Use of microfluidic systems in the detection of target analytes using microsphere arrays

• US 8,481,268 B2
• Filed: 11/17/2011
• Issued: 07/09/2013
• Est. Priority Date: 05/21/1999
• Status: Expired due to Fees

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Chee, Mark S., Dickinson, Todd A., Gunderson, Kevin, O'Neil, Don, Stuelpnagel, John R.
• Primary Examiner(s): Chunduru, Prabha
• Application Number:
  US13/299,235
• Publication Number:
  US 20120129716A1
• Time in Patent Office: 600 Days
• Field of Search: None
• US Class Current: 435/6.12
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2563/149 Particles, e.g. beads
• CPC Class Codes: C12Q 2565/629 being a microfluidic device

Abstract

The invention relates generally to methods and apparatus for conducting analyses, particularly microfluidic devices for the detection of target analytes.

Claims

1. A fluidics device comprising:

a first channel in fluid communication with an inlet;

a detection module in fluid communication with said first channel, said detection module comprising an array of wells in communication with a tantalum-containing substrate, a population of microspheres comprising at least a first and a second subpopulation, wherein each subpopulation comprises a bioactive agent and wherein said microspheres are distributed in said wells such that not more than one microsphere is present in each of the wells; and

a second channel in fluid communication with said detection module and an outlet.

2. The fluidics device of claim 1, wherein the bioactive agent comprises a nucleic acid.

3. The fluidics device of claim 2, wherein the nucleic acid comprises a primer.

4. The fluidics device of claim 3, further comprising an enzyme for extension of the primer.

5. The fluidics device of claim 1, wherein the first subpopulation and the second subpopulation of microspheres are different sized microspheres.

6. The fluidics device of claim 1, wherein the tantalum-containing substrate comprises a plurality of flow channels.

7. The fluidics device of claim 6, wherein at least two flow channels are parallel to each other.

8. The fluidics device of claim 1, wherein the tantalum-containing substrate is configured to hold multiple samples.

9. The fluidics device of claim 1, wherein the wells are randomly distributed on the tantalum-containing substrate.

10. The fluidics device of claim 1, wherein the wells are patterned on the tantalum-containing substrate.

11. The fluidics device of claim 1, further comprising a module in fluid communication with said first channel or with said second channel, said module selected from the group consisting of a sample inlet port, sample collection module, cell handling module, separation module, reaction module, fluid pump, fluid valve, heating module;

storage module, and mixing chamber.

12. The fluidics device of claim 11, wherein the fluid pump is selected from the group consisting of electroosmotic pump, and electrohydrodynamic pump.

13. The fluidic device of claim 1, wherein the substrate is a chargeable substrate.

14. A fluidics device comprising:

an inlet in fluid communication a first channel;

a detection module in fluid communication with said first channel and comprising;

an array of wells in communication with a tantalum-containing substrate, wherein the wells are configured to hold a single microsphere;

a population of microspheres comprising at least a first and a second subpopulation, wherein each subpopulation comprises a bioactive agent; and

a second channel in fluid communication with said detection module and an outlet.

15. The fluidics device of claim 14, wherein the bioactive agent comprises a nucleic acid.

16. The fluidics device of claim 15, wherein the nucleic acid comprises a primer.

17. The fluidics device of claim 16, further comprising an enzyme for extension of the primer.

18. The fluidics device of claim 14, wherein the first subpopulation and the second subpopulation of microspheres are different sized microspheres.

19. The fluidics device of claim 14, wherein the tantalum-containing substrate comprises a plurality of flow channels.

20. The fluidics device of claim 19, wherein at least two flow channels are parallel to each other.

21. The fluidics device of claim 14, wherein the tantalum-containing substrate is configured to hold multiple samples.

22. The fluidics device of claim 14, wherein the wells are randomly distributed on the tantalum-containing substrate.

23. The fluidics device of claim 14, wherein the wells are patterned on the tantalum-containing substrate.

24. The fluidics device of claim 14, further comprising a module in fluid communication with said first channel or with said second channel, said module selected from the group consisting of a sample inlet port, sample collection module, cell handling module, separation module, reaction module, fluid pump, fluid valve, heating module;

storage module, and mixing chamber.

25. The fluidics device of claim 24, wherein the fluid pump is selected from the group consisting of electroosmotic pump, and electrohydrodynamic pump.

26. The fluidic device of claim 14, wherein the substrate is a chargeable substrate.

27. A method of sequencing a nucleic acid comprising:

providing a fluid comprising a target nucleic acid to the inlet of the fluidics device of claim 17; and

sequencing said target nucleic acid.

28. The method of claim 27, wherein said sequencing comprises detecting an optical signal.

29. The method of claim 27, wherein said sequencing comprises detecting a non-optical signal.

30. A method of detecting an analyte comprising:

providing a fluid comprising a target analyte to the inlet of the fluidics device of claim 14; and

detecting the target analyte bound to at least one of said bioactive agents.

31. The method of claim 30, wherein said target analyte comprises a nucleic acid.

32. The method of claim 30, wherein said detecting comprises detecting an optical signal.

33. The method of claim 30, wherein said detecting comprises detecting a non-optical signal.

34. The fluidics device of claim 27, wherein the first subpopulation and the second subpopulation of microspheres are different sized microspheres.

35. The fluidics device of claim 27, wherein the tantalum-containing substrate comprises a plurality of flow channels.

36. The fluidics device of claim 35, wherein at least two flow channels are parallel to each other.

37. The fluidics device of claim 27, wherein the tantalum-containing substrate is configured to hold multiple samples.

38. The fluidics device of claim 27, wherein the wells are randomly distributed on the tantalum-containing substrate.

39. The fluidics device of claim 27, wherein the wells are patterned on the tantalum-containing substrate.

40. The fluidics device of claim 30, wherein the bioactive agent comprises a nucleic acid.

41. The fluidics device of claim 40, wherein the nucleic acid comprises a primer.

42. The fluidics device of claim 41, further comprising an enzyme for extension of the primer.

43. The fluidics device of claim 30, wherein the first subpopulation and the second subpopulation of microspheres are different sized microspheres.

44. The fluidics device of claim 30, wherein the tantalum-containing substrate comprises a plurality of flow channels.

45. The fluidics device of claim 44, wherein at least two flow channels are parallel to each other.

46. The fluidics device of claim 30, wherein the tantalum-containing substrate is configured to hold multiple samples.

47. The fluidics device of claim 30, wherein the wells are randomly distributed on the tantalum-containing substrate.

48. The fluidics device of claim 30, wherein the wells are patterned on the tantalum-containing substrate.