Sensor arrays for detecting analytes in fluids

• US 5,959,191 A
• Filed: 01/13/1998
• Issued: 09/28/1999
• Est. Priority Date: 03/27/1995
• Status: Expired due to Term

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Lewis, Nathan S., Freund, Michael S.
• Primary Examiner(s): WIGGINS, JOHN DAVID
• Application Number:
  US09/006,279
• Time in Patent Office: 623 Days
• Field of Search: 73/31.05, 73/23.34, 73/23.3, 73/53.01, 73/61.43, 73/61.41, 73/23.33, 422/82.01, 422/83, 422/90, 422/68.1, 436/514, 436/151, 324/693
• US Class Current: 73/31.05
• CPC Class Codes: G01N 27/126 comprising organic polymers
• CPC Class Codes: G01N 33/0031 comprising two or more sensors, e.g. a sensor array electrochemical electrode arrays G01N27/27
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

Chemical sensors for detecting analytes in fluids comprise first and second conductive elements (e.g. electrical leads) electrically coupled to and separated by a chemically sensitive resistor which provides an electrical path between the conductive elements. The resistor comprises a plurality of alternating nonconductive regions (comprising a nonconductive organic polymer) and conductive regions (comprising a conductive material) transverse to the electrical path. The resistor provides a difference in resistance between the conductive elements when contacted with a fluid comprising a chemical analyte at a first concentration, than when contacted with a fluid comprising the chemical analyte at a second different concentration. Arrays of such sensors are constructed with at least two sensors having different chemically sensitive resistors providing dissimilar such differences in resistance. Variability in chemical sensitivity from sensor to sensor is provided by qualitatively or quantitatively varying the composition of the conductive and/or nonconductive regions. An electronic nose for detecting an analyte in a fluid may be constructed by using such arrays in conjunction with an electrical measuring device electrically connected to the conductive elements of each sensor.

Claims

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

a first chemically sensitive resistor comprising a first blend of a first nonconductive polymer and nonconductive polymer, and a conductive material arranged in a matrix of non-conductive and conductive regions;

a second chemically sensitive resistor comprising a second blend of a first nonconductive polymer and nonconductive polymer, and a conductive material arranged in a matrix of non-conductive and conductive regions;

a conductive material;

electrical measuring apparatus electrically connected to said first resistor and to said second resistor,

wherein during use, the permeation of the first blend of nonconductive polymers by the analyte in the first chemically sensitive resistor produces a first resistance which is different from a baseline resistance of the first resistor, the permeation of the second blend of nonconductive polymers by the analyte in the second chemically sensitive resistor produces a second resistance which is different from a baseline resistance of the second resistor, and wherein the difference between the first resistance and the baseline resistance of the first resistor is different from the difference between the second resistance and the baseline resistance of the second resistor.

2. The sensor of claim 1, wherein said first nonconductive polymer in said first chemically sensitive resistor is the same as said first nonconductive polymer in said second chemically sensitive resistor.

3. The sensor of claim 1, wherein said second nonconductive polymer in the first chemically sensitive resistor is the same as said second nonconductive polymer in the second chemically sensitive resistor.

4. The sensor of claim 1, wherein the first nonconductive polymer and the second nonconductive polymer are organic polymers.

5. The sensor of claim 1, wherein the conductive material is an organic conducting polymer.

6. The sensor of claim 1, wherein the conductive material is a carbonaceous material.

7. The sensor of claim 1, wherein the conductive material is a charge transfer complex.

8. The sensor of claim 1, wherein the conductive material is an inorganic conductor.

9. The sensor of claim 1, wherein the conductive material is a mixed inorganic organic conductor.

10. The sensor of claim 1, wherein the conductive material is a doped semiconductor.

11. The sensor of claim 1, wherein the conductive material is a conductive metal oxide.

12. The sensor of claim 1, wherein the conductive material is a superconductor.

13. The sensor of claim 1, further comprising an information storage device coupled to said electrical measuring apparatus.

14. The sensor of claim 1, wherein said electrical measuring apparatus includes an integrated circuit.

15. The sensor of claim 2, wherein concentration of the first nonconductive polymer in the first blend of the first chemically sensitive resistor is different from the concentration of the first nonconductive polymer in the second blend of the second chemically sensitive resistor.

16. The sensor of claim 4, wherein the first nonconductive polymer is selected from the group consisting of poly(styrene), poly(a-methyl styrene), poly(n-vinyl pyrrolidone), poly(4-vinyl phenol), poly(vinyl butral), poly(vinyl acetate), and poly(bis phenol A carbonate).

17. The sensor of claim 4, wherein the second nonconductive polymer is selected from the group consisting of poly(acrylonitrile), poly(maleic anhydride), and poly(allyl alcohol).

18. The sensor of claim 4, wherein the first nonconductive polymer and the second nonconductive polymer are selected from the group consisting of main-chain carbon polymers, main-chain acyclic heteroatom polymers and main-chain heterocyclic polymers.

19. The sensor of claim 18, wherein the main-chain carbon polymer is selected from the group consisting of polydienes, polyalkenes, polyacrylics, polymethacrylics, polyvinyl ethers, polyvinyl thioethers, polyvinyl alcohols, polyvinyl ketones, polyvinyl halides, polyvinyl nitriles, polyvinyl esters, polystyrenes and polyarylenes.

20. The sensor of claim 18, wherein the main-chain acyclic heteroatom polymer is selected from the group consisting of polyoxides, polycarbonates, polyesters, polyanhydrides, polyurethanes, polysulfonates, polysiloxanes, polysulfides, polythioesters, polysulfones, polysulfonamides, polyamides, polyureas, polyphosphazenes, polysilanes and polysilazanes.

21. The sensor of claim 18, wherein the main-chain heterocyclic polymer is selected from the group consisting of polyfuran tetracarboxylic acid diimides, polybenzoxazoles, polyoxadiazoles, polybenzothiazinophenothiazines, polybenzothiazoles, polypyrazinoquinoxalines, polypyromellitimides, polyquinoxalines, polybenzimidazoles, polyoxindoles, polyoxoisoindolines, polydioxoisoindolines, polytriazines, polypyridazines, polypiperazines, polypyridines, polypiperidines, polytriazoles, polypyrazoles, polypyrrolidines, polycarboranes, polyoxabicyclononanes, polydibenzofurans, polyphthalides, polyacetals, polyanhydrides and carbohydrates.

22. The sensor of claim 5, wherein the organic conducting polymer is selected from the group consisting of polyanilines, polythiophenes, polypyrroles, and polyacetylenes.

23. The sensor of claim 6, wherein the carbonaceous material is selected from the group consisting of carbon blacks, graphite, coke and C₆₀.

24. The sensor of claim 7, wherein the charge transfer complex is selected from the group consisting of tetramethylparaphenylenediamine-chloranile, alkali metal tetracyanoquinodimethane complexes and tetrathiofulvalene halide complexes.

25. The sensor of claim 8, wherein the inorganic conductor is selected from the group consisting of metals and metal alloys.

26. The sensor of claim 25, wherein the metal and metal alloys are selected from the group consisting of Ag, Au, Cu, Pt, and AuCu.

27. The sensor of claim 9, wherein the mixed inorganic organic conductor is selected from the group consisting of tetracyanoplatinate complexes, iridium halocarbonyl complexes, and stacked macrocyclic complexes.

28. The sensor of claim 10, wherein the doped semiconductor is selected from the group consisting of Si, GaAs, InP, MoS₂, and TiO₂.

29. The sensor of claim 11, wherein the conductive metal oxide is selected from the group consisting of In₂ O₃, SnO₂, and Na_x Pt₃ O₄.

30. The sensor of claim 12, wherein the superconductor is selected from the group consisting of YBa₂ Cu₃ O₇, Ti₂ Ba₂ Ca₂ Cu₃ O₁₀.

31. The sensor of claim 13, wherein said information storage device is a computer.

32. The method of claim 14, wherein said integrated circuit includes neural network-based hardware.

33. The method of claim 14, wherein said integrated circuit includes a digital-analog converter.

34. A method for detecting the presence of an analyte in a fluid, comprising the steps of:

providing a first chemically sensitive resistor having a baseline resistance, a first measured resistance response to permeation by said fluid and a first resistance response to permeation by said analyte, said first chemically sensitive resistor comprising a mixture of a nonconductive polymer and a conductive material;

providing a second chemically sensitive resistor having a baseline resistance, a second measured resistance response to permeation by said fluid and a second resistance response to permeation by said analyte, said second chemically sensitive resistor comprising a mixture of a nonconductive polymer and a conductive material;

providing an electrical measuring apparatus electrically connected to the first resistor and to the second resistor;

exposing the first resistor and the second resistor to the fluid;

measuring said first resistance response that occurs when the first resistor is permeated by the fluid, and said second resistance response that occurs when the second resistor is permeated by the fluid;

comparing the first measured resistance response to the first resistance response to permeation by the analyte to generate a first indicator which indicates the presence of the analyte in the fluid, and comparing the second measured resistance response to the second resistance response to permeation by the analyte to generate a second indicator which indicates the presence of the analyte in the fluid.

35. The method of claim 34, further comprising the step of comparing said first indicator and said second indicator to create a response pattern.

36. The method of claim 34, further comprising the steps of:

providing an information storage device coupled to said electrical measuring apparatus; and

storing information in said information storage device.

37. The method of claim 34, further comprising the steps of:

comparing the first measured resistance response to said stored first resistance response to permeation by the analyte to generate a first storage-referenced indicator which indicates the presence of the analyte in the fluid; and

comparing the second measured resistance response to said stored second resistance response to permeation by the analyte to generate a second storage-referenced indicator which indicates the presence of the analyte in the fluid.

38. The method of claim 34, wherein said electrical measuring apparatus includes an integrated circuit.

39. The method of claim 34, wherein the step of measuring the resistance response is performed using a multiplexing digital ohmmeter.

40. The method of claim 35, further comprising the step of using said response pattern to indicate the absence of a substance different from the analyte in the fluid.

41. The method of claim 35, wherein the information storage device is a computer.

42. The method of claim 35, wherein said stored information is the first resistance response to permeation by the analyte for said first resistor and the second resistance response to permeation by the analyte for said second resistor.

43. The method of claim 36, wherein said stored information is a database.

44. The method of claim 36, wherein said stored information is the resistance response of the resistor as a function of time.

45. The method of claim 37, further comprising the step of comparing said first storage-referenced indicator and said second storage-referenced indicator to create a storage-referenced response pattern that indicates the identity of the analyte in the fluid.

46. The method of claim 37, further comprising the step of comparing said first storage-referenced indicator and said second storage-referenced indicator to create a storage-referenced response pattern that indicates the concentration of the analyte in the fluid.

47. The method of claim 38, wherein said integrated circuit includes neural network-based hardware.

48. The method of claim 38, wherein said integrated circuit includes a digital-analog converter.

49. A method for detecting the presence of an analyte in a fluid, comprising the steps of:

providing a first chemically sensitive element having a first detectable measured response to permeation by said fluid and a first detectable response to permeation by said analyte, said first element comprising a first blend of first and second polymers and a conductive material arranged in a matrix of non-conductive and conductive regions;

providing a second chemically sensitive element having a second detectable measured response to permeation by said fluid and a second detectable response to permeation by said analyte, said second element comprising a second blend of first and second polymers and a conductive material arranged in a matrix of non-conductive and conductive regions;

providing a detector operatively associated with the first and second chemically sensitive elements;

exposing the chemically sensitive elements to said fluid;

measuring said first detectable measured response of the first element that occurs when the first element is permeated by the fluid, and said second detectable measured response of the second element that occurs when the second element is permeated by the fluid;

comparing the first detectable measured response of the first element to said first detectable response to permeation by the analyte for the first element to generate a first indicator which indicates the presence of the analyte in the fluid; and

comparing the second detectable measured response of the second element to said second detectable response to permeation by the analyte for the second element to generate a second indicator which indicates the presence of the analyte in the fluid.

50. The method of claim 49, wherein the first detectable response of the first chemically sensitive element to permeation by said analyte is a first detectable dynamic aggregate response to permeation by said analyte, and wherein the second detectable response of the second chemically sensitive element to permeation by said analyte is a second detectable dynamic aggregate response to permeation by said analyte,

wherein the step of comparing the first detectable measured response of the first element to said first detectable response to permeation by the analyte for the first element comprises comparing the first detectable measured response of the first element to said first detectable dynamic aggregate response to permeation by the analyte for the first element to generate a first indicator which indicates the presence of the analyte in the fluid, and

wherein the step of comparing the second detectable measured response of the second element to said second detectable response to permeation by the analyte for the second element comprises comparing the second detectable measured response of the second element to said second detectable dynamic aggregate response to permeation by the analyte for the second element to generate a second indicator which indicates the presence of the analyte in the fluid.

51. The method of claim 49, further comprising the step of comparing said first indicator and said second indicator to create a response pattern.

52. The method of claim 49, further comprising the steps of:

providing an information storage device coupled to said detector; and

storing information in said information storage device.

53. The method of claim 49, wherein said first polymer in the first chemically sensitive element is the same as said first polymer in the second chemically sensitive element, and said second polymer in the first chemically sensitive element is the same as said second polymer in said second chemically sensitive element.

54. The method of claim 49, wherein concentration of the first polymer in said first blend of the first chemically sensitive element is different from the concentration of the first polymer in said second blend of the second chemically sensitive element.

55. The method of claim 49, wherein, during use, the first detectable dynamic aggregate response of the first element is created as the space occupied by said first blend of polymers in the first element and the composition of the first blend change in a nonconstant fashion as the first blend is permeated by the analyte where such change in space and composition of the first blend is different from change in space and composition of the first polymer and is different from change in space and composition of the second polymer, and the second detectable dynamic aggregate response of the second element is created as the space occupied by said second blend of polymers in the second element and the composition of the second blend change in a nonconstant fashion as the second blend is permeated by the analyte where such change in space and composition of the second blend is different from change in space and composition of the first polymer and is different from change in space and composition of the second polymer.

56. The method of claim 49, wherein the first detectable measured response, the first detectable dynamic aggregate response, the second detectable measured response and the second detectable dynamic aggregate response are each variations in electrical resistance, and wherein the detector is an electrical measuring apparatus.

57. The method of claim 49, wherein the first chemically sensitive element does not further comprise a conductive material.

58. The method of claim 49, wherein the second chemically sensitive element does not further comprise a conductive material.

59. The method of claim 51, further comprising the step of using said response pattern to indicate the absence of a substance different from said analyte in the fluid.

60. The method of claim 52, wherein the information storage device is a computer.