CA2374735A1 - Encoding and decoding of array sensors utilizing nanocrystals - Google Patents

Encoding and decoding of array sensors utilizing nanocrystals Download PDF

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Publication number
CA2374735A1
CA2374735A1 CA002374735A CA2374735A CA2374735A1 CA 2374735 A1 CA2374735 A1 CA 2374735A1 CA 002374735 A CA002374735 A CA 002374735A CA 2374735 A CA2374735 A CA 2374735A CA 2374735 A1 CA2374735 A1 CA 2374735A1
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nanocrystal
microspheres
subpopulation
composition
bioactive agent
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CA2374735C (en
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Mark S. Chee
Steven M. Barnard
Chanfeng Zhao
Anthony W. Czarnik
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Illumina Inc
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
    • G01N33/587—Nanoparticles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/588—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with semiconductor nanocrystal label, e.g. quantum dots
    • 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
    • Y10S436/805—Optical property
    • 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
    • Y10S436/823—Immunogenic carrier or carrier per se
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/773—Nanoparticle, i.e. structure having three dimensions of 100 nm or less
    • Y10S977/775—Nanosized powder or flake, e.g. nanosized catalyst
    • Y10S977/776—Ceramic powder or flake
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/788—Of specified organic or carbon-based composition
    • Y10S977/789—Of specified organic or carbon-based composition in array format
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/788—Of specified organic or carbon-based composition
    • Y10S977/789—Of specified organic or carbon-based composition in array format
    • Y10S977/79—Of specified organic or carbon-based composition in array format with heterogeneous nanostructures
    • Y10S977/791—Molecular array
    • Y10S977/792—Nucleic acid array, e.g. human genome array
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/788—Of specified organic or carbon-based composition
    • Y10S977/795—Composed of biological material
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/84—Manufacture, treatment, or detection of nanostructure
    • Y10S977/895—Manufacture, treatment, or detection of nanostructure having step or means utilizing chemical property
    • Y10S977/896—Chemical synthesis, e.g. chemical bonding or breaking
    • Y10S977/898—Enzymatic
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • 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
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • Y10S977/915—Therapeutic or pharmaceutical composition

Abstract

Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

Claims (40)

1. A composition comprising:
a) a substrate with a surface comprising discrete sites; and b) a population of microspheres distributed on said sites, wherein at least one of said microspheres comprises a nanocrystal.
2. A composition according to claim 1 wherein said nanocrystal is embedded in said microsphere.
3. A composition according to claim 2 wherein said nanocrystal is sealed into porous silica microsphere using the sol-gel polymerization process.
4. A composition according to claim 1 wherein said nanocrystal is attached to said microsphere.
5. A composition according to claim 1 wherein said microsphere comprising said nanocrystal further comprises at least one additional nanocrystal.
6. A composition according to claim 1 wherein at least a plurality of said microspheres comprises a nanocrystal.
7. A composition according to claim 1 wherein at least two microspheres comprise an optical signature which differ from one another.
8. A composition according to claim 7 wherein said two microspheres each comprise a nanocrystal and wherein said nanocrystals differ in size from one another.
9. A composition according to claim 1 wherein said microspheres comprise bioactive agents.
10. A composition according to claim 9 wherein said bioactive agents comprise nucleic acids.
11. A composition according to claim 9 wherein said bioactive agents comprise proteins.
12. A composition according to claim 11 wherein said proteins are selected from the group consisting of enzymes and antibodies.
13. A composition according to claim 1 wherein said population of microspheres comprises at least a first and a second subpopulation comprising:
i) a a first and a second bioactive agent, respectively; and ii) a first and a second optical signature, respectively, capable of identifying each bioactive agent, wherein at least one of said optical signatures comprises said nanocrystal.
14. A composition according to claim 13 wherein at least one of said optical signatures comprises at least two nanocrystals.
15. A composition according to claim 13 wherein said first and second optical signatures each comprise a nanocrystal and wherein said nanocrystals differ in size from one another.
16. An array composition comprising:
a) a substrate with a surface comprising discrete sites; and b) a population of microspheres comprising at least a first and a second subpopulation, wherein each subpopulation comprises a bioactive agent bound to a target analyte comprising a nanocrystal, wherein said microspheres are distributed on said surface.
17. An array composition comprising:
a) a substrate with a surface comprising discrete sites; and b) a population of microspheres comprising at least a first and a second subpopulation, wherein each subpopulation comprises:

i) a bioactive agent; and ii) an identifier binding ligand bound to a decoder binding ligand comprising a nanocrystal such that the identification of the bioactive agent can be elucidated;
wherein said microspheres are distributed on said surface.
18. An array composition comprising:
a) a substrate with a surface comprising discrete sites; and b) a population of microspheres comprising at least a first and a second subpopulation, wherein each subpopulation comprises a bioactive agent bound to a decoder binding ligand comprising a nanocrystal, wherein said microspheres are distributed on said surface.
19. An array composition according to claim 16, 17 or 18 wherein at least one nanocrystal of said first subpopulation differs in size from a nanocrystal of said second subpopulation.
20. A composition according to claim 16 or 17 wherein said bioactive agents are nucleic acids.
21. A composition according to claim 16 or 17 wherein said bioactive agents are proteins.
22. A method of making a composition comprising:
a) forming a surface comprising individual sites on a substrate;
b) distributing microspheres on said surface such that said individual sites contain microspheres, wherein said microspheres comprise an optical signature, wherein at least one optical signature comprises at least one nanocrystal.
23. A method according to claim 22 wherein at least two optical signatures comprise a nanocrystal, and wherein at least one of said optical signatures comprises a nanocrystal differing in size from a nanocrystal of another optical signature.
24. A method of making a composition comprising:
a) forming a surface comprising individual sites on a substrate;
b) distributing microspheres on said surface such that said individual sites contain microspheres, wherein said microspheres comprise at least a first and a second subpopulation each comprising:
i) a bioactive agent; and ii) an optical signature capable of identifying said bioactive agent, wherein at least one optical signature comprises at least one nanocrystal.
25. A method according to claim 24 wherein at least one nanocrystal of said first subpopulation differs in size from a nanocrystal of said second population.
26. A method according to claim 22 or 24 wherein said nanocrystals are manufactured to have a specific size.
27. A method according to claim 22 or 24 wherein said nanocrystals are manufactured and have a size distribution and then are sorted by size.
28. A method of determining the presence of a target analyte in a sample comprising:
a) contacting said sample with a composition comprising:
i) a substrate with a surface comprising discrete sites; and ii) a population of microspheres comprising at least a first and a second subpopulation each comprising:
1) a bioactive agent; and 2) an optical signature capable of identifying said bioactive agent;
wherein said microspheres are distributed on said surface such that said discrete sites contain microspheres and wherein at least one of said optical signatures comprises at least one nanocrystal; and b) determining the presence or absence of said target analyte.
29. A method according to claim 28 wherein each of said nanocrystals have a size and at least one nanocrystal of said first subpopulation differs in size from a nanocrystal of said second population.
30. A method according to claim 28 further comprising identifying the location of each bioactive agent on said substrate.
31. A method according to claim 30 further comprising identifying the location of each bioactive agent on said substrate by sorting said optical signatures based on said size of said nanocrystals.
32. A method of determining the presence of a target analyte comprising an optical signature comprising at least one nanocrystal in a sample comprising:
a) contacting said sample with a composition comprising:
i) a substrate with a surface comprising discrete sites; and ii) a population of microspheres comprising at least a first and a second subpopulation each comprising a bioactive agent;
wherein said microspheres are distributed on said surface such that said discrete sites contain microspheres; and b) determining the presence or absence of said target analyte by detecting said optical signature.
33. A method of determining the presence of a target analyte in a sample comprising:
a) contacting said sample with a composition comprising:
i) a substrate with a surface comprising discrete sites; and ii) a population of microspheres comprising at least a first and a second subpopulation each comprising:
1) a bioactive agent; and 2) an identifier binding ligand that will bind a decoder binding ligand comprising an optical signature comprising a nanocrystal such that the identification of the bioactive agent can be elucidated;
wherein said microspheres are distributed on said surface such that said discrete sites contain microspheres;
b) contacting said sample with a plurality of said decoder binding ligands;
and c) determining the presence or absence of said target analyte by detecting said optical signature.
34. A method according to claim 32 or 33 wherein the size of said nanocrystal contributes to said optical signature.
35. A method of decoding an array composition comprising a) providing an array composition comprising:
i) a substrate with a surface comprising discrete sites; and ii) a population of microspheres comprising at least a first and a second subpopulation, wherein each subpopulation comprises a bioactive agent;
wherein said microspheres are distributed on said surface;
b) adding a plurality of decoding binding ligands comprising optical signatures to said array composition to identify the location of at least a plurality of the bioactive agents, wherein at least one of said optical signatures comprises a nanocrystal.
36. A method according to claim 35 wherein at least two of said optical signatures comprise a nanocrystal, and wherein at least one of said optical signatures comprises a nanocrystal differing in size from a nanocrystal of another optical signature and wherein said size contributes to said optical signature.
37. A method according to claim 35 wherein at least one subpopulation of microspheres comprises an identifier binding ligand to which a decoding binding ligand can bind.
38. A method according to claim 35 wherein said decoding binding ligands bind to said bioactive agents.
39. A method according to claim 35 wherein the location of each subpopulation is determined by said optical signature.
40. A method of making a composition comprising:
a) adhering nanocrystals to porous silica beads; and b) sealing the pores of said silica beads using the sol-gel polymerization process.
CA2374735A 1999-05-20 2000-05-22 Encoding and decoding of array sensors utilizing nanocrystals Expired - Lifetime CA2374735C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/315,584 US6544732B1 (en) 1999-05-20 1999-05-20 Encoding and decoding of array sensors utilizing nanocrystals
US09/315,584 1999-05-20
PCT/US2000/013940 WO2000071995A2 (en) 1999-05-20 2000-05-22 Encoding and decoding of array sensors utilizing nanocrystals

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CA2374735A1 true CA2374735A1 (en) 2000-11-30
CA2374735C CA2374735C (en) 2010-04-13

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US (2) US6544732B1 (en)
EP (1) EP1181534B1 (en)
AT (1) ATE259060T1 (en)
AU (1) AU5442200A (en)
CA (1) CA2374735C (en)
DE (1) DE60008099T2 (en)
WO (1) WO2000071995A2 (en)

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