Small volume in vitro analyte sensor and methods of making

• US 20040060818A1
• Filed: 09/12/2003
• Published: 04/01/2004
• Est. Priority Date: 10/08/1998
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Therasense Incorporated (Abbott Laboratories Incorporated)
• Inventors: Krishnan, Rajesh, Heller, Ephraim, Heller, Adam, Colman, Fredric C., Feldman, Benjamin J., Mao, Fei, Funderburk, Jeffery V., Vivolo, Joseph A.
• Granted Patent: US 7,225,535 B2
• Time in Patent Office: Days
• US Class Current: 204/403.01
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/32 involving dehydrogenase
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: Y10T 156/1052 with cutting, punching, tearing or severing
• CPC Class Codes: Y10T 29/49002 Electrical device making
• CPC Class Codes: Y10T 29/49004 including measuring or testing of device or component part
• CPC Class Codes: Y10T 29/49007 Indicating transducer
• CPC Class Codes: Y10T 29/49126 Assembling bases
• CPC Class Codes: Y10T 29/49128 Assembling formed circuit to base
• CPC Class Codes: Y10T 29/4913 Assembling to base an electrical component, e.g., capacitor, etc.
• CPC Class Codes: Y10T 29/49147 Assembling terminal to base
• CPC Class Codes: Y10T 29/49155 Manufacturing circuit on or in base
• CPC Class Codes: Y10T 29/49204 Contact or terminal manufacturing
• CPC Class Codes: Y10T 29/49208 by assembling plural parts
• CPC Class Codes: Y10T 29/4921 with bonding
• CPC Class Codes: Y10T 29/49794 Dividing on common outline

Abstract

A sensor utilizing a non-leachable or diffusible redox mediator is described. The sensor includes a sample chamber to hold a sample in electrolytic contact with a working electrode, and in at least some instances, the sensor also contains a non-leachable or a diffusible second electron transfer agent. The sensor and/or the methods used produce a sensor signal in response to the analyte that can be distinguished from a background signal caused by the mediator. The invention can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum, using techniques such as coulometry, amperometry, and potentiometry. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is typically provided as a second electron transfer agent.

Claims

1. A method of manufacturing electrochemical sensors, the method comprising steps of:

(a) forming a plurality of working electrodes on a first region of a substrate;

(b) forming a plurality of counter electrodes on a second region of the substrate;

(c) folding the substrate to overlay the first region and the second region;

(d) creating a sample chamber region between the first region and the second region; and

(e) separating a plurality of electrochemical sensors, each electrochemical sensor comprising at least one working electrode, at least one counter electrode, and at least one sample chamber region.

2. The method according to claim 1, wherein the step of folding the substrate comprises:

(a) scoring the substrate to form a score line; and

(b) folding the substrate along the score line.

3. The method according to claim 1, further comprising:

(a) positioning a spacer layer between the first region and the second region.

4. The method according to claim 3, wherein the step of positioning a spacer layer comprises:

(a) positioning an adhesive layer between the first region and the second region.

5. The method according to claim 4, further comprising:

(a) forming a plurality of indicator electrodes on the substrate in at least one of the first region and the second region; and

(b) wherein the step of separating a plurality of electrochemical sensors comprises;

(i) separating a plurality of electrochemical sensors, each electrochemical sensor comprising at least one working electrode, at least one counter electrode, at least one indicator electrode, and at least one sample chamber region.

6. The method according to claim 1, wherein:

(a) the step of forming a plurality of working electrodes on a first region of a substrate comprises;

(i) forming a plurality of working electrodes on a first region of a substrate having a width and a length, the plurality of working electrodes arranged in columns parallel to the width and in rows parallel to the length; and

(b) the step of forming a plurality of counter electrodes on a second region of the substrate comprises;

(i) forming a plurality of counter electrodes on a second region of the substrate, the plurality of counter electrodes arranged in columns parallel to the width and in rows parallel to the length.

7. A method of manufacturing electrochemical sensors, the method comprising steps of:

(a) forming a plurality of working electrodes on a first substrate;

(b) forming a plurality of counter electrodes on a second substrate;

(c) forming a plurality of indicator electrodes on one of the first substrate and the second substrate;

(d) overlaying the first substrate and the second substrate to form a layered structure;

(e) creating a sample chamber region between the first substrate and the second substrate; and

(f) separating a plurality of electrochemical sensors, each electrochemical sensor comprising at least one working electrode, at least one counter electrode, at least one indicator electrode, and at least one sample chamber region.

8. The method according to claim 7, wherein:

(a) the step of forming a plurality of working electrodes on a first substrate comprises;

(i) forming a plurality of working electrodes on a first region of the first substrate; and

(b) the step of forming a plurality of counter electrodes on a second substrate comprises;

(i) forming a plurality of counter electrodes on a second region of the first substrate.

9. The method according to claim 7, further comprising:

(a) forming a plurality of working electrode contact pads;

(b) forming a plurality of counter electrode contact pads;

(c) forming a plurality of indicator electrode contact pads; and

(d) wherein the step of separating a plurality of electrochemical sensors comprises;

(i) separating a plurality of electrochemical sensors, each electrochemical sensor having at least one working electrode contact pad, at least one counter electrode contact pad, and at least one indicator electrode contact pad.

10. The method according to claim 9, wherein the step of separating a plurality of electrochemical sensors further comprises:

(a) cutting the second substrate to expose the working electrode contact pads,

(b) cutting the first substrate to expose the counter electrode contact pads.

11. The method according to claim 10, wherein:

(a) the step of cutting the second substrate comprises;

(i) die cutting the second substrate; and

(b) the step of cutting the first substrate comprises;

(i) die cutting the first substrate.

12. The method according to claim 10, wherein after the steps of cutting:

(a) slitting the layered structure to provide individual electrochemical sensors.

13. The method according to claim 9, wherein:

(a) the step of forming a plurality of working electrode contact pads comprises;

(i) forming a plurality of working electrode contact pads, each working electrode contact pad in electrical contact with one of the working electrodes;

(b) the step of forming a plurality of counter electrode contact pads comprises;

(i) forming a plurality of counter electrode contact pads, each counter electrode contact pad in electrical contact with one of the counter electrodes; and

(c) the step of forming a plurality of indicator electrode contact pads comprises;

(i) forming a plurality of indicator electrode contact pads, each indicator electrode contact pad in electrical contact with one of the indicator electrodes.

14. The method according to claim 7, further comprising:

(a) depositing an enzyme over a portion of the working electrodes or the counter electrodes.

15. The method according to claim 14, further comprising:

(a) depositing an enzyme continuously over a portion of at least two of the working electrodes or at least two of the counter electrodes.

16. The method according to claim 7, further comprising:

(a) depositing a redox mediator over a portion of the working electrodes or the counter electrodes.

17. The method according to claim 16, further comprising:

(a) depositing a redox mediator continuously over a portion of at least two of the working electrodes or two of the counter electrodes.