Microfluidic microarray systems and methods thereof

• US 20060063160A1
• Filed: 09/22/2004
• Published: 03/23/2006
• Est. Priority Date: 09/22/2004
• Status: Active Grant

• Current Assignee: National Technology & Engineering Solutions Of Sandia LLC (Honeywell International Inc.)
• Original Assignee: Sandia National Laboratories (Government of the United States of America)
• Inventors: Hukari, Kyle W., Hux, Gary A., West, Jay A.A.
• Granted Patent: US 7,524,672 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1894 Cooling means; Cryo cooling
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/565 Seals in general F16L
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/629 being a microfluidic device
• CPC Class Codes: G01N 21/0303 : Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence

Abstract

Disclosed are systems that include a manifold in fluid communication with a microfluidic chip having a microarray, an illuminator, and a detector in optical communication with the microarray. Methods for using these systems for biological detection are also disclosed.

Claims

1. A system, comprising:

a manifold comprising a plurality of via holes in fluid communication with a plurality of microchannels disposed on a microfluidic chip, the microfluidic chip comprising a microarray, the microfluidic chip capable of transmitting light to the microarray, the microfluidic chip secured to the manifold;

an illuminator for providing the light; and

a detector in optical communication with the microarray.

2. The system of claim 1, wherein the microfluidic chip is secured to the manifold using a backing plate and a compression frame.

3. The system of claim 2, wherein the backing plate is optically transparent.

4. The system of claim 2, wherein the backing plate comprises diamond, quartz, glass, ceramic, silicon or plastic.

5. The system of claim 1, wherein the microfluidic chip is optically transparent.

6. The system of claim 1, wherein the manifold further comprises at least one port in fluid communication with at least one fluid source.

7. The system of claim 6, wherein the fluid source comprises buffer, solvent, sample, analyte, probe, label, tag, salts, acids, bases, detergents, or any combination thereof.

8. The system of claim 1, wherein the plurality of microchannels comprise open microchannels disposed on a surface of the microfluidic chip.

9. The system of claim 1, wherein the microarray is in fluid communication with at least one of the microchannels.

10. The system of claim 1, wherein the microarray comprises a plurality of biomolecules.

11. The system of claim 2, wherein the microfluidic chip is fluidically sealed to the backing plate.

12. The system of claim 1, wherein the microarray comprises at least about 100 biomolecular spots.

13. The system of claim 1, wherein the microarray comprises at least about 1000 biomolecular spots.

14. The system of claim 1, wherein the microarray comprises at least about 5000 biomolecular spots.

15. The system of claim 1, wherein the microarray comprises at least about 20,000 biomolecular spots.

16. The system of claim 1, wherein the microarray comprises at least about 50,000 biomolecular spots.

17. The system of claim 1, wherein at least a portion of the microfluidic chip is fluidically sealed to a substrate.

18. The system of claim 17, wherein the substrate comprises a film.

19. The system of claim 18, wherein the film is compressibly sealed to the microfluidic chip.

20. The system of claim 19, wherein the film comprises a semi-elastic plastic material.

21. The system of claim 1, wherein the microfluidic chip comprises a surface and features formed in the surface, whereby a film fluidically sealed to the features forms structures capable of containing or transporting a fluid.

22. The system of claim 18, wherein the film is fluidically sealed to the features using a compression plug.

23. The system of claim 22, wherein the compression plug is capable of maintaining pressure differentials of at least about 100 psi.

24. The system of claim 22, wherein the compression plug is capable of maintaining pressure differentials of at least about 200 psi.

25. The system of claim 22, wherein the compression plug is capable of maintaining pressure differentials of at least about 300 psi.

26. The system of claim 1, wherein the detector comprises a microscope, scanner, PMT, CCD, or any combination thereof.

27. The system of claim 26, wherein the detector comprises a CCD.

28. The system of claim 27, wherein the CCD is characterized as having a resolution of less than about 50 microns.

29. The system of claim 27, wherein the CCD is characterized as having a resolution of less than about 20 microns.

30. The system of claim 27, wherein the CCD is characterized as having a resolution of less than about 10 microns.

31. The system of claim 27, wherein the CCD is characterized as having a resolution of less than about 5 microns.

32. The system of claim 27, wherein the CCD is characterized as having a resolution of less than about 2 microns.

33. The system of claim 27, wherein the CCD is characterized as having a resolution of less than about 1 micron.

34. The system of claim 1, wherein the detector comprises at least about 10,000 pixels.

35. The system of claim 1, wherein the detector comprises up to about 100,000 pixels.

36. The system of claim 1, wherein the detector comprises at least about 1 million pixels.

37. The system of claim 1, wherein the detector comprises up to about 5 million pixels.

38. The system of claim 1, wherein the detector comprises up to about 10 million pixels.

39. The system of claim 1, wherein the detector is proximately located to the microarray.

40. The system of claim 1, wherein the microarray comprises a plurality of biomolecular spots disposed on the microarray.

41. The system of claim 1, further comprising an optical coupling situated between the microfluidic chip and the detector.

42. The system of claim 41, wherein the optical coupling comprises an optical waveguide, a lens, an optical fiber bundle, a glass or plastic rod, a fiber plate, an aperture, or any combination thereof.

43. The system of claim 42, wherein the optical coupling comprises a plurality of optical fibers, each of the fibers having a diameter in the range of from about 1 micron to about 10 microns.

44. The system of claim 43, wherein one end of each of the fibers is optically coupled to at least one pixel on the detector.

45. The system of claim 42, wherein the optical coupling provides a magnified image of the microarray to the detector.

46. The system of claim 1, wherein the detector comprises a plurality of pixels.

47. The system of claim 46, wherein at least a portion of the pixels are optically coupled to a plurality of biomolecular spots disposed on the microarray.

48. The system of claim 47, wherein each of the biomolecular spots is optically coupled to at least one pixel.

49. The system of claim 47, wherein each of the biomolecular spots is optically coupled, individually, to at least one pixel.

50. The system of claim 47, wherein each of the biomolecular spots is optically coupled to at least two pixels.

51. The system of claim 50, wherein each of the biomolecular spots is optically coupled to an individual group of at least two pixels.

52. The system of claim 47, wherein each of the pixels are, independently, optically coupled to one biomolecular spot.

53. The system of claim 47, wherein each pixel resolves, independently, one biomolecular spot.

54. The system of claim 40, wherein at least a portion of the biomolecular spots are capable of binding an analyte.

55. The system of claim 54, wherein each of the analyte comprises a fluorophore, a chromaphore, or any combination thereof.

56. The system of claim 55, wherein a photon emitted from the fluorophore or chromaphore is detected by the detector.

57. The system of claim 56, wherein a photon emitted from the fluorophore or chromaphore is optically communicated to a pixel on the detector.

58. The system of claim 47, wherein each of the biomolecular spots has a size in the range of from about 60 microns to about 200 microns.

59. The system of claim 47, wherein each of the biomolecular spots is located about 10 microns to about 100 microns from the at least one pixel.

60. The system of claim 1, wherein the illuminator is secured to the microfluidic chip.

61. The system of claim 60, wherein the illuminator is secured to an edge of the microfluidic chip.

62. The system of claim 1, wherein the illuminator comprises a waveguide.

63. The system of claim 62, wherein the waveguide comprises a fiber bundle.

64. The system of claim 1, wherein the illuminator comprises an LED, an incandescent light source, a fluorescent light source, an electroluminescent light source, a plasma light source, a laser, or any combination thereof.

65. The system of claim 1, wherein the illuminator comprises at least one LED coupled to at least one waveguide.

66. The system of claim 1, further comprising at least two illuminators capable of emitting the same or different wavelength of light.

67. The system of claim 66, wherein each of the illuminators are individually coupled to a waveguide.

68. The system of claim 67, wherein each of the illuminators emit a different wavelength of light.

69. The system of claim 68, where each of the illuminators comprise an LED.

70. The system of claim 1, further comprising a temperature controller.

71. The system of claim 70, wherein the temperature controller comprises a thermoelectric cooler.

72. The system of claim 70, wherein the temperature controller thermally contacts the microfluidic chip.

73. The system of claim 72, wherein the temperature controller is capable of heating and cooling the microfluidic chip.

74. The system of claim 73, wherein the temperature controller is capable of controlling the temperature of the microfluidic chip in the range of from about 4°

C. to about 120°

C.

75. The system of claim 1, wherein the manifold and the microfluidic chip are fluidically sealed with an O-ring at each via hole.

76. A method, comprising:

providing a system, comprising;

a manifold comprising a plurality of via holes in fluid communication with a plurality of microchannels disposed on a microfluidic chip, the microfluidic chip comprising a microarray, the microfluidic chip capable of transmitting light to the microarray, the microfluidic chip secured to the manifold;

an illuminator for providing the light; and

a detector in optical communication with the microarray;

binding at least one biomolecule to the microarray;

transmitting light through the microfluidic chip to the microarray; and

detecting the at least one bound biomolecule using the detector.

77. The method of claim 76, wherein the binding comprises hybridization of nucleic acids, interactions between two or more proteins, interactions between at least one nucleic acid and at least one protein, or any combination thereof.

78. The method of claim 76, wherein the biomolecule comprises a label, a tag, a dye, a biomarker, or any combination thereof, bound to the biomolecule.

79. A method, comprising:

fluidically connecting a microfluidic chip to a manifold comprising a plurality of via holes, the via holes being in fluid communication with the microfluidic chip, the microfluidic chip comprising an open channel microarray;

sealing the open channel microarray;

flowing biomolecules through at least a portion of the via holes to the microfluidic chip;

binding the biomolecules to the microarray;

transmitting light through the microfluidic chip to the microarray; and

detecting bound biomolecules.

80. The method of claim 79, wherein the biomolecules flow under the influence of a pressure differential, an electric potential, or both.

81. The method of claim 79, wherein the binding comprises hybridization of nucleic acids, interactions between two or more proteins, interactions between at least one nucleic acid and at least one protein, or any combination thereof.

82. The method of claim 79, wherein the biomolecule comprises a label, a tag, a dye, a biomarker, or any combination thereof, bound to the biomolecule.

83. The method of claim 79 further comprising controlling the temperature of the microfluidic chip, the manifold comprising, the microarray, the biomolecules, or any combination thereof.

84. The method of claim 83 wherein the microarray is cyclically heated and cooled.