Sensors with variable response behavior

• US 7,008,524 B2
• Filed: 08/29/2002
• Issued: 03/07/2006
• Est. Priority Date: 10/03/2000
• Status: Expired due to Fees

• Current Assignee: HRL Laboratories LLC (The Boeing Co.)
• Original Assignee: HRL Laboratories LLC (The Boeing Co.)
• Inventors: Stanford, Thomas B., Van Ast, Camille I., Yamagishi, Frederick G.
• Primary Examiner(s): Olsen, Kaj K.
• Application Number:
  US10/230,947
• Publication Number:
  US 20030062263A1
• Time in Patent Office: 1,286 Days
• Field of Search: 422/82.02, 422/83, 422/98, 204/403.01, 205/777.5, 205/792, 435/4, 435/5, 435/7.1, 435/7.9, 435/14, 435/25, 435/26, 435/28
• US Class Current: 205/777.5
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: G01N 27/3276 being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A sensor and method for detecting biological and chemical agents comprising metal interdigitized electrodes coated with hybrid polymer-based conducting film and an instrument for applying electrical voltage to the electrodes and registering the change in electrical current. The hybrid film also comprises indicator biomolecules encapsulated within the film or attached to it. The bioindicator molecules preferably comprise enzyme acetylcholinesterase. When these indicator biomolecules come in a contact with a pathogen, chemical and/or morphological changes occur in the film and electrical current flowing through the electrodes is modulated. The pathogen comprise inhibitors of enzymes, preferably organophosphates, thiophosphates or phosphonates. The change in current indicates the presence of a biological and chemical agent and is registered.

Claims

1. A sensor for detecting a chemical or biological molecule or a pathogen, said sensor comprising:

a dielectric substrate;

a plurality of interdigitated electrodes attached to said substrate;

a film applied over said plurality of interdigitated electrodes;

a film applied over said plurality of interdigitated electrodes, wherein said film comprises a conductive polymer and a first and a second sol-gel derived material;

one or more bioindicator molecules incorporated within said film, wherein said bioindicator molecule is ensconced within an interpenetrating network, wherein said network is formed by said first sol-gel derived material and said second sol-gel derived material; and

an instrument to measure an electric current flowing through said plurality of interdigitated electrodes.

2. The sensor of claim 1, wherein said dielectric substrate is fabricated of a material selected from the group consisting of quartz, glass, ceramic, and plastic.

3. The sensor of claim 1, wherein each of said plurality of interdigitated electrodes has a generally rectangular shape in a cross-section.

4. The sensor of claim 1, wherein each of said plurality of interdigitated electrodes has a width within a range of between about 5 micrometers and about 25 micrometers.

5. The sensor of claim 4, wherein said width is about 15 micrometers.

6. The sensor of claim 1, wherein said plurality of interdigitated electrodes includes at least one pair of electrodes defining a gap, wherein the gap is within a range of between about 5 micrometers and about 25 micrometers.

7. The sensor of claim 6, wherein said gap is about 15 micrometers.

8. The sensor of claim 1, wherein said bioindicator molecule is selected from the group consisting of enzymes, antibodies, and antibiotics.

9. The sensor of claim 8, wherein said enzymes are selected from the group consisting of acetylcholinesterase, glucose oxidase, α

-amylase, glutamate dehydrogenase, and organophosphorous hydrolase.

10. The sensor of claim 8, wherein said antibodies are selected from the group consisting of escherichia coli serotype 157:

H7 IgG, goat anti-human IgG(γ

), goat anti-bacillus anthracis antisera and anti-TNT IgG.

11. The sensor of claim 8, wherein said antibiotics are selected from the group consisting of penicillin, naficillin, and oxacillin.

12. The sensor of claim 1, wherein said instrument to measure said electric current is comprised of a voltage source and an ammeter.

13. The sensor of claim 1, wherein said plurality of interdigitated electrodes are fabricated of gold.

14. The sensor of claim 1, wherein said chemical or biological molecule is selected from the group consisting of inhibitors of enzymes, antigens of antibodies, and reactants of antibiotics.

15. The sensor of claim 14, wherein said inhibitors are selected from the group consisting of organophosphates, organothiophosphates, organophosphonates, and mixtures thereof.

16. The sensor of claim 1, wherein said plurality of interdigitated electrodes are attached to said substrate by an adhesion layer.

17. The sensor of claim 16, wherein said adhesion layer comprises a material selected from the group consisting of titanium and an alloy of titanium and tungsten.

18. The sensor of claim 1, wherein said conductive polymer is selected from the group consisting of polyaniline, polythiophene, polypyrrole, and derivatives thereof.

19. The sensor of claim 1, wherein said indicator biomolecule is ensconced within said first sol-gel derived material.

20. The sensor of claim 1, wherein said first and second sol-gel derived materials each comprise a product of gelation of two or more organosilicon compounds.

21. The sensor of claim 20, wherein said organosilicon compounds are selected from the group consisting of monofunctional silanes, difunctional silanes, trifunctional silanes, tetrafunctional silanes, derivatized silanes, and mixtures thereof.

22. The sensor of claim 21, wherein said monofunctional silanes are selected from the group consisting of octadecyldimethylmethoxysilane, other monofunctional silanes, and mixtures thereof;

wherein the other monofunctional silanes are hydrolyzable to form silanols that can dehydrate to form sol-gels.

23. The sensor of claim 21, wherein said difunctional silanes are selected from the group consisting of methyldimethoxysilane, dimethyldiethoxysilane, other difunctional silanes, and mixtures thereof;

wherein the other difunctional silanes are hydrolyzable to form silanols that can dehydrate to form sol-gels.

24. The sensor of claim 21, wherein said trifunctional and tetrafunctional silanes are selected from the group consisting of methyltrimethoxysilane, octadecyltrichlorosilane, octadecyltriethoxysilane, tetramethoxysilane, phenyltrimethoxysilane, 1,4-bis(trimethoxysilylethyl)benzene, other trifunctional and tetrafunctional silanes, and mixtures thereof;

wherein the other trifunctional and tetrafunctional silanes are hydrolyzable to form silanols that can dehydrate to form sol-gels.

25. The sensor of claim 21, wherein said derivatized silanes are selected from the group consisting of 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3 glycidoxypropyltrimethoxysilane, 4-aminobutyldimethylmethoxysilane, N-(2 aminoethyl)-3-aminopropylmethyldimethoxysilane, 5 (bicycloheptenyl)triethoxysilane, dicyclohexyldimethoxysilane, 3 glycidylpropyltrimethoxysilane, other derivatized silanes, and mixtures thereof;

wherein the other derivatized silanes are hydrolyzable to form silanols which can dehydrate to form sol-gels.

26. A method for detecting a chemical or biological molecule or a pathogen, the method comprising:

(a) exposing the sensor claimed in claim 1 to the chemical or biological molecule or pathogen;

(b) applying an electric voltage to the plurality of interdigitated electrodes of the sensor;

(c) measuring a change in an electric current flowing through the plurality of interdigitated electrodes.

27. The sensor of claim 1, wherein said bioindicator molecule is deoxyhemoglobin.

54. The sensor as claimed in claim 1, wherein the conductive polymer comprises polyaniline, polythiophene, and/or polypyrrole;

wherein the polyaniline, the polythiophene, and the polypyrrole are each optionally doped with one or more counterions; and

wherein the polyaniline, the polythiophene, and the polypyrrole each optionally include a ring having a methoxy substituent, an ethoxy substituent, a trifluoromethyl substituent, and/or an amino substituent.

55. The sensor as claimed in claim 54, wherein the counterions are selected from the group consisting of chloride, bisulfate, sulfonic acid, and dodecylbenzene sulfonic acid.

56. The sensor as claimed in claim 1, wherein the first sol-gel derived material forms a first sol-gel layer, wherein the second sol-gel derived material forms a second sol-gel layer on top of and in contact with the first sol-gel layer, and wherein the bioindicator molecule is sandwiched between the first sol-gel layer and the second sol-gel layer.

57. The sensor as claimed in claim 1, wherein the first sol-gel derived material forms a first sol-gel layer, wherein the second sol-gel derived material forms a second sol-gel layer on top of and in contact with the first sol-gel layer, and wherein the bioindicator molecule is ensconced or encapsulated within either the first sol-gel layer or the second-sol gel layer.

58. The sensor as claimed in claim 57, wherein the first sol-gel layer is in electrical contact with the interdigitated electrodes, and wherein the polymer is incorporated into the first sol-gel layer.

59. The sensor as claimed in claim 57, wherein the second sol gel layer is in electrical contact with the interdigitated electrodes, and wherein the polymer is incorporated into the second sol-gel layer.

28. A method for detecting a chemical or biological molecule or a pathogen, the method comprising the steps of:

disposing a plurality of interdigitated electrodes on a dielectric substrate;

applying a film over said plurality of interdigitated electrodes, wherein said film comprises a conductive polymer and a first and second sol-gel derived material;

incorporating one or more bioindicator molecules into said film by embedding said bioindicator molecule within said film or attaching said bioindicator molecule to said film, wherein said bioindicator molecule is ensconced within an interpenetrating network, wherein said network is formed by said first sol-gel derived material and said second sol-gel derived material;

exposing said film to an environment containing said chemical or biological molecule or pathogen;

applying an electric voltage to said plurality of interdigitated electrodes; and

measuring a change in an electric current flowing through said plurality of interdigitated electrodes, said change being caused by interaction of said chemical or biological molecule or pathogen with said film.

29. The method of claim 28, wherein said dielectric substrate is fabricated of a material selected from the group consisting of quartz, glass, ceramic, and plastic.

30. The method of claim 28, wherein each of said plurality of interdigitated electrodes is attached to said substrate with use of an adhesion layer.

31. The method of claim 30, wherein said adhesion layer comprises a material selected from the group consisting of titanium and an alloy of titanium and tungsten.

32. The method of claim 28, wherein each of said plurality of interdigitated electrodes has a generally rectangular shape in a cross-section.

33. The method of claim 28, wherein each of said plurality of interdigitated electrodes has a width within a range of between about 5 micrometers and about 25 micrometers.

34. The method of claim 33, wherein said width is about 15 micrometers.

35. The method of claim 28, wherein said plurality of interdigitated electrodes includes at least one pair of electrodes defining a gap, wherein the gap is within a range of between about 5 micrometers and about 25 micrometers.

36. The method of claim 35, wherein said gap is about 15 micrometers.

37. The method of claim 28, wherein said bioindicator molecule is selected from the group consisting of enzymes, antibodies, and antibiotics.

38. The method of claim 37, wherein said enzymes further comprise acetylcholinesterase.

39. The method of claim 37, wherein said enzymes are selected from the group consisting of glucose oxidase, α

-amylase, glutamate dehydrogenase, and organophosphorous hydrolase.

40. The method of claim 37, wherein said antibodies are selected from the group consisting of escherichia coli serotype 157:

H7 IgG, goat anti-human IgG(γ

), goat anti-bacillus anthracis antisera and anti-TNT IgG.

41. The method of claim 28, wherein an amount of said voltage is between about 5 millivolts and about 300 millivolts.

42. The method of claim 41, wherein said amount of said voltage is between about 10 millivolts and about 50 millivolts.

43. The method of claim 28, wherein said plurality of interdigitated electrodes are fabricated of an electrically conductive material comprising gold.

44. The method of claim 28, wherein said chemical or biological molecule is selected from the group consisting of inhibitors of enzymes, antigens of antibodies, and reactants of antibodies.

45. The method of claim 44, wherein said antibiotics are selected from the group consisting of penicillin, naficillin, and oxacillin.

46. The method of claim 44, wherein said inhibitors are selected from the group consisting of organophosphates, organothiophosphates, organophosphonates, and mixtures thereof.

47. The method of claim 28, wherein said bioindicator molecule is ensconced within said first sol-gel derived material.

48. The method of claim 28, wherein said first and second sol-gel derived materials each comprise a product of gelation of two or more organosilicon compounds.

49. The method of claim 48, wherein said organosilicon compounds are selected from the group consisting of monofunctional silanes, difunctional silanes, trifunctional silanes, tetrafunctional silanes, derivatized silanes, and mixtures thereof.

50. The method of claim 49, wherein said monofunctional silanes are selected from the group consisting of octadecyldimethylmethoxysilane, other monofunctional silanes, and mixtures thereof;

wherein the other monofunctional silanes are hydrolyzable to form silanols that can dehydrate to form sol-gels.

51. The method of claim 49, wherein said difunctional silanes are selected from the group consisting of methyldimethoxysilane, dimethyldiethoxysilane, other difunctional silanes, and a mixture thereof;

wherein the other difunctional silanes are hydrolyzable to form silanols that can dehydrate to form sol-gels.

52. The method of claim 49, wherein said trifunctional and tetrafunctional silanes are selected from the group consisting of methyltrimethoxysilane, octadecyltrichlorosilane, octadecyltriethoxysilane, tetramethoxysilane, phenyltrimethoxysilane, 1,4-bis(trimethoxysilylethyl)benzene, other trifunctional and tetrafunctional silanes, and mixtures thereof;

wherein the other trifunctional and tetrafunctional silanes are hydrolyzable to form silanols that can dehydrate to form sol-gels.

53. The method of claim 49, wherein said derivatized silanes are selected from the group consisting of 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-glycidoxypropyltrimethoxysilane, 4-aminobutyldimethylmethoxysilane, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, 5-(bicycloheptenyl)triethoxysilane, dicyclohexyldimethoxysilane, 3-glycidylpropyltrimethoxysilane, other derivatized silanes, and mixtures thereof wherein the other derivatized silanes are hydrolyzable to form silanols which can dehydrate to form sol-gels.

60. The method as claimed in claim 28, wherein the first sol-gel derived material forms a first sol-gel layer, wherein the second sol-gel derived material forms a second sol-gel layer on top of and in contact with the first sol-gel layer, and wherein the bioindicator molecule is sandwiched between the first sol-gel layer and the second sol-gel layer.

61. The method as claimed in claim 28, wherein the first sol-gel derived material forms a first sol-gel layer, wherein the second sol-gel derived material forms a second sol-gel layer on top of and in contact with the first sol-gel layer, and wherein the bioindicator molecule is ensconced or encapsulated within either the first sol-gel layer or the second-sol gel layer.

62. The method as claimed in claim 61, wherein the first sol-gel layer is in electrical contact with the interdigitated electrodes, and wherein the polymer is incorporated into the first sol-gel layer.

63. The method as claimed in claim 61, wherein the second sol-gel layer is in electrical contact with the interdigitated electrodes, and wherein the polymer is incorporated into the second sol-gel layer.

64. The method as claimed in claim 28, wherein the chemical or biological molecule or pathogen is in a fluid.

65. The method as claimed in claim 28, wherein the chemical or biological molecule or pathogen is in a gas or a liquid.

66. The method as claimed in claim 28, wherein the chemical or biological molecule or pathogen is in air or an aqueous environment.

67. The method of claim 28, wherein said bioindicator molecule is deoxyhemoglobin.