Implantable microelectronic biochemical sensor incorporating thin film thermopile

• US 4,935,345 A
• Filed: 12/30/1987
• Issued: 06/19/1990
• Est. Priority Date: 04/07/1987
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Guilbeau, Eric J., Towe, Bruce C.
• Primary Examiner(s): Nguyen, Nam X.
• Application Number:
  US07/142,297
• Time in Patent Office: 902 Days
• Field of Search: 435/288, 435/289, 435/290, 435/291, 435/817, 435/25, 435/27, 435/14, 435/4, 128/632, 128/635, 204/1 T, 204/403
• US Class Current: 435/14
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 25/4866 by using a differential method
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

A biochemical sensor is provided for measuring the concentration of a chemical dissolved within a fluid by providing a differential voltage proportional to a temperature differential resulting from the heat evolved from the enzymatic reaction of the chemical under test. The biochemical sensor is formed by depositing thin films of two dissimilar metals upon a substrate using microelectronic fabrication techniques. A multiplicity of thermocouple junctions are created at the intersections of the two dissimilar metal films, and the resulting series-connected thermocouple junctions are alternately designated sensing and reference junctions. The sensing junctions, but not the reference junctions, are covered by an enzyme, catalyst, or other species for initiating a chemical reaction involving the chemical under test, giving rise to a temperature differential between the sensing and reference junctions proportional to the concentration of the chemical under test. The biochemical sensor may be implanted within a human body for continuously monitoring concentrations of glucose or other chemicals present within the bloodstream.

Claims

1. A sensor for providing an electrical voltage representative of the concentration of a chemical dissolved in a fluid, said sensor comprising in combination:

a. a supporting substrate;

b. a thin film thermopile disposed upon said supporting substrate, said thin film thermopile including a plurality of pairs of thin film thermocouple junctions, each of said pairs of thermocouple junctions including a reference junction and a sensing junction electrically coupled in series connection with one another and spaced apart from one another, said reference junction and said sensing junction within each pair of thin film thermocouple junctions creating a temperature-dependent voltage when said reference junction and said sensing junction are electrically coupled in series connection, said plurality of pairs of thermocouple junctions being electrically coupled in series connection with one another between first and second terminals;

c. a layer of a substance disposed proximate to each of said sensing junctions, said substance facilitating chemical reactions involving said chemical dissolved in said fluid adjacent said sensing junctions but not adjacent said reference junctions; and

d. wiring means coupled to said first and second terminals of said plurality of pairs of thin film thermocouple junctions for providing a voltage difference signal proportional to a difference in temperature proximate the sensing and reference junctions arising from chemical reactions facilitated by said substance.

2. A sensor as recited by claim 1 wherein said plurality of pairs of thin film thermocouple junctions are formed by alternating, series-connected traces of first and second materials, respectively, said first material being different from said second material for creating a thermoelectric potential when brought together at a junction.

3. A sensor as recited by claim 2 wherein said first and second materials are each metals.

4. A sensor as recited by claim 3 wherein said first and second materials are Antimony and Bismuth, respectively.

5. A sensor as recited by claim 2 wherein said first and second materials are each semiconductors.

6. A sensor as recited by claim 2 wherein said first and second materials are each metal alloys.

7. A sensor as recited by claim 2 wherein said first and second materials are each alloys of the chemical element Tellurium.

8. A sensor as recited by claim 1 wherein said substance is a catalyst.

9. A sensor as recited by claim 8 wherein said catalyst is an enzyme.

10. A sensor as recited by claim 8 wherein said catalyst includes glucose oxidase for causing the chemical decomposition of glucose into gluconic acid and hydrogen peroxide.

11. A sensor as recited by claim 10 wherein said catalyst includes catalase for causing the chemical decomposition of hydrogen peroxide into water and oxygen gas.

12. A sensor as recited by claim 1 wherein said substance is a microorganism.

13. A sensor as recited by claim 1 wherein said substance is an organelle.

14. A sensor as recited by claim 1 wherein said sensing junctions are disposed upon said substrate as a grouping to facilitate the coverage by said substance of said grouping of sensing junctions, and wherein half of said reference junctions are disposed on one side of said grouping while the other half of said reference junctions are disposed on an opposite side of said grouping for the purpose of cancelling the effects of thermal eddies within said fluid.

15. A sensor as recited by claim 1 further including a layer of insulating material disposed over said plurality of pairs of thin-film thermocouple junctions to electrically insulate said plurality of pairs of said thin film thermocouple junctions from said fluid, said layer of said substance being disposed upon said layer of insulating material.

16. A sensor as recited by claim 1 wherein said supporting substrate includes a relatively thin portion having a first surface on one side thereof upon which said plurality of thin film thermocouple junctions are disposed, said relatively thin portion of said supporting substrate having a second surface on an opposite side thereof, said layer of said substance being disposed upon said second surface.

17. A sensor as recited in claim 16 further including means for forming a cavity about said first surface of said relatively thin portion of said supporting substrate to isolate said first surface from said fluid and to minimize the conduction of heat therefrom.

18. A sensor as recited in claim 1 wherein said supporting substrate consists of a semiconductor.

19. A method of measuring the concentration of a chemical within the bloodstream of a human body, said method comprising the steps of:

(a) implanting within the human body a sensor as described in claim 1, said layer of a substance facilitating chemical reactions involving said chemical within the bloodstream;

(b) measuring the voltage difference signal provided by said wiring means; and

(c) deriving from said voltage difference signal an indication of the concentration of said chemical within the bloodstream of the human body.

20. The method of claim 19 wherein the chemical for which the concentration is to be measured is glucose and wherein said layer of a substance facilitating chemical reactions is a glucose catalyst.

21. A sensor for providing an electrical voltage representative of the concentration of a chemical dissolved in a fluid, said sensor comprising in combination:

a. a supporting substrate;

b. a thin film thermopile disposed upon said supporting substrate, said thin film thermopile including a plurality of pairs of thin film thermocouple junctions disposed upon said supporting substrate, each of said pairs of thermocouple junctions including a reference junction and a sensing junction electrically coupled in series connection with one another and spaced apart form one another, said reference junction and said sensing junction within each pair of thin film thermocouple junctions creating a temperature-dependent voltage when said reference junction and said sensing junction are electrically coupled in series connection, said plurality of pairs of thermocouple junctions being electrically coupled in series connection with one another between first and second terminals;

c. a layer of a substance disposed proximate to each of said sensing junctions, said substance facilitating chemical reactions involving said chemical dissolved in said fluid adjacent said sensing junctions but not adjacent said reference junctions;

d. wiring means coupled to said first and second terminals of said plurality of pairs of thin film thermocouple junctions for providing a voltage difference signal proportional to a difference in temperatures proximate the sensing and reference junctions arising from chemical reactions facilitated by said substance; and

e. a catheter having a tip for insertion within a human body, said supporting substrate being secured within said tip of said catheter for being inserted within a human body to measure the concentration of a chemical within body fluid.

22. A sensor for providing an electrical voltage representative of the concentration of a chemical dissolved in a fluid, said sensor operating substantially independently of the absolute temperature of said fluid, said sensor comprising in combination:

a. a supporting substrate;

b. a thin film thermopile disposed upon said supporting substrate, said thin film thermopile including a plurality of pairs of thin film thermocouple junctions, each of said pairs of thermocouple junctions including a reference junction and a sensing junction electrically coupled in series connection with one another and spaced apart from one another, said reference junction and said sensing junction within each pair of thin film thermocouple junctions each creating a temperature-dependent voltage, each such pair of thermocouple junctions creating an electrical potential proportional in magnitude to the temperature difference between the reference junction and the sensing junction thereof, said plurality of pairs of thermocouple junctions being electrically coupled in series connection with one another between first and second terminals to multiply the electrical potential difference created by each such pair of thin film thermocouple junctions;

c. a layer of a substance disposed proximate to each of said sensing junctions but not overlying the reference junctions, said substance facilitating chemical reactions involving said chemical dissolved in said fluid adjacent said sensing junctions but not adjacent said reference junctions; and

d. wiring means coupled to said first and second terminals of said thin film thermopile for providing a voltage difference signal proportional to the difference between the temperature proximate the sensing junctions and the temperature proximate the reference junctions arising from chemical reactions facilitated by said substance adjacent said sensing junctions but not adjacent said reference junctions.

23. A method of measuring the concentration of a chemical within a fluid substantially independently of the absolute temperature of the fluid, the method comprising the steps of:

a. placing within the fluid a sensor, the sensor including a thin film thermopile disposed upon a supporting substrate and including a plurality of pairs of thin film thermocouple junctions, each of said pairs of thermocouple junctions including a reference junction and a sensing junction electrically coupled in series connection with one another and spaced apart from one another, said reference junction and said sensing junction within each pair of thin film thermocouple junctions each creating a temperature-dependent voltage, each such pair of thermocouple junctions creating an electrical potential proportional in magnitude to the temperature difference between the reference junction and the sensing junction thereof, said plurality of pairs of thermocouple junctions being electrically coupled in series connection with one another between first and second terminals to multiply the electrical potential difference created by each such pair of thin film thermocouple junctions, the sensor including a layer of a substance disposed proximate to each of said sensing junctions but not overlying the reference junctions, said substance facilitating chemical reactions involving said chemical dissolved in said fluid adjacent said sensing junctions but not adjacent said reference junctions;

b. measuring a voltage difference signal across the first and second terminals of the thin film thermopile to detect the difference between the temperature proximate the sensing junctions and the temperature proximate the reference junction arising from chemical reactions facilitated by said substance adjacent said sensing junction but not adjacent said reference junctions; and

c. deriving from said voltage difference signal an indication of the concentration of said chemical within the fluid.

24. A method of measuring the concentration of a chemical within the blood of a living body substantially independently of the absolute temperature of the blood, said method comprising the steps of:

a. contacting the blood of the living body with a sensor, the sensor including a thin film thermopile disposed upon a supporting substrate and including a plurality of pairs of thin film thermocouple junctions, each of said pairs of thermocouple junctions including a reference junction and a sensing junction electrically coupled in series connection with one another and spaced apart from one another, said reference junction and said sensing junction within each pair of thin film thermocouple junctions each creating a temperature-dependent voltage, each such pair of thermocouple junctions creating an electrical potential proportional in magnitude to the temperature difference between the reference junction and the sensing junction thereof, said plurality of pairs of thermocouple junctions being electrically coupled in series connection with one another between first and second terminals to multiply the electrical potential difference created by each such pair of thin film thermocouple junctions, the sensor including a layer of a substance disposed proximate to each of said sensing junctions but not overlying the reference junctions, said substance facilitating chemical reactions involving said chemical dissolved in said blood adjacent said sensing junctions but not adjacent said reference junctions;

b. measuring a voltage difference signal provided by said wiring means; and

c. deriving from said voltage difference signal an indication of the concentration of said chemical within the blood of the living body.