Optimized capacitive sensor for chemical analysis and measurement

• US 4,822,566 A
• Filed: 05/18/1987
• Issued: 04/18/1989
• Est. Priority Date: 11/19/1985
• Status: Expired due to Term

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Newman, Arnold L.
• Primary Examiner(s): Marcus, Michael S.
• Application Number:
  US07/050,367
• Time in Patent Office: 701 Days
• Field of Search: 422/68, 422/90, 422/69, 422/83, 422/98, 204/403, 324/61 R, 324/61 C, 324/60 R, 324/71.1, 324/71.4, 436/DIG. 805, 436/DIG. 806, 436/525, 436/528, 425/288, 425/291, 425/817
• US Class Current: 422/82.01
• 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
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property

Abstract

An apparatus for detecting the presence and/or measuring the concentration of an analyte in the fluid medium is disclosed. The apparatus relies on biospecific binding between a biochemical binding system and the analyte to change the dielectric properties of a capacitive affinity sensor. The biological affinity sensor is optimized by: (1) adjusting the thickness and dielectric properties of a passivation layer to generally match the impedance of the biological binding system; and (2) minimize the double layer capacitance so that bulk capacitance changes associated with the biological binding system are maximized.

Claims

1. A device for detecting the presence of an analyte in a fluid having an aqueous solvent, said device comprising:

a sensing capacitor including;

a substrate having a first conductor and a second conductor spaced a distance from said first conductor,

an electrically insulating layer covering said first and second conductors, said electrically insulating layer defining a surface,

a binding agent selected from the group consisting of antigens, haptens, bioreceptors and antibodies capable of biospecifically binding with the analyte,

a linking molecule adapted for and covalently bonding said binding agent to said surface and extending said binding agent a distance from said surface to minimize steric hindrance between the analyte and the surface; and

,

a circuit means, electrically coupled to said sensing capacitor, responsive to changes in capacitance between said first and second conductors.

2. The device of claim 1, wherein said linking molecule extends said binding agent out beyond the electrical double layer.

7. The device of claim 1, wherein said first conductor comprises a plurality of fingers disposed on said substrate and wherein said second conductor comprises a plurality of fingers disposed on said substrate, fingers of said first conductor are interdigitated with fingers of said second conductor.

3. A device for detecting the present of an analyte in a fluid having an aqueous solvent, said device comprising:

a sensing capacitor including;

a substrate having a first conductor and a second conductor spaced a distance from said first conductor,

a binding agent selected from the group consisting of antigens, adapters, bioreceptors and antibodies capable of biospecifically binding with the analyte,

an electrically insulating layer covering said first and second conductors, said electrically insulating layer defining a surface, wherein the composition and thickness of said insulating layer is selected to produce a series capacitance smaller than the double layer series capacitance and approaching the series capacitance produced by the binding agent,

a linking molecule adapted for and covalently bonding said binding agent to said surface; and

,

a circuit means, electrically coupled to said sensing capacitor, responsive to changes in capacitance between said first and second conductors.

4. The device of claim 3, wherein the thickness and composition of said insulating layer is selected to produce a series capacitance less than 1 μ

f/cm².

5. The device of claim 3, wherein said insulating layer comprises an inner thin film of high dielectric ion impervious material and an outer layer of a material selected to provide binding compatbility with said linking molecules.

6. The device of claim 5, wherein said inner thin film is composed of silicon nitride and said outer layer is composed of silica (SiO₂).

8. The device for detecting the presence of an analyte in a liquid, said device comprising:

a sensing capacitor including,

a substrate having a first conductor and a second conductor spaced a distance from said first conductor,

an electrically insulating layer covering said first and second conductors, said electrically insulating layer defining a surface,

a first organic compound having a biospecific binding site,

a linking molecule adapted for and covalently bonding said first organic compound to said surface, and extending said first organic compound a distance from said surface to minimize steric hinderance between the analyte and the surface,

a binding agent composed essentially of an organic compound selected from the group consisting of antibodies, lectins, enzymes, and neural receptors and being reversibly bound to said first organic compound, said binding agent biospecifically reactive with both said first organic compound and said analyte, wherein exposure of said binding agent to a liquid containing analyte causes formation of a binding agent/analyte complex through competitive binding, said binding agent/analyte complex being free to diffuse from said surface; and

,

a circuit means, electrically coupled to said sensing capacitor, responsive to changes in capacitance between said first and second conductors.

9. The device of claim 8, wherein said linking molecule extends said first organic component out beyond the electrical double layer.

14. The device of claim 8, wherein said first conductor comprises a plurality of fingers disposed on said substrate and wherein said second conductor comprises a plurality of fingers disposed on said substrate, fingers of said first conductor are interdigitated with fingers of said second conductor.

15. The device of claim 8, further comprising a membrane encompassing said first and second conductors, said membrane having a pore size selected to pass analyte but not to pass said binding agent, so that said binding agent is retained in a volume adjacent to said first and said conductor encompassed by said membrane.

16. The device of claim 8, further comprising:

a reference capacitor comprising a substrate having a first conductor spaced apart from a second conductor, an electrically insulating layer covering such first and second conductor, said electrically insulating layer defining a reference surface; and

,

a reference circuit, electrically coupled to a said reference capacitor, responsive to changes in capacitance between said first and second conductors.

10. A device for detecting the presence of an analyte in a liquid, said device comprising:

a sensing capacitor including,

a substate having a first conductor and a second conductor spaced a distance from said first conductor,

an electrically insulating layer covering said first and second conductors, said electrically insulating layer defining a surface, wherein the composition and thickness of said insulating layer is selected to produce a series capacitance smaller than the double layer series capacitance,

a first organic compound having a biospecific binding site,

a linking molecule adapted for and covalently bonding said first organic compound to said surface,

a binding agent composed essentially of an organic compound selected from the group consisting of antibodies, lectins, enzymes, and neural receptors and neural receptors and being reversibly bound to said first organic compound, said binding agent biospecifically reactive with both said first organic compound and said analyte, wherein exposure of said binding agent to a liquid containing analyte causes formation of a binding agent/analyte complex through competitive binding, said binding agent/analyte complex being free to diffuse from said surface; and

,

a circuit means, electrically coupled to said sensing capacitor, responsive to changes in capacitance between said first and second conductors.

11. The device of claim 10, wherein the thickness and composition of said insulating layer is selected to produce a series capacitance less than 1 μ

f/cm².

12. The device of claim 10, wherein said insulating layer comprises an inner thin film of high dielectric ion impervious material and an outer layer of a material selected to provide binding compatibility with said linking molecules.

13. The device of claim 12, wherein said inner thin film is composed of silicon nitride and said outer layer is composed of silica (SiO₂).