Sensor arrays for the measurement and identification of multiple analytes in solutions

• US 6,680,206 B1
• Filed: 07/16/1999
• Issued: 01/20/2004
• Est. Priority Date: 07/16/1998
• Status: Active Grant

• 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.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): HANDY, DWAYNE K
• Application Number:
  US09/354,882
• Time in Patent Office: 1,649 Days
• Field of Search: 422/52, 422/55, 422/57, 422/68.1, 422/58, 422/82.05, 422/82.06, 422/82.07, 422/82.08, 422/99, 422/100, 436/164, 436/165, 436/172, 436/174, 436/178, 436/180, 435/4, 435/7.1, 435/7.2, 435/287.1, 435/287.2, 435/287.3, 435/287.8
• US Class Current: 436/172
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 435/973 Simultaneous determination of more than one analyte
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/25 including sample preparation

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, and wherein the cavity is configured such that the fluid entering the cavity passes through the supporting member;

a particle, the particle positioned within the cavity, wherein the particle is configured to produce a signal when the particle interacts with the analyte during use, and wherein the cavity is configured to substantially inhibit movement of the particle within the support member; and

a cover positioned at a distance above the upper surface of the supporting member such that an opening is formed between the supporting member and the cover to allow the fluid to enter the cavity via the opening, and wherein the cover inhibits dislodgment of the particle from the cavity during use;

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 the system is configured to substantially simultaneously detect a plurality of analytes in the fluid.

3. The system of claim 1, wherein the system comprises a plurality of particles positioned within 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 red light emitting diode, a blue light emitting diode, and a green light emitting diode.

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

7. The system of claim 1, wherein the sensor array further comprises a bottom layer coupled to the supporting member, wherein the bottom layer is removable.

8. The system of claim 1, wherein the sensor array further comprises a bottom layer coupled to the supporting member, wherein the bottom layer is removable, and wherein the bottom layer includes openings that are substantially aligned with the cavities during use.

9. The system of claim 1, wherein the cavity is substantially tapered such that a 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.

10. The system of claim 1, 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.

11. The system of claim 1, wherein the cover layer is removable.

12. The system of claim 1, wherein the supporting member comprises a plastic material.

13. The system of claim 1, wherein the supporting member comprises a silicon wafer.

14. The system of claim 1, wherein the supporting member comprises a dry film photoresist material.

15. The system of claim 1, wherein the supporting member comprises a plurality of layers of a dry film photoresist material.

16. The system of claim 1, wherein an inner surface of the cavity is coated with a reflective material.

17. The system of claim 1, further comprising channels in the supporting member, wherein the channels are configured to allow the fluid to flow through the channels into and away from the cavity.

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

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

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

21. The system of claim 20, wherein the polymeric resin comprises polystyrene-polyethylene glycol-divinyl benzene.

22. The system of claim 20, wherein the receptor molecule produces the signal in response to the pH of the fluid.

23. The system of claim 20, wherein the analyte comprises a metal ion, and wherein the receptor produces the signal in response to the presence of the metal ion.

24. The system of claim 20, wherein the analyte comprises a carbohydrate, and wherein the receptor produces a signal in response to the presence of a carbohydrate.

25. The system of claim 20, wherein the particle further comprises a first indicator and a second indicator, the first and second indicators being coupled to the receptor, wherein an interaction of the receptor with the analyte causes the first and second indicators to interact such that the signal is produced.

26. The system of claim 20, 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.

27. The system of claim 20, wherein the receptor comprises a polynucleotide.

28. The system of claim 20, wherein the receptor comprises a peptide.

29. The system of claim 20, wherein the receptor comprises an enzyme.

30. The system of claim 20, wherein the receptor comprises a synthetic receptor.

31. The system of claim 20, wherein the receptor comprises an unnatural biopolymer.

32. The system of claim 20, wherein the receptor comprises an antibody.

33. The system of claim 20, wherein the receptor comprises an antigen.

34. The system of claim 1, wherein the analyte comprises phosphate functional groups, and wherein the particle is configured to produce the signal in the presence of the phosphate functional groups.

35. The system of claim 1, wherein the analyte comprises bacteria, and wherein the particle is configured to produce the signal in the presence of the bacteria.

36. 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.

37. A method of sensing an analyte in a fluid comprising:

passing a fluid over a sensor array system, the sensor array system comprising;

a light source;

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

at least one particle positioned within a cavity of a supporting member, wherein the cavity is configured to substantially inhibit movement of the particle within the support member;

a cover positioned at a distance above the upper surface of the supporting member such that an opening is formed between the supporting member and the cover to allow the fluid to enter the cavity via the opening, and wherein the cover inhibits dislodgment of the particle from the cavity during use;

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

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;

monitoring a spectroscopic change of the particle as the fluid is passed over the sensor array, wherein the spectroscopic change is caused by the interaction of the analyte with the particle.

38. The method of claim 37, wherein the spectroscopic change comprises a change in absorbance of the particle.

39. The method of claim 37, wherein the spectroscopic change comprises a change in fluorescence of the particle.

40. The method of claim 37, wherein the spectroscopic change comprises a change in phosphorescence of the particle.

41. The method of claim 37, wherein the particle comprises a receptor coupled to a polymeric resin, and further comprising exposing the particle to an indicator prior to passing the fluid over the sensor array.

42. The method of claim 41, wherein a binding strength of the indicator to the receptor is less than a binding strength of the analyte to the receptor.

43. The method of claim 42, wherein the indicator is a fluorescent indicator.

44. The method of claim 37, further comprising treating the fluid with an indicator prior to passing the fluid over the sensor array, wherein the indicator is configured to couple with the analyte.

45. The method of claim 37, wherein monitoring the spectroscopic change is performed with a CCD device.

46. The method of claim 37, further comprising measuring the intensity of the spectroscopic change, and further comprising calculating the concentration of the analyte based on the intensity of the spectroscopic change.

47. The method of claim 37, wherein monitoring the spectroscopic change comprises:

directing a red light source at the particle;

detecting the absorbance of red light by the particle;

directing a green light source at the particle;

detecting the absorbance of green light by the particle;

directing a blue light source at the particle; and

detecting the absorbance of blue light by the particle.