Methods of making and using composite arrays for the detection of a plurality of target analytes

• US 7,510,841 B2
• Filed: 01/28/2004
• Issued: 03/31/2009
• Est. Priority Date: 12/28/1998
• Status: Expired due to Fees

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Stuelpnagel, John, Chee, Mark, Auger, Steven
• Primary Examiner(s): Horlick; Kenneth R.
• Assistant Examiner(s): Baughman; Molly E
• Application Number:
  US10/767,249
• Publication Number:
  US 20040185482A1
• Time in Patent Office: 1,889 Days
• Field of Search: 435/6, 435/7.1
• US Class Current: 435/7.1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00382 Stamping
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00524 in the shape of fiber bundles
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: G01N 33/54393 : Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding

Abstract

The invention relates to sensor compositions comprising a composite array of individual arrays, to allow for simultaneous processing of a number of samples. The invention further provides methods of making and using the composite arrays. The invention further provides a hybridization chamber for use with a composite array.

Claims

1. A method of detecting the presence or absence of a plurality of different target analytes, comprising

(a) providing a first substrate with a surface comprising a plurality of assay wells, wherein said assay wells contain sample solutions each having a plurality of different target analytes;

(b) providing a second substrate comprising a plurality of array locations, each array location comprising a plurality of discrete sites on a projection, wherein said sites comprise different bioactive agents;

(c) dipping the projections of said second substrate into said assay wells such that each array location of said second substrate contacts sample solution in a different well of said first substrate under conditions suitable for binding of said different target analytes to said different bioactive agents, thereby processing said sample solutions in parallel; and

(d) detecting the presence or absence of said target analytes.

2. The method of claim 1, wherein said target analytes comprise nucleic acids or nucleic acid analogs.

3. The method of claim 2, wherein said nucleic acids comprise single nucleotide polymorphisms.

4. The method of claim 3, wherein said nucleic acids comprise single nucleotide polymorphisms obtained by multiplex PCR amplification.

5. The method of claim 2, wherein said nucleic acids are labeled with fluorochromes during PCR amplification.

6. The method of claim 1, wherein said bioactive agents are selected from the group consisting of peptides, peptide structural analogs, saccharides, fatty acids, steroids, purines, and pyrimidines.

7. The method of claim 1, wherein said array locations comprise from 10,000,000 to 2,000,000,000 bioactive agents per square centimeter.

8. The method of claim 1, wherein said array locations comprise from 100,000 to about 10,000,000 bioactive agents per square centimeter.

9. The method of claim 1, wherein said array locations comprise from 10,000 to about 100,000 bioactive agents per square centimeter.

10. The method of claim 1, wherein said bioactive agents are directly coupled to said array locations.

11. The method of claim 1, wherein said bioactive agents are attached to microspheres and wherein said microspheres. are associated with said array locations.

12. The method of claim 1, wherein said target analytes comprise decoder binding ligands.

13. The method of claim 1, wherein said target analyte is labeled.

14. The method of claim 13, wherein said label comprises an optical label.

15. The method of claim 14, wherein said optical label comprises. a fluorochrome.

16. The method of claim 1, wherein said detecting is done through the use of a change in optical signature.

17. The method of claim 1, further comprising quantitating differences in concentrations of said target analytes.

18. The method of claim 17, further comprising quantitating a specific mRNA.

19. The method of claim 18, comprising quantitating said specific mRNA in the presence of total cellular mRNA.

20. The method of claim 1, wherein said assay wells comprise wells of a microtiter plate.

21. The method of claim 1, wherein said plurality of assay wells comprises 96 wells.

22. The method of claim 1, wherein said plurality of assay wells comprises 384 wells.

23. The method of claim 1, wherein said plurality of assay wells comprises 1536 wells.

24. The method of claim 1, wherein optical signals generated at said discrete sites upon binding of said different target analytes to said different bioactive agents are detected.

25. The method of claim 24, wherein said different target analytes comprise labels and wherein said optical signal occurs as a result of said labels recruited to said sites by said target analytes binding said different bioactive agents.

26. The method of claim 24, wherein an enzyme generates species at said discrete sites that are optically detectable.

27. The method of claim 1, further comprising using said projections to stir said sample solutions in said assay wells.