Encoding and decoding of array sensors utilizing nanocrystals

• US 6,544,732 B1
• Filed: 05/20/1999
• Issued: 04/08/2003
• Est. Priority Date: 05/20/1999
• Status: Expired due to Term

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Zhao, Chanfeng, Barnard, Steven M., Chee, Mark S.
• Primary Examiner(s): Chin, Christopher L.
• Assistant Examiner(s): DO, PENSEE T
• Application Number:
  US09/315,584
• Time in Patent Office: 1,419 Days
• Field of Search: 436/8, 436/2, 436/4, 436/5, 436/518, 436/523, 436/524, 436/164, 436/805, 436/823, 435/7.1, 435/174
• US Class Current: 435/6.11
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 33/587 Nanoparticles
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/823 Immunogenic carrier or carrier per se
• CPC Class Codes: Y10S 977/70 Nanostructure
• CPC Class Codes: Y10S 977/776 Ceramic powder or flake
• CPC Class Codes: Y10S 977/789 in array format
• CPC Class Codes: Y10S 977/792 Nucleic acid array, e.g. human genome array
• CPC Class Codes: Y10S 977/795 Composed of biological material
• CPC Class Codes: Y10S 977/898 Enzymatic
• CPC Class Codes: Y10S 977/902 Specified use of nanostructure
• CPC Class Codes: Y10S 977/904 for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10S 977/915 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

1. A composition comprising:

a) a substrate with a surface comprising discrete sites, wherein said discrete sites are wells; and

b) a population of microspheres randomly distributed on said discrete 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 1 wherein said nanocrystal is sealed into porous silica using a 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 1 wherein said microspheres comprise bioactive agents.

9. A composition according to claim 8 wherein said bioactive agents comprise nucleic acids.

10. A composition according to claim 8 wherein said bioactive agents comprise proteins.

11. A composition according to claim 10 wherein said proteins are selected from the group consisting of enzymes and antibodies.

12. A composition according to claim 1 wherein said population of microspheres comprises at least a first and a second subpopulation comprising:

i) 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.

13. A composition according to claim 12 wherein at least one of said optical signatures comprises at least two nanocrystals.

14. An array composition comprising:

a) a substrate with a surface comprising discrete sites, wherein said discrete sites are wells; 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 randomly distributed on said surface.

16. A composition according to claim 14 or 15 wherein said bioactive agents are nucleic acids.

17. A composition according to claim 14 or 15 wherein said bioactive agents are proteins.

15. An array composition comprising:

a) a substrate with a surface comprising discrete sites, wherein said discrete sites are wells; 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 randomly distributed on said surface.

18. An array composition comprising:

a) a substrate with a surface comprising discrete sites, wherein said discrete sites are wells; 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 randomly distributed on said surface.