Methods of making small volume in vitro analyte sensors

• US 8,091,220 B2
• Filed: 10/31/2007
• Issued: 01/10/2012
• Est. Priority Date: 10/08/1998
• Status: Expired due to Term

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Feldman, Benjamin J., Heller, Adam, Heller, Ephraim, Mao, Fei, Vivolo, Joseph A., Funderburk, Jeffery V., Colman, Fredric C., Krishnan, Rajesh
• Primary Examiner(s): Nguyen, Donghai D.
• Application Number:
  US11/932,528
• Publication Number:
  US 20090014328A1
• Time in Patent Office: 1,532 Days
• Field of Search: 204/403.01, 204/403.03, 204/403.04, 204/409, 204/416, 205/777.5, 427/2.13, 435/287.5, 435/287.8, 435/287.9, 600/345, 600/347, 294/15, 29593-595, 298/30, 298/31, 298/74, 298/76, 298/77, 298/84
• US Class Current: 29/831
• 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:

forming a plurality of working electrodes on a first electrode region of a substrate;

forming a plurality of counter electrodes on a second electrode region of the substrate;

forming a plurality of indicator electrodes on one of the first and second electrode regions;

disposing a spacer layer on one of the first and second electrode regions;

removing a portion of the spacer layer to define sample chamber regions;

folding the substrate with the spacer layer between the first electrode region and the second electrode region to form a layered structure; and

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, at least one sample chamber region, and first and second lateral extensions from the sensor body flanking the sample chamber region to indicate to a user where the openings for the sample chamber are provided.

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

forming a plurality of working electrode contact pads;

forming a plurality of counter electrode contact pads; and

forming a plurality of indicator electrode contact pads;

wherein the step of separating a plurality of electrochemical sensors comprises 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.

3. The method according to claim 2, wherein the step of separating a plurality of electrochemical sensors further comprises cutting the second electrode region of the substrate to expose the working electrode contact pads and cutting the first electrode region of the substrate to expose the counter electrode contact pads.

4. The method according to claim 3, wherein the step of cutting the second electrode region of the substrate comprises die cutting the second electrode region, and wherein the step of cutting the first electrode region of the substrate comprises die cutting the first electrode region.

5. The method according to claim 3, wherein after the steps of cutting the layered structure is slit to provide individual electrochemical sensors.

6. The method according to claim 2, wherein:

the step of forming a plurality of working electrode contact pads comprises forming a plurality of working electrode contact pads, each working electrode contact pad in electrical contact with one of the working electrodes;

the step of forming a plurality of counter electrode contact pads comprises forming a plurality of counter electrode contact pads, each counter electrode contact pad in electrical contact with one of the counter electrodes; and

the step of forming a plurality of indicator electrode contact pads comprises forming a plurality of indicator electrode contact pads, each indicator electrode contact pad in electrical contact with one of the indicator electrodes.

7. The method according to claim 1, further comprising depositing an enzyme over a portion of the working electrodes or the counter electrodes.

8. The method according to claim 7, further comprising depositing an enzyme continuously over a portion of at least two of the working electrodes or at least two of the counter electrodes.

9. The method of claim 7, wherein the enzyme is glucose oxidase or glucose dehydrogenase.

10. The method according to claim 1, further comprising depositing a redox mediator over a portion of the working electrodes or the counter electrodes.

11. The method according to claim 10, further comprising depositing a redox mediator continuously over a portion of at least two of the working electrodes or two of the counter electrodes.

12. The method according to claim 1, wherein creating a sample chamber region comprises creating a sample chamber region having a volume of no more than 1 microliter.

13. The method according to claim 1, wherein creating a sample chamber region comprises creating a sample chamber region having a volume of no more than 0.5 microliter.

14. The method according to claim 1, wherein creating a sample chamber region comprises creating a sample chamber region having a volume of no more than 0.2 microliter.

15. The method according to claim 1, wherein creating a sample chamber region comprises creating a sample chamber region having a volume of no more than 0.1 microliter.

16. The method according to claim 1, wherein the folding step results in a space between the working and counter electrodes of no more than 200 microns.

17. The method according to claim 1, wherein the folding step results in a space between the working and counter electrodes of no more than 100 microns.

18. The method according to claim 1, wherein the folding step results in a space between the working and counter electrodes of no more than 50 microns.