Method and apparatus for the delivery of samples to a chemical sensor array

• US 7,022,517 B1
• Filed: 07/14/2000
• Issued: 04/04/2006
• Est. Priority Date: 07/16/1999
• Status: Expired due to Fees

• Current Assignee: University of Texas System
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Neikirk, Dean P., Anslyn, Eric V., McDevitt, John T., Shear, Jason B., Borich, Damon V.
• Primary Examiner(s): Le, Long V.
• Assistant Examiner(s): YANG, NELSON C
• Application Number:
  US09/616,731
• Time in Patent Office: 2,090 Days
• Field of Search: 422/68.1, 422 81- 8209, 4352865- 71, 4352884- 7, 435/808, 436/518, 436/524, 436/531, 436/56, 436/164, 436/172, 436/805
• US Class Current: 435/288.5
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/056 Laminated construction
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• 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 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6454 using an integrated detector array
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

A system for the rapid characterization of multi-analyte fluids, in one embodiment, includes a light source, a sensor array, and a detector. The sensor array is formed from a supporting member into which a plurality of cavities may be formed. A series of chemically sensitive particles are, in one embodiment positioned within the cavities. The particles may be configured to produce a signal when a receptor coupled to the particle interacts with the analyte. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized.

Claims

1. A system for detecting an analyte in a fluid comprising:

a light source;

a sensor array, the sensor array comprising a supporting member comprising at least one cavity formed within the supporting member;

a particle, the particle positioned in the cavity, wherein the particle produces a signal when the particle interacts with an analyte during use;

a vacuum apparatus at least partially incorporated into the supporting member, wherein the vacuum apparatus is coupled to the cavity, and wherein the vacuum apparatus produces a vacuum in the cavity such that the produced vacuum pulls fluid through the cavity during use, and wherein the vacuum apparatus comprises a vacuum chamber, and wherein the vacuum chamber comprises a breakable barrier positioned between the chamber and the cavity, and wherein the chamber applies a vacuum to the cavity when the breakable barrier is punctured; and

a detector, the detector being configured to detect the signal produced by the interaction of the analyte with the particle during use;

wherein the light source and detector are positioned such that light passes from the light source, to the particle, and onto the detector during use.

2. The system of claim 1, wherein the system comprises a plurality of particles positioned within a plurality of cavities, and wherein at least a first part of the plurality of particles is adapted to detect at least one analyte, and wherein the analyte that is detected by the portion of the plurality of particles is not detected by second part of the plurality of particles.

3. The system of claim 1, wherein the system comprises a plurality of particles positioned in the cavity.

4. The system of claim 1, wherein the light source comprises a light emitting diode.

5. The system of claim 1, wherein the light source comprises a white light source.

6. The system of claim 1, wherein the sensor array further comprises a bottom layer and a top cover layer, wherein the bottom layer is positioned below a bottom surface of the supporting member, and wherein the top cover layer is positioned above the upper surface of the supporting member, and wherein the bottom layer and the top cover layer are positioned such that the particle is substantially contained within the cavity by the bottom layer and the top cover layer.

7. The system of claim 1, wherein the bottom layer and the top cover layer are substantially transparent to light produced by the light source.

8. The system of claim 1, wherein the sensor array further comprises a bottom layer and a top cover layer, wherein the bottom layer is coupled to a bottom surface of the supporting member, and wherein the top cover layer is coupled to a top surface of the supporting member;

and wherein both the bottom layer and the top cover layer are coupled to the supporting member such that the particle is substantially contained within the cavity by bottom layer and the top cover layer.

9. The system of claim 8, wherein the bottom layer and the top cover layer are substantially transparent to light produced by the light source.

10. The system of claim 1, wherein the sensor array further comprises a bottom layer coupled to the supporting member, and wherein the supporting member comprises silicon, and wherein the bottom layer comprises silicon nitride.

11. The system of claim 1, further comprising a conduit coupled to the sensor array, wherein the conduit is configured to conduct the fluid sample to and away from the sensor array.

12. The system of claim 1, wherein the supporting member is formed from a plastic material, and wherein the sensor array further comprises a top cover layer, the top cover layer being coupled to the supporting member such that the particle is substantially contained within the cavity, and wherein the top cover layer comprises one or more openings that allow the fluid to pass through the top cover layer to the particle, and wherein both the supporting member and the top cover layer are substantially transparent to light produced by the light source.

13. The system of claim 1, wherein the cavities are configured to allow the fluid to pass through the supporting member during use.

14. The system of claim 13, wherein the cavity is configured to substantially contain the particle.

15. The system of claim 13, further comprising a cover layer coupled to the supporting member and a bottom layer coupled to the supporting member, wherein the cover layer and the bottom layer are removable.

16. The system of claim 13, further comprising a cover layer coupled to the supporting member and a bottom layer coupled to the supporting member, wherein the cover layer and the bottom layer are removable, and wherein the cover layer and the bottom layer include openings that are substantially aligned with the cavities during use.

17. The system of claim 13, further comprising a cover layer coupled to the supporting member and a bottom layer coupled to the supporting member, wherein the bottom layer is coupled to a bottom surface of the supporting member and wherein the cover layer is removable, and wherein the cover layer and the bottom layer include openings that are substantially aligned with the cavities during use.

18. The system of claim 13, further comprising a cover layer coupled to the supporting member and a bottom layer coupled to the supporting member, wherein an opening is formed in the cover layer substantially aligned with the cavity, and wherein an opening is formed in the bottom layer substantially aligned with the cavity.

19. The system of claim 13, wherein the cavity is substantially tapered such that the width of the cavity narrows in a direction from a top surface of the supporting member toward a bottom surface of the supporting member, and wherein a minimum width of the cavity is substantially less than a width of the particle.

20. The system of claim 13, wherein a width of a bottom portion of the cavity is substantially less than a width of a top portion of the cavity, and wherein the width of the bottom portion of the cavity is substantially less than a width of the particle.

21. The system of claim 13, further comprising a cover layer coupled to the supporting member and a bottom layer coupled to the supporting member, wherein the particle is positioned on the bottom layer, and wherein an opening is formed in the cover layer substantially aligned with the cavity.

22. The system of claim 13, wherein the supporting member comprises a dry film photoresist material.

23. The system of claim 13, wherein the supporting member comprises a plurality of layers of a dry film photoresist material.

24. The system of claim 13, wherein an inner surface of the cavity is coated with a reflective material.

25. The system of claim 1, wherein the detector comprises a charge-coupled device.

26. The system of claim 1, wherein the detector comprises an ultraviolet detector.

27. The system of claim 1, wherein the detector comprises a fluorescence detector.

28. The system of claim 1, wherein the detector comprises a semiconductor based photodetector, and wherein the detector is coupled to the sensor array.

29. The system of claim 1, wherein the particle ranges from about 0.05 micron to about 500 microns.

30. The system of claim 1, wherein a volume of the particle changes when contacted with the fluid.

31. The system of claim 1, wherein the vacuum apparatus comprises a vacuum pump.

32. The system of claim 1, wherein the particle comprises a receptor molecule coupled to a polymeric resin.

33. The system of claim 1, wherein the polymeric resin comprises polystyrene-polyethylene glycol-divinyl benzene.

34. The system of claim 33, wherein the receptor molecule produces the signal in response to the pH of the fluid.

35. The system of claim 33, wherein the analyte comprises a metal ion, and wherein the receptor produces the signal in response to the presence of the metal ion.

36. The system of claim 33, wherein the analyte comprises a carbohydrate, and wherein the receptor produces a signal in response to the presence of a carbohydrate.

37. The system of claim 33, wherein the particle further comprises a first indicator and a second indicator, the first and second indicators being coupled to the receptor, wherein the interaction of the receptor with the analyte causes the first and second indicators to interact such that the signal is produced.

38. The system of claim 33, wherein the particle further comprises an indicator, wherein the indicator is associated with the receptor such that in the presence of the analyte the indicator is displaced from the receptor to produce the signal.

39. The system of claim 33, wherein the receptor comprises a polynucleotide.

40. The system of claim 33, wherein the receptor comprises a peptide.

41. The system of claim 33, wherein the receptor comprises an enzyme.

42. The system of claim 33, wherein the receptor comprises a synthetic receptor.

43. The system of claim 33, wherein the receptor comprises an unnatural biopolymer.

44. The system of claim 33, wherein the receptor comprises an antibody.

45. The system of claim 33, wherein the receptor comprises an antigen.

46. The system of claim 33, wherein the analyte comprises phosphate functional groups, and wherein the particle produces the signal in the presence of the phosphate functional groups.

47. The system of claim 1, wherein the analyte comprises bacteria, and wherein the particle produces the signal in the presence of the bacteria.

48. The system of claim 1, wherein the system comprises a plurality of particles positioned within a plurality of cavities, and wherein the plurality of particles produce a detectable pattern in the presence of the analyte.

49. The system of claim 1, further comprising a filter coupled to the conduit and the sensor array, wherein the fluid passes through the filter before reaching the sensor array.

50. The system of claim 49, wherein the fluid is a blood sample, and wherein the filter comprises a membrane for the removal of particulates.

51. The system of claim 49, wherein the fluid is a blood sample, and wherein the filter comprises a membrane for removal of white and red blood cells from the blood.

52. The system of claim 1 further comprising a reagent delivery reservoir coupled to the sensor array via a conduit, wherein the fluid passes through the reagent delivery reservoir before entering the cavity, and wherein reagents enter the fluid as the fluid passes through the reagent delivery reservoir during use.

53. The system of claim 52, wherein the reagent delivery reservoir comprises an indicator.

54. A system for detecting an analyte in a fluid comprising:

a sensor array, the sensor array comprising a supporting member comprising at least one cavity formed within the supporting member;

a particle, the particle positioned within the cavity, wherein the particle produces a signal when the particle interacts with an analyte during use;

a vacuum apparatus at least partially incorporated into the supporting member, wherein the vacuum apparatus is coupled to the cavity, and wherein the vacuum apparatus produces a vacuum in the cavity such that the produced vacuum pulls fluid through the cavity during use, and wherein the vacuum apparatus comprises a vacuum chamber, and wherein the vacuum chamber comprises a breakable barrier positioned between the chamber and the cavity, and wherein the chamber applies a vacuum to the cavity when the breakable barrier is punctured; and

a detector, the detector being configured to detect the signal produced by the interaction of the analyte with the particle during use.

55. The system of claim 54, wherein the system comprises a plurality of particles positioned in a plurality of cavities, and wherein at least a first part of the plurality of particles is adapted to detect at least one analyte, and wherein the analyte that is detected by the portion of the plurality of particles is not detected by second part of the plurality of particles.

56. The system of claim 54, wherein the system comprises a plurality of particles positioned in the cavity.