23, wherein said stripping step further comprises:
contacting said surface of said substrate with base;
and rinsing said substrate with acid.
26. A method of coupling monomers to selected regions on a surface of a substrate, comprising:
providing functional groups on said surface of said substrate, said functional groups being protected with a photoprotecting group;
exposing said selected regions to an activation radiation to remove said photolabile protecting group in said selected regions, said exposing step comprising directing an activation radiation at said selected regions on said surface of said substrate by shining said activation radiation through a photolithographic mask, said photolithographic mask including transparent regions and opaque regions, said transparent regions being smaller than said selected regions, whereby when said activation radiation is shone through said transparent regions in said mask, said activation radiation is diffracted to expose substantially all of said selected regions; and coupling monomers to said functional groups in said selected regions.
27. The method according to claim 26, wherein said transparent regions in said mask are from about 2% to about 25% smaller in each dimension than said selected regions.
28. The method according to claim 26, wherein said transparent regions in said mask are from about 10% to about 20% smaller in each dimension than said selected regions.
29. A method of forming polymer sequences on a solid substrate, comprising:
providing functional groups on said surface of said substrate;

coupling monomers to said functional groups on said surface of said substrate, said monomers having chemical groups reversibly coupled thereto, whereby said chemical groups enhance the lipophilicity of said monomers.
30. The method according to claim 29, wherein said monomer comprises a nucleotide protected with a lipophilic protecting group.
31. The method according to claim 30, wherein said lipophilic protecting group is coupled to an exocyclic functional group in a nucleobase in said nucleotide.
32. The method according to claim 31, wherein said exocyclic functional group is protected with a DMT protecting group.
33. The method according to claim 30, wherein said lipophilic protecting group is a photolabile protecting group.
34. The method according to claim 30, wherein said monomer comprises a nucleoside Fmoc-phosphoramidite.
35. A method of deprotecting an array of polymer sequences synthesized on a solid support, comprising contacting said array with a solution containing a substituted alkylamine.
36. The method according to claim 35, wherein said substituted alkylamine is selected from the group consisting of ethanolamine and ethylenediamine.
37. The method according to claim 35, wherein said solution of substituted alkylamine is a solution of ethylenediamine in ethanol.
38. The method according to claim 35, wherein said solution containing alkylamine is a 1:1 solution of ethylenediamine in ethanol.
39. A method of forming an array of polymer sequences on a surface of a substrate by sequentially deprotecting and coupling monomers in selected regions of said surface of said substrate to produce a plurality of different polymer sequences in different known locations of said surface of said substrate, the method comprising aligning deprotection and coupling steps in adjacent selected regions to minimize a number of differential synthesis steps between said adjacent regions.
40. A method of forming an array of polymer sequences wherein each polymer sequence has a subsequence of monomers common to a sequence that is complementary to a target sequence, but wherein at least one position within said subsequence is substituted with each member of a basis set of monomers, the method comprising coupling all monomers in a same layer of a first of said polymer sequences in a same synthesis cycle as corresponding monomers in a second of said polymer sequences.
41. A method of photoprotecting a functional group coupled to a solid support, the method comprising exposing said functional group to a photoprotecting group transfer agent having the formula:

wherein R1 is a photolabile protecting group and X is a leaving group.
42. The method according to claim 41, wherein X is selected from the group consisting of:

where R2 is alkyl, substituted alkyl or aryl, R3 is hydrogen, alkyl, thioalkyl, aryl; R4 is an electron withdrawing group;
R5 is a sterically hindered alkyl or aryl group; and R6 is alkyl or aryl group said alkyl or aryl group comprising an electronegative substituent.
43. The method according to claim 42, wherein R4 is selected from the group consisting of NO2, SO2-R2, and CN.
44 . The method according to claim 42, wherein R5 is selected from the group consisting of adamantyl and t-butyl.
45. The method according to claim 42, wherein said electronegative substituent is selected from the group consisting of:

46. The method according to claim 41, wherein R1 is selected from the group consisting of NVOC, NPOC, MeNVOC, MeNPOC, PYMOC, NV, NP, MeNV and MeNP.
47. The method according to claim 41, wherein said exposing step is carried out in the presence of a nonnucleophilic organic solvent and a base catalyst.
48. The method according to claim 47, wherein said nonnucleophilic organic solvent is selected from the group consisting of DMF, NMP, DCM, THF and ACN.
49. The method according to claim 47, wherein said base catalyst is selected from the group consisting of pyridine, 2,6-lutidine, TEA and DIEA.
CA2251755A 1996-04-17 1997-04-16 Photolabile polymer array synthesis methods Expired - Lifetime CA2251755C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/634,053 1996-04-17
US08/634,053 US5959098A (en) 1996-04-17 1996-04-17 Substrate preparation process
PCT/US1997/006535 WO1997039151A1 (en) 1996-04-17 1997-04-16 Photolabile polymer array synthesis methods

Publications (2)

Publication Number Publication Date
CA2251755A1 true CA2251755A1 (en) 1997-10-23
CA2251755C CA2251755C (en) 2010-09-14

Family

ID=24542253

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2251755A Expired - Lifetime CA2251755C (en) 1996-04-17 1997-04-16 Photolabile polymer array synthesis methods

Country Status (6)

Country Link
US (6) US5959098A (en)
EP (1) EP0950112A4 (en)
JP (2) JP2000508542A (en)
AU (1) AU2804797A (en)
CA (1) CA2251755C (en)
WO (1) WO1997039151A1 (en)

Families Citing this family (325)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5959098A (en) 1996-04-17 1999-09-28 Affymetrix, Inc. Substrate preparation process
US20110028350A1 (en) * 1995-12-15 2011-02-03 Affymetrix, Inc. Photocleavable protecting groups
US6147205A (en) * 1995-12-15 2000-11-14 Affymetrix, Inc. Photocleavable protecting groups and methods for their use
US6706875B1 (en) * 1996-04-17 2004-03-16 Affyemtrix, Inc. Substrate preparation process
DE69737883T2 (en) 1996-04-25 2008-03-06 Bioarray Solutions Ltd. LIGHT-REGULATED, ELECTROKINETIC COMPOSITION OF PARTICLES TO SURFACES
PT1017848E (en) 1997-07-28 2003-02-28 Medical Biosystems Ltd ANALYSIS OF NUCLEIC ACID SEQUENCES
NO306357B1 (en) * 1997-10-16 1999-10-25 Torstein Ljungmann Color machine for preparation of tissue samples placed on slides
US6251588B1 (en) * 1998-02-10 2001-06-26 Agilent Technologies, Inc. Method for evaluating oligonucleotide probe sequences
AU772531B2 (en) * 1998-02-11 2004-04-29 University Of Houston, The Method and apparatus for chemical and biochemical reactions using photo-generated reagents
ATE246041T1 (en) * 1998-02-11 2003-08-15 Univ Houston Office Of Technol DEVICE FOR CARRYING OUT CHEMICAL AND BIOCHEMICAL REACTIONS USING PHOTOPRODUCED REAGENTS
DE69942272D1 (en) * 1998-02-23 2010-06-02 Wisconsin Alumni Res Found DERANORDNUNGEN
US6235480B1 (en) * 1998-03-13 2001-05-22 Promega Corporation Detection of nucleic acid hybrids
US6391005B1 (en) 1998-03-30 2002-05-21 Agilent Technologies, Inc. Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
JP2002512045A (en) * 1998-04-20 2002-04-23 アフィメトリックス インコーポレイテッド Methods for reducing non-specific binding to nucleic acid probe arrays
US6979728B2 (en) * 1998-05-04 2005-12-27 Baylor College Of Medicine Articles of manufacture and methods for array based analysis of biological molecules
US6048695A (en) * 1998-05-04 2000-04-11 Baylor College Of Medicine Chemically modified nucleic acids and methods for coupling nucleic acids to solid support
US6271957B1 (en) * 1998-05-29 2001-08-07 Affymetrix, Inc. Methods involving direct write optical lithography
US6295153B1 (en) * 1998-06-04 2001-09-25 Board Of Regents, The University Of Texas System Digital optical chemistry micromirror imager
AU754952B2 (en) 1998-06-24 2002-11-28 Illumina, Inc. Decoding of array sensors with microspheres
DE19940749A1 (en) 1998-08-28 2000-05-18 Febit Ferrarius Biotech Gmbh Integrated synthesis and analysis method e.g. for polymers, comprises a carrier body provided with immobilized receptors to provide respective channels before contact with sample and subsequent analysis
DE19842164B4 (en) * 1998-09-15 2004-06-03 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Quality control procedures for the construction of oligomer grids
US6703228B1 (en) 1998-09-25 2004-03-09 Massachusetts Institute Of Technology Methods and products related to genotyping and DNA analysis
US6262216B1 (en) 1998-10-13 2001-07-17 Affymetrix, Inc. Functionalized silicon compounds and methods for their synthesis and use
US6951682B1 (en) * 1998-12-01 2005-10-04 Syntrix Biochip, Inc. Porous coatings bearing ligand arrays and use thereof
GB9906929D0 (en) * 1999-03-26 1999-05-19 Univ Glasgow Assay system
AU4207600A (en) * 1999-04-08 2000-11-14 Affymetrix, Inc. Porous silica substrates for polymers synthesis and assays
US6824866B1 (en) 1999-04-08 2004-11-30 Affymetrix, Inc. Porous silica substrates for polymer synthesis and assays
US20020177135A1 (en) * 1999-07-27 2002-11-28 Doung Hau H. Devices and methods for biochip multiplexing
WO2000079006A1 (en) * 1999-06-17 2000-12-28 Fred Hutchinson Cancer Research Center Oligonucleotide arrays for high resolution hla typing
JP3471664B2 (en) * 1999-07-08 2003-12-02 Ｎｅｃ液晶テクノロジー株式会社 Cutting device for bonded substrates for liquid crystal cells
EP1212461A4 (en) * 1999-09-02 2006-10-18 Corning Inc Porous substrates for dna arrays
US6994972B2 (en) * 1999-09-02 2006-02-07 Corning Incorporated Porous substrates for DNA arrays
US6750023B2 (en) * 1999-09-02 2004-06-15 Corning Incorporated Porous inorganic substrate for high-density arrays
US7115423B1 (en) * 1999-10-22 2006-10-03 Agilent Technologies, Inc. Fluidic structures within an array package
WO2001032935A2 (en) * 1999-11-02 2001-05-10 Celine Hu Molecular microarrays and methods for production and use thereof
US6784982B1 (en) * 1999-11-04 2004-08-31 Regents Of The University Of Minnesota Direct mapping of DNA chips to detector arrays
US6867851B2 (en) * 1999-11-04 2005-03-15 Regents Of The University Of Minnesota Scanning of biological samples
US6642046B1 (en) 1999-12-09 2003-11-04 Motorola, Inc. Method and apparatus for performing biological reactions on a substrate surface
US6800439B1 (en) 2000-01-06 2004-10-05 Affymetrix, Inc. Methods for improved array preparation
US6458526B1 (en) 2000-01-28 2002-10-01 Agilent Technologies, Inc. Method and apparatus to inhibit bubble formation in a fluid
US20030013096A1 (en) * 2000-03-16 2003-01-16 Ichiro Yamashita Nucleotide detector, process for producing the same and process for morming forming fine particle membrane
US6806361B1 (en) 2000-03-17 2004-10-19 Affymetrix, Inc. Methods of enhancing functional performance of nucleic acid arrays
US6833450B1 (en) 2000-03-17 2004-12-21 Affymetrix, Inc. Phosphite ester oxidation in nucleic acid array preparation
CA2408767A1 (en) * 2000-05-12 2001-11-15 Kyowa Hakko Kogyo Co., Ltd. Method and device for prepaping polynucleotide microarray and polynucleotide microarray
US7005259B1 (en) * 2000-06-01 2006-02-28 Affymetrix, Inc. Methods for array preparation using substrate rotation
JP4744778B2 (en) 2000-06-21 2011-08-10 バイオアレイ ソルーションズ リミテッド Method for analyzing multiple analyte molecules using a specific random particle array
US9709559B2 (en) 2000-06-21 2017-07-18 Bioarray Solutions, Ltd. Multianalyte molecular analysis using application-specific random particle arrays
US20040161789A1 (en) * 2000-08-30 2004-08-19 Tanner Cameron W. Porous inorganic substrate for high-density arrays
AU2001292142A1 (en) * 2000-09-11 2002-03-22 Affymetrix, Inc. Photocleavable protecting groups
GB0022978D0 (en) 2000-09-19 2000-11-01 Oxford Glycosciences Uk Ltd Detection of peptides
US20020037359A1 (en) * 2000-09-25 2002-03-28 Mutz Mitchell W. Focused acoustic energy in the preparation of peptide arrays
US6864097B1 (en) 2000-09-27 2005-03-08 Agilent Technologies, Inc. Arrays and their reading
US20060141507A1 (en) * 2000-09-27 2006-06-29 Kronick Mel N Manufacture and use of non-standard size microarray slides
DE10051396A1 (en) 2000-10-17 2002-04-18 Febit Ferrarius Biotech Gmbh An integrated synthesis and identification of an analyte, comprises particles immobilized at a carrier to be coupled to receptors in a structured pattern to give receptor arrays for biochemical reactions
US6835534B2 (en) * 2000-10-27 2004-12-28 The Penn State Research Foundation Chemical functionalization nanolithography
US6528264B1 (en) * 2000-11-01 2003-03-04 Corning Incorporated Polymer support for DNA immobilization
US20020150887A1 (en) * 2000-11-09 2002-10-17 National Institute Of Advanced Industrial Science And Technology Methods and nucleic acid probes for molecular genetic analysis of polluted environments and environmental samples
US8641644B2 (en) 2000-11-21 2014-02-04 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US7117095B2 (en) * 2000-11-21 2006-10-03 Affymetrix, Inc. Methods for selecting nucleic acid probes
US20020075490A1 (en) * 2000-12-20 2002-06-20 Affymetrix, Inc. System and method for addressable light-directed microarray printing
WO2002052045A1 (en) * 2000-12-26 2002-07-04 Aviva Biosciences Active and biocompatible platforms prepared by polymerization of surface coating films
DE60030306T2 (en) * 2000-12-28 2007-08-30 Roche Diagnostics Gmbh Method, system and cartridge for processing a nucleic acid sample by oscillation of the cartridge
US6870011B2 (en) 2001-01-24 2005-03-22 Arizona Chemical Company Hydrocarbon-terminated polyether-polyamide block copolymers and uses thereof
US6399713B1 (en) 2001-01-24 2002-06-04 Arizona Chemical Company Hydrocarbon-terminated polyether-polyamide block copolymers and uses thereof
EP1404233B1 (en) 2001-06-12 2009-12-02 Pelikan Technologies Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
EP1404235A4 (en) 2001-06-12 2008-08-20 Pelikan Technologies Inc Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US9226699B2 (en) 2002-04-19 2016-01-05 Sanofi-Aventis Deutschland Gmbh Body fluid sampling module with a continuous compression tissue interface surface
US7025774B2 (en) 2001-06-12 2006-04-11 Pelikan Technologies, Inc. Tissue penetration device
US7981056B2 (en) 2002-04-19 2011-07-19 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US8337419B2 (en) 2002-04-19 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
JP4149911B2 (en) 2001-06-12 2008-09-17 ペリカン テクノロジーズ インコーポレイテッド Electric lancet actuator
US7262063B2 (en) 2001-06-21 2007-08-28 Bio Array Solutions, Ltd. Directed assembly of functional heterostructures
US6649348B2 (en) * 2001-06-29 2003-11-18 Agilent Technologies Inc. Methods for manufacturing arrays
EP1417337B1 (en) * 2001-07-11 2009-03-04 Baylor College of Medicine Methods and devices based upon a novel form of nucleic acid duplex on a surface
US10272409B2 (en) 2001-07-11 2019-04-30 Michael E. Hogan Methods and devices based upon a novel form of nucleic acid duplex on a surface
US7297553B2 (en) * 2002-05-28 2007-11-20 Nanosphere, Inc. Method for attachment of silylated molecules to glass surfaces
WO2003006676A2 (en) * 2001-07-13 2003-01-23 Nanosphere, Inc. Method for immobilizing molecules onto surfaces
US6916541B2 (en) * 2001-09-07 2005-07-12 Penn State Research Foundation Modified substrates for the attachment of biomolecules
US6993173B2 (en) * 2001-10-12 2006-01-31 Duke University Methods for estimating probe cell locations in high-density synthetic DNA microarrays
US7439346B2 (en) 2001-10-12 2008-10-21 Perkinelmer Las Inc. Nucleic acids arrays and methods of use therefor
AU2002334769A1 (en) * 2001-10-12 2003-04-28 Duke University Image analysis of high-density synthetic dna microarrays
CA2463725A1 (en) 2001-10-12 2003-11-06 Spectral Genomics, Inc. Compilations of nucleic acids and arrays and methods of using them
JP4377689B2 (en) 2001-10-15 2009-12-02 バイオアレイ ソリューションズ リミテッド Combined analysis of polymorphic loci with simultaneous interrogation and enzyme-mediated detection
US20030073089A1 (en) * 2001-10-16 2003-04-17 Mauze Ganapati R. Companion cartridge for disposable diagnostic sensing platforms
US20030157700A1 (en) * 2001-12-19 2003-08-21 Affymetrix, Inc. Apparatus and methods for constructing array plates
US7335153B2 (en) 2001-12-28 2008-02-26 Bio Array Solutions Ltd. Arrays of microparticles and methods of preparation thereof
US7422851B2 (en) * 2002-01-31 2008-09-09 Nimblegen Systems, Inc. Correction for illumination non-uniformity during the synthesis of arrays of oligomers
US7083975B2 (en) * 2002-02-01 2006-08-01 Roland Green Microarray synthesis instrument and method
US20030162283A1 (en) * 2002-02-22 2003-08-28 Hitachi, Ltd. Circulating type biochemical reaction apparatus
US6916621B2 (en) 2002-03-27 2005-07-12 Spectral Genomics, Inc. Methods for array-based comparitive binding assays
US6773888B2 (en) 2002-04-08 2004-08-10 Affymetrix, Inc. Photoactivatable silane compounds and methods for their synthesis and use
US7175642B2 (en) 2002-04-19 2007-02-13 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US7229458B2 (en) 2002-04-19 2007-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7547287B2 (en) 2002-04-19 2009-06-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
BRPI0309391B1 (en) 2002-04-19 2018-10-30 Dsm Food Specialties B V vector comprising nucleic acid encoding phospholipase activity polypeptide, transformed cell, protein preparation, preparation method and related methods
US7226461B2 (en) 2002-04-19 2007-06-05 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with sterility barrier release
US8372016B2 (en) 2002-04-19 2013-02-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling and analyte sensing
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7909778B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8360992B2 (en) 2002-04-19 2013-01-29 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9795334B2 (en) 2002-04-19 2017-10-24 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US7232451B2 (en) 2002-04-19 2007-06-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7226771B2 (en) 2002-04-19 2007-06-05 Diversa Corporation Phospholipases, nucleic acids encoding them and methods for making and using them
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7297122B2 (en) 2002-04-19 2007-11-20 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7491178B2 (en) 2002-04-19 2009-02-17 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7331931B2 (en) 2002-04-19 2008-02-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
US7217512B2 (en) * 2002-05-09 2007-05-15 Corning Incorporated Reagent and method for attaching target molecules to a surface
KR100451663B1 (en) * 2002-05-15 2004-10-08 한국전자통신연구원 Programmable mask and a method for fabricating biomolecule array using the same
US20070275411A1 (en) 2006-05-25 2007-11-29 Mcgall Glenn H Silane mixtures
US7332273B2 (en) * 2002-06-20 2008-02-19 Affymetrix, Inc. Antireflective coatings for high-resolution photolithographic synthesis of DNA arrays
US7220573B2 (en) * 2002-06-21 2007-05-22 Agilent Technologies, Inc. Array assay devices and methods of using the same
EP1552003A4 (en) * 2002-06-28 2007-06-13 Rosetta Inpharmatics Llc Methods to assess quality of microarrays
US7504215B2 (en) 2002-07-12 2009-03-17 Affymetrix, Inc. Nucleic acid labeling methods
US20040101444A1 (en) * 2002-07-15 2004-05-27 Xeotron Corporation Apparatus and method for fluid delivery to a hybridization station
US7452712B2 (en) 2002-07-30 2008-11-18 Applied Biosystems Inc. Sample block apparatus and method of maintaining a microcard on a sample block
GB0217963D0 (en) * 2002-08-02 2002-09-11 Cyclops Genome Sciences Ltd Purification of nucleic acids
WO2004024895A2 (en) * 2002-09-16 2004-03-25 Plexxikon, Inc. Crystal structure of pim-1 kinase
CA2500783C (en) 2002-10-01 2012-07-17 Nimblegen Systems, Inc. Microarrays having multiple oligonucleotides in single array features
US20040076961A1 (en) * 2002-10-21 2004-04-22 Lewis Mark A. Biomolecule retaining material and methods for attaching biomolecules to a surface
US7195908B2 (en) * 2002-10-31 2007-03-27 Corning Incorporated Supports treated with triamine for immobilizing biomolecules
AU2003298655A1 (en) 2002-11-15 2004-06-15 Bioarray Solutions, Ltd. Analysis, secure access to, and transmission of array images
US20040137606A1 (en) * 2002-12-11 2004-07-15 Jung Moon Youn Programmable mask for forming biomolecule or polymer array and fabrication method of biomolecule or polymer array using the same
US20040180368A1 (en) * 2002-12-23 2004-09-16 Affymetrix, Inc. Method for producing a high density nucleic acid array using activators
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US20050048573A1 (en) * 2003-02-03 2005-03-03 Plexxikon, Inc. PDE5A crystal structure and uses
US20040152085A1 (en) * 2003-02-04 2004-08-05 Veridian Systems Division Surface for collection and/or purification of nucleic acids
US7223851B2 (en) * 2003-02-06 2007-05-29 General Dynamics Advanced Information Systems, Inc. Nucleic acid-binding polymers
JP2007524374A (en) * 2003-02-28 2007-08-30 プレキシコン，インコーポレーテッド PYK2 crystal structure and use
EP2194133B1 (en) 2003-03-06 2015-12-02 BASF Enzymes LLC Amylases, nucleic acids encoding them and methods for making and using them
US20040175504A1 (en) * 2003-03-06 2004-09-09 Zyomyx, Inc. Substrate processing apparatus and method for the controlled formation of layers including self-assembled monolayers
MX295545B (en) 2003-03-07 2012-02-03 Diversa Corp Hydrolases, nucleic acids encoding them and mehods for making and using them.
JP2004279196A (en) * 2003-03-14 2004-10-07 Dainippon Printing Co Ltd Substrate for bio-micro-array and bio-micro-array
MXPA05010681A (en) 2003-04-04 2005-12-15 Diversa Corp Pectate lyases, nucleic acids encoding them and methods for making and using them.
ES2347248T3 (en) 2003-05-30 2010-10-27 Pelikan Technologies Inc. PROCEDURE AND APPLIANCE FOR FLUID INJECTION.
US7850621B2 (en) 2003-06-06 2010-12-14 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
CA3084542A1 (en) 2003-06-10 2005-01-06 The Trustees Of Boston University Gene expression analysis of airway epithelial cells for diagnosing lung cancer
WO2006001797A1 (en) 2004-06-14 2006-01-05 Pelikan Technologies, Inc. Low pain penetrating
US7960148B2 (en) 2003-07-02 2011-06-14 Verenium Corporation Glucanases, nucleic acids encoding them and methods for making and using them
US20050079548A1 (en) * 2003-07-07 2005-04-14 Plexxikon, Inc. Ligand development using PDE4B crystal structures
US20050048571A1 (en) * 2003-07-29 2005-03-03 Danielson Paul S. Porous glass substrates with reduced auto-fluorescence
WO2005021714A2 (en) 2003-08-11 2005-03-10 Diversa Corporation Laccases, nucleic acids encoding them and methods for making and using them
US20050164300A1 (en) * 2003-09-15 2005-07-28 Plexxikon, Inc. Molecular scaffolds for kinase ligand development
WO2005029705A2 (en) 2003-09-18 2005-03-31 Bioarray Solutions, Ltd. Number coding for identification of subtypes of coded types of solid phase carriers
NZ546072A (en) 2003-09-22 2009-08-28 Bioarray Solutions Ltd Surface immobilized polyelectrolyte with multiple functional groups capable of covalently bonding to biomolecules
EP1671096A4 (en) 2003-09-29 2009-09-16 Pelikan Technologies Inc Method and apparatus for an improved sample capture device
WO2005037095A1 (en) 2003-10-14 2005-04-28 Pelikan Technologies, Inc. Method and apparatus for a variable user interface
WO2005042763A2 (en) 2003-10-28 2005-05-12 Bioarray Solutions Ltd. Optimization of gene expression analysis using immobilized capture probes
EP1694859B1 (en) 2003-10-29 2015-01-07 Bioarray Solutions Ltd Multiplexed nucleic acid analysis by fragmentation of double-stranded dna
CA2544178A1 (en) * 2003-10-30 2005-05-19 Tufts-New England Medical Center Prenatal diagnosis using cell-free fetal dna in amniotic fluid
FR2861608B1 (en) * 2003-10-31 2005-12-23 Commissariat Energie Atomique WORKING DEVICE COMPRISING WORKED AREAS, LABORATORY ON CHIP AND MICROSYSTEM
EP1709198B1 (en) 2003-11-26 2013-08-14 AdvanDx, Inc. Peptide nucleic acid probes for analysis of certain staphylococcus species
JP5138938B2 (en) 2003-12-19 2013-02-06 プレキシコン インコーポレーテッド Compounds and methods for the development of RET modulators
US20070066641A1 (en) * 2003-12-19 2007-03-22 Prabha Ibrahim Compounds and methods for development of RET modulators
EP1547678B1 (en) * 2003-12-22 2016-07-13 Affymetrix, Inc. Process for high-yield synthesis of nucleic acid arrays
US8668656B2 (en) 2003-12-31 2014-03-11 Sanofi-Aventis Deutschland Gmbh Method and apparatus for improving fluidic flow and sample capture
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
US20050191682A1 (en) 2004-02-17 2005-09-01 Affymetrix, Inc. Methods for fragmenting DNA
US20050214777A1 (en) * 2004-03-29 2005-09-29 Peck Bill J Methods for in situ generation of nucleic acid arrays
US20050214778A1 (en) * 2004-03-29 2005-09-29 Peck Bill J Methods for in situ generation of nucleic acid arrays
US7384779B2 (en) * 2004-04-12 2008-06-10 Corning Incorporated Porous substrate plates and the use thereof
JP2008503446A (en) 2004-05-06 2008-02-07 プレキシコン，インコーポレーテッド PDE4B inhibitor and use thereof
JP5149622B2 (en) * 2004-05-20 2013-02-20 クエスト ダイアグノスティックス インヴェストメンツ インコーポレイテッド Single label comparative hybridization
EP1751546A2 (en) 2004-05-20 2007-02-14 Albatros Technologies GmbH & Co. KG Printable hydrogel for biosensors
WO2005120365A1 (en) 2004-06-03 2005-12-22 Pelikan Technologies, Inc. Method and apparatus for a fluid sampling device
US9775553B2 (en) 2004-06-03 2017-10-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
ES2461857T3 (en) 2004-06-16 2014-05-21 Dsm Ip Assets B.V. Compositions and methods for enzymatic discoloration of chlorophyll
CA2570817A1 (en) * 2004-06-17 2006-01-26 Plexxikon, Inc. Azaindoles modulating c-kit activity and uses therefor
US7498342B2 (en) 2004-06-17 2009-03-03 Plexxikon, Inc. Compounds modulating c-kit activity
JP4654627B2 (en) * 2004-07-26 2011-03-23 セイコーエプソン株式会社 Chemical adsorption film forming method and chemical adsorption film
FR2873697B1 (en) * 2004-07-28 2006-10-27 Commissariat Energie Atomique PHOTOLABILE PROTECTIVE GROUPING COUPLING AGENTS AND THEIR USES, IN PARTICULAR FOR THE FUNCTIONALIZATION OF SOLID SUPPORTS
US7848889B2 (en) 2004-08-02 2010-12-07 Bioarray Solutions, Ltd. Automated analysis of multiplexed probe-target interaction patterns: pattern matching and allele identification
KR20060012686A (en) 2004-08-04 2006-02-09 한국전자통신연구원 Programmable mask and a method for fabricating biomolecule array using the same
CA2583428A1 (en) * 2004-09-03 2006-03-09 Plexxikon, Inc. Bicyclic heteroaryl pde4b inhibitors
US20060073506A1 (en) 2004-09-17 2006-04-06 Affymetrix, Inc. Methods for identifying biological samples
US20060073511A1 (en) 2004-10-05 2006-04-06 Affymetrix, Inc. Methods for amplifying and analyzing nucleic acids
US7682782B2 (en) 2004-10-29 2010-03-23 Affymetrix, Inc. System, method, and product for multiple wavelength detection using single source excitation
CA2524964A1 (en) 2004-10-29 2006-04-29 Affymetrix, Inc. Automated method of manufacturing polymer arrays
JP4928075B2 (en) * 2004-12-24 2012-05-09 日本曹達株式会社 Organic thin film surface property conversion method
US20060147943A1 (en) * 2004-12-30 2006-07-06 Lewis Mark A Substrates having pendant epoxide groups for binding biomolecules and methods of making and using thereof
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
US8338093B2 (en) * 2004-12-31 2012-12-25 Affymetrix, Inc. Primer array synthesis and validation
US7547775B2 (en) 2004-12-31 2009-06-16 Affymetrix, Inc. Parallel preparation of high fidelity probes in an array format
EP1846760B1 (en) * 2005-01-27 2010-12-15 Quest Diagnostics Investments Incorporated Rapid comparative genome hybridization
US20090038023A1 (en) 2005-03-10 2009-02-05 Verenium Corporation Lyase Enzymes, Nucleic Acids Encoding Them and Methods For Making and Using Them
AU2006227965B2 (en) 2005-03-15 2013-01-31 Bp Corporation North America Inc. Cellulases, nucleic acids encoding them and methods for making and using them
US20080020941A1 (en) 2005-03-24 2008-01-24 Jimpei Tabata Biomolecule-immobilized plate and method for fabricating biomolecule-immobilized plate
EP3770278A1 (en) 2005-04-14 2021-01-27 The Trustees of Boston University Diagnostic for lung disorders using class prediction
JP2008545652A (en) * 2005-05-17 2008-12-18 プレキシコン，インコーポレーテッド Compounds that modulate c-kit and c-fms activity and uses thereof
US8486629B2 (en) 2005-06-01 2013-07-16 Bioarray Solutions, Ltd. Creation of functionalized microparticle libraries by oligonucleotide ligation or elongation
ES2371397T3 (en) * 2005-06-22 2011-12-30 Plexxikon, Inc. PIRROLO DERIVATIVES [2,3-B] PIRIDINE AS INHIBITORS OF PROTEIN KINES.
US20060292559A1 (en) * 2005-06-23 2006-12-28 Beckman Coulter, Inc. Cell-based microarrays, and methods for their preparation and use
WO2007016502A2 (en) 2005-08-02 2007-02-08 Wisconsin Alumni Research Foundation Synthesis of arrays of oligonucleotides and other chain molecules
US20070059742A1 (en) * 2005-09-09 2007-03-15 Stover Axel G Process of stripping a microarray for reuse
US20100233429A1 (en) * 2005-09-16 2010-09-16 Yamatake Corporation Substrate for Biochip, Biochip, Method for Manufacturing Substrate for Biochip and Method for Manufacturing Biochip
US8076074B2 (en) 2005-11-29 2011-12-13 Quest Diagnostics Investments Incorporated Balanced translocation in comparative hybridization
US7634363B2 (en) * 2005-12-07 2009-12-15 Affymetrix, Inc. Methods for high throughput genotyping
US7760274B2 (en) * 2005-12-08 2010-07-20 Electronics And Telecommunications Research Institute Programmable mask for fabricating biomolecule array or polymer array, apparatus for fabricating biomolecule array or polymer array including the programmable mask, and method of fabricating biomolecule array or polymer array using the programmable mask
US7994098B2 (en) * 2005-12-09 2011-08-09 Wisconsin Alumni Research Foundation Light directed DNA synthesis using inverse capping for error reduction
US20070154946A1 (en) 2005-12-29 2007-07-05 Rajasekaran John J Massively parallel synthesis of biopolymeric arrays
US7862996B2 (en) 2005-12-29 2011-01-04 Affymetrix, Inc. Use of acid scavengers for the synthesis of standard length and long-mer nucleic acid arrays
EP1984107A4 (en) * 2006-01-26 2013-12-04 California Inst Of Techn Programming microfluidic devices with molecular information
EP2216403A3 (en) 2006-02-02 2010-11-24 Verenium Corporation Esterases and related nucleic acids and methods
DK1989301T3 (en) 2006-02-10 2015-01-05 Bp Corp North America Inc Cellulolytic enzymes, nucleic acids encoding them, and methods for making and using them
CA2638801C (en) 2006-02-14 2016-12-13 Verenium Corporation Xylanases, nucleic acids encoding them and methods for making and using them
EA019971B1 (en) 2006-03-07 2014-07-30 Верениум Корпорейшн Aldolases, nucleic acids encoding them and methods for making and using them
MX2008011477A (en) 2006-03-07 2008-09-23 Cargill Inc Aldolases, nucleic acids encoding them and methods for making and using them.
EP2605018A1 (en) 2006-03-09 2013-06-19 The Trustees of the Boston University Diagnostic and prognostic methods for lung disorders using gene expression profiles from nose epithelial cells
WO2008118167A1 (en) * 2006-03-24 2008-10-02 The Regents Of The University Of Michigan Method for forming molecular sequences on surfaces
US20070232556A1 (en) * 2006-03-31 2007-10-04 Montine Thomas J Methods and compositions for the treatment of neurological diseases and disorders
CN103397043A (en) 2006-08-04 2013-11-20 维莱尼姆公司 Glucanases, nucleic acids encoding same and method for making and using same
JP5244103B2 (en) 2006-08-09 2013-07-24 ホームステッド クリニカル コーポレイション Organ-specific protein and method of use thereof
DK2617814T3 (en) 2006-09-21 2016-02-22 Basf Enzymes Llc Phytases, nucleic acids encoding them, and methods of producing and using them
CA2663001A1 (en) 2006-09-21 2008-03-27 Verenium Corporation Phospholipases, nucleic acids encoding them and methods for making and using them
US9845494B2 (en) 2006-10-18 2017-12-19 Affymetrix, Inc. Enzymatic methods for genotyping on arrays
CN101548186A (en) 2006-10-24 2009-09-30 皇家飞利浦电子股份有限公司 Detecting target molecules in a sample
US8618248B2 (en) 2006-10-31 2013-12-31 President And Fellows Of Harvard College Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides
WO2008063888A2 (en) 2006-11-22 2008-05-29 Plexxikon, Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US8293684B2 (en) * 2006-11-29 2012-10-23 Exiqon Locked nucleic acid reagents for labelling nucleic acids
US7622295B2 (en) 2006-12-19 2009-11-24 Edelmira Cabezas Molecular microarrays and helical peptides
WO2008079909A1 (en) * 2006-12-21 2008-07-03 Plexxikon, Inc. Pyrrolo [2,3-b] pyridines as kinase modulators
PE20121126A1 (en) * 2006-12-21 2012-08-24 Plexxikon Inc PIRROLO [2,3-B] PYRIDINES COMPOUNDS AS KINASE MODULATORS
EP2479267B1 (en) 2006-12-21 2016-12-21 BASF Enzymes LLC Amylases and glucoamylases, nucleic acids encoding them and methods for making and using them
WO2008080015A2 (en) 2006-12-21 2008-07-03 Plexxikon, Inc. Compounds and methods for kinase modulation, and indications therefor
AR065544A1 (en) 2007-01-30 2009-06-17 Verenium Corp ENZYMES FOR THE TREATMENT OF NUCLEIC ACID LIGNOCELLULOSICS THAT CODE AND METHODS TO PREPARE AND USE THEM
KR100827449B1 (en) 2007-02-07 2008-05-07 삼성전자주식회사 Photolabile compound, oligomer probe array and substrate for oligomer probe array with the same and the method of fabricating the same
JP4850855B2 (en) * 2007-03-22 2012-01-11 信越化学工業株式会社 Manufacturing method of substrate for producing microarray
JP4850854B2 (en) * 2007-03-22 2012-01-11 信越化学工業株式会社 Manufacturing method of substrate for producing microarray
US7572990B2 (en) * 2007-03-30 2009-08-11 Intermec Ip Corp. Keypad overlay membrane
CA3017478A1 (en) 2007-04-27 2008-11-06 The Regents Of The University Of California Plant co2 sensors, nucleic acids encoding them, and methods for making and using them
US8200440B2 (en) 2007-05-18 2012-06-12 Affymetrix, Inc. System, method, and computer software product for genotype determination using probe array data
DK2170776T3 (en) 2007-06-28 2019-02-25 Prime Synthesis Inc Process for preparing a polymer coated glass particle with controlled porosity
AU2008276063B2 (en) 2007-07-17 2013-11-28 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US7507539B2 (en) * 2007-07-30 2009-03-24 Quest Diagnostics Investments Incorporated Substractive single label comparative hybridization
WO2009039208A1 (en) * 2007-09-17 2009-03-26 Twof, Inc. Supramolecular nanostamping printing device
KR101387633B1 (en) * 2007-10-02 2014-04-22 삼성전자 주식회사 Binary-coupled type probe array, biochip, and fabricating method of the same
MX2010003600A (en) 2007-10-03 2010-12-14 Verenium Corp Xylanases, nucleic acids encoding them and methods for making and using them.
US8709772B2 (en) 2008-01-03 2014-04-29 Verenium Corporation Transferases and oxidoreductases, nucleic acids encoding them and methods for making and using them
EP2253713B1 (en) 2008-03-11 2015-02-25 National Cancer Center Method for measuring chromosome, gene or specific nucleotide sequence copy numbers using snp array
EP2107125A1 (en) 2008-03-31 2009-10-07 Eppendorf Array Technologies SA (EAT) Real-time PCR of targets on a micro-array
WO2009126900A1 (en) 2008-04-11 2009-10-15 Pelikan Technologies, Inc. Method and apparatus for analyte detecting device
US20110118125A1 (en) * 2008-05-03 2011-05-19 Tufts Medical Center, Inc. Neonatal salivary genomics
EP2145895B1 (en) 2008-07-08 2013-10-30 Commissariat à l'Énergie Atomique et aux Énergies Alternatives Process for the manufacturing of glycochips
US8198062B2 (en) 2008-08-29 2012-06-12 Dsm Ip Assets B.V. Hydrolases, nucleic acids encoding them and methods for making and using them
US8153391B2 (en) 2008-08-29 2012-04-10 Bunge Oils, Inc. Hydrolases, nucleic acids encoding them and methods for making and using them
CA2734519C (en) 2008-08-29 2018-11-13 Centocor Ortho Biotech Inc. Markers and methods for assessing and treating ulcerative colitis and related disorders using a 20 gene panel
US8357503B2 (en) 2008-08-29 2013-01-22 Bunge Oils, Inc. Hydrolases, nucleic acids encoding them and methods for making and using them
WO2010054195A2 (en) 2008-11-07 2010-05-14 Centocor Ortho Biotech Inc. Markers and methods for assessing and treating lupus patients susceptible to photoprovocation
US9375169B2 (en) 2009-01-30 2016-06-28 Sanofi-Aventis Deutschland Gmbh Cam drive for managing disposable penetrating member actions with a single motor and motor and control system
JP2012517238A (en) 2009-02-11 2012-08-02 カリス エムピーアイ インコーポレイテッド Molecular profiling of tumors
DK2406399T3 (en) * 2009-03-09 2018-03-12 Bioatla Llc MIRAC PROTEINS
AR078033A1 (en) 2009-04-03 2011-10-12 Plexxikon Inc A SOLID DISPERSION, CONTAINING THE COMPOUND {3- [5- (4- (CHLORINE-PHENYL) -1H-PIRROLO [2,3-B] PIRIDINA-3-CARBONIL] -2,4-DIFLUOR-PHENIL} -AMIDA OF PROPANE-1-SULPHONIC ACID, COMPOSITIONS AND FORMULATIONS THAT INCLUDE SUCH SOLID DISPERSION; METHODS FOR MANUFACTURING SUCH SOLID DISPERSION, FORMS 1 AND 2
NZ596459A (en) 2009-05-21 2013-11-29 Verenium Corp Phytases, nucleic acids encoding them and methods for making and using them
US20100298171A1 (en) * 2009-05-22 2010-11-25 Affymetrix, Inc. Apparatus for polymer synthesis
US8329724B2 (en) 2009-08-03 2012-12-11 Hoffmann-La Roche Inc. Process for the manufacture of pharmaceutically active compounds
AU2010298000A1 (en) 2009-09-25 2012-04-05 Signature Genomics Laboratories Llc Multiplex (+/-) stranded arrays and assays for detecting chromosomal abnormalities associated with cancer and other diseases
UA111708C2 (en) 2009-10-16 2016-06-10 Бандж Ойлз, Інк. METHOD OF OIL REFINING
UA109884C2 (en) 2009-10-16 2015-10-26 A POLYPEPTIDE THAT HAS THE ACTIVITY OF THE PHOSPHATIDYLINOSYTOL-SPECIFIC PHOSPHOLIPASE C, NUCLEIC ACID, AND METHOD OF METHOD
US20120322677A1 (en) 2009-10-19 2012-12-20 Stichting Het Nederlands Kanker Instituut Predicting benefit of anti-cancer therapy via array comparative genomic hybridization
EP2491140A1 (en) 2009-10-19 2012-08-29 Stichting Het Nederlands Kanker Instituut Predicting response to anti-cancer therapy via array comparative genomic hybridization
US20120316080A1 (en) 2009-10-19 2012-12-13 Stichting Het Nederlands Kanker Instiuut Differentiation between brca2-associated tumours and sporadic tumours via array comparative genomic hybridization
WO2011056688A2 (en) 2009-10-27 2011-05-12 Caris Life Sciences, Inc. Molecular profiling for personalized medicine
NZ599866A (en) 2009-11-06 2014-09-26 Plexxikon Inc Compounds and methods for kinase modulation, and indications therefor
US8501122B2 (en) 2009-12-08 2013-08-06 Affymetrix, Inc. Manufacturing and processing polymer arrays
US8835358B2 (en) 2009-12-15 2014-09-16 Cellular Research, Inc. Digital counting of individual molecules by stochastic attachment of diverse labels
US20110143966A1 (en) * 2009-12-15 2011-06-16 Affymetrix, Inc. Surface Modifications and Methods for their Synthesis and Use
US10787701B2 (en) 2010-04-05 2020-09-29 Prognosys Biosciences, Inc. Spatially encoded biological assays
US20190300945A1 (en) 2010-04-05 2019-10-03 Prognosys Biosciences, Inc. Spatially Encoded Biological Assays
WO2011127099A1 (en) 2010-04-05 2011-10-13 Prognosys Biosciences, Inc. Spatially encoded biological assays
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
WO2012038837A2 (en) 2010-09-20 2012-03-29 Stichting Het Nederlands Kanker Instituut Methods for predicting response to anti-cancer therapy in cancer patients
CA2811789A1 (en) 2010-10-06 2012-04-12 Bp Corporation North America Inc. Variant cbh i polypeptides with reduced product inhibition
PE20141360A1 (en) 2011-02-07 2014-10-13 Plexxikon Inc COMPOUNDS AND METHODS FOR THE MODULATION OF KINASES AND INDICATIONS FOR THEM.
TWI558702B (en) 2011-02-21 2016-11-21 普雷辛肯公司 Solid forms of a pharmaceutically active substance
US8759036B2 (en) 2011-03-21 2014-06-24 Affymetrix, Inc. Methods for synthesizing pools of probes
GB201106254D0 (en) 2011-04-13 2011-05-25 Frisen Jonas Method and product
RU2631487C2 (en) 2011-05-17 2017-09-22 Плексксикон Инк. Kinases modulation and indications for its use
US8960686B2 (en) * 2011-09-30 2015-02-24 Electro Scientific Industries, Inc. Controlled surface roughness in vacuum retention
CA2865575C (en) 2012-02-27 2024-01-16 Cellular Research, Inc. Compositions and kits for molecular counting
US11177020B2 (en) 2012-02-27 2021-11-16 The University Of North Carolina At Chapel Hill Methods and uses for molecular tags
US9150570B2 (en) 2012-05-31 2015-10-06 Plexxikon Inc. Synthesis of heterocyclic compounds
EP2722105A1 (en) * 2012-10-22 2014-04-23 Universität Wien Method of in situ synthesizing microarrays
KR101709424B1 (en) * 2012-11-15 2017-02-22 제임스 앤드류 레스코세크 Plasma gate
US9267171B2 (en) 2013-02-28 2016-02-23 New York University DNA photolithography with cinnamate crosslinkers
US10535420B2 (en) 2013-03-15 2020-01-14 Affymetrix, Inc. Systems and methods for probe design to detect the presence of simple and complex indels
KR102126275B1 (en) 2013-05-03 2020-06-25 삼성디스플레이 주식회사 Apparatus for aligning a substrate and appratus for cutting a substrate using the same
WO2014210225A1 (en) 2013-06-25 2014-12-31 Prognosys Biosciences, Inc. Methods and systems for determining spatial patterns of biological targets in a sample
AU2014312208B2 (en) 2013-08-28 2019-07-25 Becton, Dickinson And Company Massively parallel single cell analysis
KR20150078515A (en) * 2013-12-31 2015-07-08 삼성디스플레이 주식회사 Measuring method for reaction ratio of reactive mesogen
US9387451B2 (en) 2014-02-03 2016-07-12 International Business Machines Corporation Flow cell array and uses thereof
WO2015175375A1 (en) 2014-05-13 2015-11-19 Short Jay M Conditionally active biological proteins
EP3146094B1 (en) 2014-05-23 2019-08-28 Centrillion Technology Holdings Corporation Oligonucleotide probe inversion process for in situ synthesized probe arrays
US11111288B2 (en) 2014-08-28 2021-09-07 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified t-cells
RU2764074C2 (en) 2014-08-28 2022-01-13 Байоатла, Ллк Conditionally active chimeric antigen receptors for modified t-cells
US10513699B2 (en) 2014-09-03 2019-12-24 Bioatla, Llc Discovering and producing conditionally active biologic proteins in the same eukaryotic cell production hosts
US10801065B2 (en) 2015-02-10 2020-10-13 Dana-Farber Cancer Institute, Inc. Methods of determining levels of exposure to radiation and uses thereof
AU2016222830B2 (en) 2015-02-24 2021-02-25 Bioatla Llc Conditionally active biological proteins
WO2016164641A1 (en) 2015-04-08 2016-10-13 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
EP3530752B1 (en) 2015-04-10 2021-03-24 Spatial Transcriptomics AB Spatially distinguished, multiplex nucleic acid analysis of biological specimens
US10829484B2 (en) 2015-07-28 2020-11-10 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
EP3130682B1 (en) * 2015-08-13 2020-03-18 Centrillion Technology Holdings Corporation Methods for generating polymer arrays
US10695735B2 (en) 2015-08-18 2020-06-30 Centrillion Technology Holdings Corporation Probe inversion process for in situ synthesized probe arrays
US20180305748A1 (en) 2015-10-18 2018-10-25 Affymetrix, Inc. Multiallelic Genotyping of Single Nucleotide Polymorphisms and Indels
CA3007462C (en) 2015-12-07 2023-10-24 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
RS63698B1 (en) 2016-05-13 2022-11-30 Bioatla Inc Anti-ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof
TW201815766A (en) 2016-09-22 2018-05-01 美商普雷辛肯公司 Compounds and methods for IDO and TDO modulation, and indications therefor
CA3047580A1 (en) 2016-12-23 2018-07-26 Plexxikon Inc. Compounds and methods for cdk8 modulation and indications therefor
US10428067B2 (en) 2017-06-07 2019-10-01 Plexxikon Inc. Compounds and methods for kinase modulation
EP3802847A4 (en) * 2018-05-29 2022-03-09 Centrillion Technologies, Inc. Increasing efficiency of photochemical reactions on substrates
MX2021006234A (en) 2018-11-30 2021-09-10 Caris Mpi Inc Next-generation molecular profiling.
US11649485B2 (en) 2019-01-06 2023-05-16 10X Genomics, Inc. Generating capture probes for spatial analysis
US11926867B2 (en) 2019-01-06 2024-03-12 10X Genomics, Inc. Generating capture probes for spatial analysis
IL293489A (en) 2019-12-02 2022-08-01 Caris Mpi Inc Pan-cancer platinum response predictor
US11821035B1 (en) 2020-01-29 2023-11-21 10X Genomics, Inc. Compositions and methods of making gene expression libraries

Family Cites Families (123)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6112373B2 (en) * 1974-09-04 1986-04-08 Hitachi Ltd
US4180739A (en) 1977-12-23 1979-12-25 Varian Associates, Inc. Thermostatable flow cell for fluorescence measurements
US4294800A (en) 1978-10-30 1981-10-13 Tavlarides Lawrence L Liquid jet recycle reactor
US4500707A (en) * 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4458066A (en) * 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4401796A (en) * 1981-04-30 1983-08-30 City Of Hope Research Institute Solid-phase synthesis of polynucleotides
US4507433A (en) * 1983-10-07 1985-03-26 The Johns Hopkins University Preparation of oligodeoxyribonucleoside alkyl or arylphosphonates
DE3565986D1 (en) * 1984-05-02 1988-12-08 Brendan James Hamill An apparatus for the chemical synthesis of oligonucleotides
CA1231136A (en) * 1984-06-13 1988-01-05 Ian A. Shanks Capillary action chemical test device
JPS61231716A (en) * 1985-04-08 1986-10-16 Hitachi Ltd Filming apparatus
US4751170A (en) * 1985-07-26 1988-06-14 Nippon Telegraph And Telephone Corporation Silylation method onto surface of polymer membrane and pattern formation process by the utilization of silylation method
US4963245A (en) 1986-05-02 1990-10-16 Ciba Corning Diagnostics Corp. Unitary multiple electrode sensor
US5175209A (en) 1987-01-06 1992-12-29 Baylor College Of Medicine Porous wafer for segmented synthesis of biopolymers
US5525464A (en) 1987-04-01 1996-06-11 Hyseq, Inc. Method of sequencing by hybridization of oligonucleotide probes
US5202231A (en) 1987-04-01 1993-04-13 Drmanac Radoje T Method of sequencing of genomes by hybridization of oligonucleotide probes
US5100775A (en) * 1988-03-16 1992-03-31 Smyczek Peter J Method for conducting nucleic acid hybridization in chamber with precise fluid delivery
US5700637A (en) 1988-05-03 1997-12-23 Isis Innovation Limited Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays
US5188963A (en) * 1989-11-17 1993-02-23 Gene Tec Corporation Device for processing biological specimens for analysis of nucleic acids
GB8827853D0 (en) * 1988-11-29 1988-12-29 Ares Serono Res & Dev Ltd Sensor for optical assay
US5547839A (en) * 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
US5424186A (en) * 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
US6955915B2 (en) 1989-06-07 2005-10-18 Affymetrix, Inc. Apparatus comprising polymers
US5527681A (en) * 1989-06-07 1996-06-18 Affymax Technologies N.V. Immobilized molecular synthesis of systematically substituted compounds
US5242974A (en) * 1991-11-22 1993-09-07 Affymax Technologies N.V. Polymer reversal on solid surfaces
US5143854A (en) * 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5744101A (en) * 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US5595707A (en) * 1990-03-02 1997-01-21 Ventana Medical Systems, Inc. Automated biological reaction apparatus
US5723289A (en) * 1990-06-11 1998-03-03 Nexstar Pharmaceuticals, Inc. Parallel selex
ATE244065T1 (en) * 1990-12-06 2003-07-15 Affymetrix Inc METHODS AND REAGENTS FOR VERY LARGE SCALE IMMOBILIZED POLYMER SYNTHESIS
US5449754A (en) 1991-08-07 1995-09-12 H & N Instruments, Inc. Generation of combinatorial libraries
WO1993002992A1 (en) 1991-08-07 1993-02-18 H & N Instruments, Inc. Synthesis of chain chemical compounds
US5187096A (en) 1991-08-08 1993-02-16 Rensselaer Polytechnic Institute Cell substrate electrical impedance sensor with multiple electrode array
US5639603A (en) * 1991-09-18 1997-06-17 Affymax Technologies N.V. Synthesizing and screening molecular diversity
IL103674A0 (en) * 1991-11-19 1993-04-04 Houston Advanced Res Center Method and apparatus for molecule detection
US5846708A (en) * 1991-11-19 1998-12-08 Massachusetts Institiute Of Technology Optical and electrical methods and apparatus for molecule detection
US5324633A (en) * 1991-11-22 1994-06-28 Affymax Technologies N.V. Method and apparatus for measuring binding affinity
US5384261A (en) * 1991-11-22 1995-01-24 Affymax Technologies N.V. Very large scale immobilized polymer synthesis using mechanically directed flow paths
CA2124087C (en) * 1991-11-22 2002-10-01 James L. Winkler Combinatorial strategies for polymer synthesis
US5288514A (en) * 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
US5324483B1 (en) * 1992-10-08 1996-09-24 Warner Lambert Co Apparatus for multiple simultaneous synthesis
AU5449094A (en) * 1992-11-02 1994-05-24 Affymax Technologies N.V. Novel photoreactive protecting groups
US5679548A (en) 1993-02-02 1997-10-21 The Scripps Research Institute Methods for producing polypeptide metal binding sites and compositions thereof
ES2119166T3 (en) 1993-02-03 1998-10-01 Histaggen Inc AUTOMATIC HISTOCYTOCHEMICAL ENCAPSULATION SYSTEM AND APPARATUS INTENDED FOR THE TREATMENT OF BIOLOGICAL SUBSTANCES.
US5368823A (en) 1993-02-11 1994-11-29 University Of Georgia Research Foundation, Inc. Automated synthesis of oligonucleotides
US5534328A (en) * 1993-12-02 1996-07-09 E. I. Du Pont De Nemours And Company Integrated chemical processing apparatus and processes for the preparation thereof
DE69431719T2 (en) * 1993-06-25 2003-09-18 Affymetrix Inc N D Ges D Staat HYBRIDIZATION AND SEQUENCING OF NUCLEIC ACIDS
US5837832A (en) 1993-06-25 1998-11-17 Affymetrix, Inc. Arrays of nucleic acid probes on biological chips
US5472672A (en) 1993-10-22 1995-12-05 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and method for polymer synthesis using arrays
US6165778A (en) 1993-11-02 2000-12-26 Affymax Technologies N.V. Reaction vessel agitation apparatus
US5631734A (en) * 1994-02-10 1997-05-20 Affymetrix, Inc. Method and apparatus for detection of fluorescently labeled materials
US6015880A (en) 1994-03-16 2000-01-18 California Institute Of Technology Method and substrate for performing multiple sequential reactions on a matrix
DE69527585T2 (en) * 1994-06-08 2003-04-03 Affymetrix Inc Method and device for packaging chips
US6287850B1 (en) * 1995-06-07 2001-09-11 Affymetrix, Inc. Bioarray chip reaction apparatus and its manufacture
US5508197A (en) * 1994-07-25 1996-04-16 The Regents, University Of California High-speed thermal cycling system and method of use
US5609305A (en) * 1994-09-19 1997-03-11 Vortec Corporation Apparatus for providing an air curtain
US5985356A (en) 1994-10-18 1999-11-16 The Regents Of The University Of California Combinatorial synthesis of novel materials
US5556752A (en) * 1994-10-24 1996-09-17 Affymetrix, Inc. Surface-bound, unimolecular, double-stranded DNA
AU705351B2 (en) 1994-11-10 1999-05-20 Orchid Biosciences, Inc. Liquid distribution system
US5659477A (en) * 1994-12-28 1997-08-19 Collins; Charles Michael Self reproducing fundamental fabricating machines (F-Units)
EP0843169B1 (en) 1995-02-25 2003-03-19 Roche Diagnostics GmbH Device for treating samples on microscope slides
US5599695A (en) 1995-02-27 1997-02-04 Affymetrix, Inc. Printing molecular library arrays using deprotection agents solely in the vapor phase
US5959098A (en) 1996-04-17 1999-09-28 Affymetrix, Inc. Substrate preparation process
US6239273B1 (en) 1995-02-27 2001-05-29 Affymetrix, Inc. Printing molecular library arrays
GB9506312D0 (en) * 1995-03-28 1995-05-17 Medical Res Council Improvements in or relating to sample processing
US5624711A (en) * 1995-04-27 1997-04-29 Affymax Technologies, N.V. Derivatization of solid supports and methods for oligomer synthesis
US5545531A (en) * 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US5856174A (en) * 1995-06-29 1999-01-05 Affymetrix, Inc. Integrated nucleic acid diagnostic device
US6168948B1 (en) * 1995-06-29 2001-01-02 Affymetrix, Inc. Miniaturized genetic analysis systems and methods
US5888830A (en) * 1995-09-22 1999-03-30 Berlex Laboratories, Inc. Apparatus and process for multiple chemical reactions
US6132580A (en) 1995-09-28 2000-10-17 The Regents Of The University Of California Miniature reaction chamber and devices incorporating same
US6660233B1 (en) 1996-01-16 2003-12-09 Beckman Coulter, Inc. Analytical biochemistry system with robotically carried bioarray
US6140133A (en) 1996-01-23 2000-10-31 Novartis Ag Device and process for synthesizing macromolecules
US6114122A (en) * 1996-03-26 2000-09-05 Affymetrix, Inc. Fluidics station with a mounting system and method of using
US6706875B1 (en) * 1996-04-17 2004-03-16 Affyemtrix, Inc. Substrate preparation process
US5958342A (en) * 1996-05-17 1999-09-28 Incyte Pharmaceuticals, Inc. Jet droplet device
AU3568897A (en) * 1996-06-07 1998-01-05 Eos Biotechnology, Inc. Immobilised linear oligonucleotide arrays
FR2749663B1 (en) * 1996-06-07 1998-07-31 Bio Merieux SINGLE USE ANALYSIS CARD COMPRISING A LIQUID FLOW CONDUIT
US5981733A (en) 1996-09-16 1999-11-09 Incyte Pharmaceuticals, Inc. Apparatus for the chemical synthesis of molecular arrays
US6720186B1 (en) * 1998-04-03 2004-04-13 Symyx Technologies, Inc. Method of research for creating and testing novel catalysts, reactions and polymers
US6541271B1 (en) * 1996-10-09 2003-04-01 Symyx Technologies, Inc. Infrared spectroscopic imaging of libraries
US6001311A (en) 1997-02-05 1999-12-14 Protogene Laboratories, Inc. Apparatus for diverse chemical synthesis using two-dimensional array
US6544775B2 (en) * 1997-02-21 2003-04-08 Merckle Gmbh Automated macromolecule synthesizing process and device
US6126904A (en) 1997-03-07 2000-10-03 Argonaut Technologies, Inc. Apparatus and methods for the preparation of chemical compounds
JP2001518086A (en) * 1997-03-20 2001-10-09 ユニバーシティ オブ ワシントン Solvents, solvent microdroplets, and methods of use for biopolymer synthesis
JP3270730B2 (en) * 1997-03-21 2002-04-02 株式会社日立国際電気 Substrate processing apparatus and substrate processing method
US6420108B2 (en) * 1998-02-09 2002-07-16 Affymetrix, Inc. Computer-aided display for comparative gene expression
US5814365A (en) * 1997-08-15 1998-09-29 Micro C Technologies, Inc. Reactor and method of processing a semiconductor substate
JP3498201B2 (en) 1997-08-27 2004-02-16 アークレイ株式会社 Vacuum generator and sample analyzer using the same
US6150147A (en) 1998-02-06 2000-11-21 Affymetrix, Inc. Biological array fabrication methods with reduction of static charge
US6165069A (en) 1998-03-11 2000-12-26 Digideal Corporation Automated system for playing live casino table games having tabletop changeable playing card displays and monitoring security features
US6251595B1 (en) * 1998-06-18 2001-06-26 Agilent Technologies, Inc. Methods and devices for carrying out chemical reactions
EP0977240A1 (en) 1998-07-30 2000-02-02 IMEC vzw System, method and apparatus for processing semiconductors
US6461812B2 (en) * 1998-09-09 2002-10-08 Agilent Technologies, Inc. Method and multiple reservoir apparatus for fabrication of biomolecular arrays
DE19846749C2 (en) * 1998-10-12 2000-10-12 Junker Gmbh O Aerodynamic sealing of continuous heat treatment plants with a protective gas atmosphere
CA2255850C (en) * 1998-12-07 2000-10-17 Her Majesty The Queen In Right Of Canada As Represented By The Minister Of Agriculture And Agri-Food Rotary thermocycling apparatus
EP1024200A2 (en) 1999-01-27 2000-08-02 Affymetrix, Inc. (a California Corporation) Genetic compositions and methods
US6749814B1 (en) * 1999-03-03 2004-06-15 Symyx Technologies, Inc. Chemical processing microsystems comprising parallel flow microreactors and methods for using same
US6323043B1 (en) 1999-04-30 2001-11-27 Agilent Technologies, Inc. Fabricating biopolymer arrays
US6242266B1 (en) * 1999-04-30 2001-06-05 Agilent Technologies Inc. Preparation of biopolymer arrays
US6258593B1 (en) * 1999-06-30 2001-07-10 Agilent Technologies Inc. Apparatus for conducting chemical or biochemical reactions on a solid surface within an enclosed chamber
US6306599B1 (en) 1999-07-16 2001-10-23 Agilent Technologies Inc. Biopolymer arrays and their fabrication
US6180351B1 (en) * 1999-07-22 2001-01-30 Agilent Technologies Inc. Chemical array fabrication with identifier
US6232072B1 (en) * 1999-10-15 2001-05-15 Agilent Technologies, Inc. Biopolymer array inspection
US6440669B1 (en) * 1999-11-10 2002-08-27 Agilent Technologies, Inc. Methods for applying small volumes of reagents
NO310385B1 (en) * 1999-11-17 2001-06-25 Torstein Ljungmann Device for automatic adhesion of cover glass to slides
JP3723712B2 (en) * 2000-02-10 2005-12-07 株式会社日立国際電気 Substrate processing apparatus and substrate processing method
JP2001267991A (en) 2000-03-16 2001-09-28 Sony Corp Transmitter, transmission method, communication system and communication method
US6599693B1 (en) * 2000-07-31 2003-07-29 Agilent Technologies Inc. Array fabrication
US6613893B1 (en) 2000-07-31 2003-09-02 Agilent Technologies Inc. Array fabrication
US6656740B1 (en) 2000-10-31 2003-12-02 Agilent Technologies, Inc. Pressure variation in array fabrication
US6484104B2 (en) * 2001-02-15 2002-11-19 Klaus Abraham-Fuchs Network for evaluating data obtained in a biochip measurement device
US6867050B2 (en) * 2001-05-16 2005-03-15 Academia Sinica Apparatus and methods for chemical synthesis
US6713023B2 (en) 2001-06-29 2004-03-30 Agilent Technologies, Inc. Flow cell for chemical reactions
US6649348B2 (en) * 2001-06-29 2003-11-18 Agilent Technologies Inc. Methods for manufacturing arrays
US6696298B2 (en) * 2001-12-07 2004-02-24 Biosearch Technologies, Inc. Multi-channel reagent dispensing apparatus
US6935727B2 (en) * 2001-12-18 2005-08-30 Agilent Technologies, Inc. Pulse jet print head assembly having multiple reservoirs and methods for use in the manufacture of biopolymeric arrays
US6790620B2 (en) * 2001-12-24 2004-09-14 Agilent Technologies, Inc. Small volume chambers
US20030143329A1 (en) * 2002-01-30 2003-07-31 Shchegrova Svetlana V. Error correction in array fabrication
US7141368B2 (en) * 2002-01-30 2006-11-28 Agilent Technologies, Inc. Multi-directional deposition in array fabrication
EP1573056A4 (en) * 2002-05-17 2007-11-28 Nugen Technologies Inc Methods for fragmentation, labeling and immobilization of nucleic acids
US20030232140A1 (en) 2002-06-14 2003-12-18 Joseph Remick Methods for reagent removal in flow chambers
US7332273B2 (en) 2002-06-20 2008-02-19 Affymetrix, Inc. Antireflective coatings for high-resolution photolithographic synthesis of DNA arrays
US20040009608A1 (en) * 2002-07-10 2004-01-15 Caren Michael P. Arrays with positioning control

Also Published As

Publication number Publication date
US8309496B2 (en) 2012-11-13
AU2804797A (en) 1997-11-07
US6307042B1 (en) 2001-10-23
CA2251755C (en) 2010-09-14
JP2006258806A (en) 2006-09-28
US8067578B2 (en) 2011-11-29
US20130059763A1 (en) 2013-03-07
US8637434B2 (en) 2014-01-28
EP0950112A1 (en) 1999-10-20
US20120071361A1 (en) 2012-03-22
JP2000508542A (en) 2000-07-11
WO1997039151A1 (en) 1997-10-23
US5959098A (en) 1999-09-28
US20100331217A1 (en) 2010-12-30
EP0950112A4 (en) 2004-12-15
US20090062148A1 (en) 2009-03-05

Similar Documents

Publication Publication Date Title
CA2251755A1 (en) Photolabile polymer array synthesis methods
US6887665B2 (en) Methods of array synthesis
EP0946286B1 (en) Chemical amplification for the synthesis of patterned arrays
EP1956028B1 (en) Photolabile compound, oligomer probe array and substrate for oligomer probe array containing the same, and manufacturing method of the same
US6300137B1 (en) Method for synthesizing a specific, surface-bound polymer uniformly over an element of a molecular array
US5658734A (en) Process for synthesizing chemical compounds
CN101473220B (en) Electrode array device having an adsorbed porous reaction layer
JP2004144768A5 (en)
CN101156062B (en) Electrode array device having an adsorbed porous reaction layer having a linker moiety
US20080213694A1 (en) Composition containing a photoacid generator monomer, substrat coated with the composition, method for synthesizing a compound on a substrate using the composition, and microarray produced according to the method
WO1994010128A1 (en) Novel photoreactive protecting groups
CN101221121B (en) Method of fabricating microarray
US20050101765A1 (en) Photocleavable protecting groups
US20110201528A1 (en) Methods Of Forming An Oligomer Array
McGall et al. Photolithographic synthesis of high-density oligonucleotide arrays
KR100791335B1 (en) Microarray and method of fabricating the same
US6184347B1 (en) Minimization of blooming in high-density arrays by using reactive wash reagents
Xiao et al. DNA microarray synthesis by using PDMS molecular stamp (II) Oligonucleotide on-chip synthesis using PDMS stamp
US20100056397A1 (en) Method of Producing Microarray Having Immobilized Double-Stranded Nucleic Acid Probe Including Double-Stranded Region and Single-Stranded Region
KR20110111720A (en) Method of fabricating microarray
EP1958690A1 (en) Substrate structure, oligomer probe array and methods for producing the same
KR100801080B1 (en) Photolabile compound and substrate for oligomer probe array with the same
CN110922441B (en) Linking matrix for light-oriented microarray DNA synthesis and synthesis method
WO2007081664A2 (en) Use of acid scavengers for the synthesis of standard length and long-mer nucleic acid arrays
KR20110135752A (en) Photoresist composirion for fabricating probe array and method of fabricating probe array using thereby

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20170418