Small volume in vitro analyte sensor

• US 9,891,185 B2
• Filed: 05/16/2016
• Issued: 02/13/2018
• Est. Priority Date: 10/08/1998
• Status: Expired due to Fees

• 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): Kaur, Gurpreet
• Application Number:
  US15/155,681
• Publication Number:
  US 20160334356A1
• Time in Patent Office: 638 Days
• 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 sensor for determining concentration of an analyte in a sample fluid, the sensor comprising:

a first electrode disposed on a first substrate and a second electrode disposed on a second substrate, wherein the first electrode and the second electrode are in a facing configuration;

a spacer comprising a first part and a second part disposed between the first and second substrates, wherein the first part of the spacer, the second part of the spacer, the first substrate, and the second substrate define a first aperture along a first side edge of the sensor and a second aperture along a second side edge of the sensor, wherein either the first aperture or the second aperture is used for sample fluid application and the sensor has no more than two apertures;

a sample chamber for holding the sample fluid and sized to contain a volume of no more than about 1 μ

L of the sample fluid, wherein the sample chamber has a length which extends from the first aperture to the second aperture and a substantially uniform width between the first part of the spacer and the second part of the spacer along the entire length of the sample chamber, and wherein the width of the sample chamber is not wider than either the first aperture or the second aperture; and

an analyte-responsive enzyme and a redox mediator disposed in the sample chamber, wherein;

the first and second substrates define the sensor comprising a proximal end having a width and a distal end having a width, the distal end being configured for insertion into a sensor reader,

the width of the distal end is greater than the width of the proximal end, and

the distal end comprises a first extension and a second extension, wherein the first and second extensions are separated by a gap.

2. The sensor of claim 1, wherein the first electrode comprises palladium and the second electrode comprises gold.

3. The sensor of claim 1, wherein the first electrode and the second electrode are separated by an effective distance in a range of 25 to 1000 μ

m.

4. The sensor of claim 1, wherein the sensor comprises an indicator electrode disposed in the sensor to indicate when the sample chamber contains the sample fluid.

5. The sensor of claim 4, wherein the indicator electrode is also the first electrode or the second electrode.

6. The sensor of claim 4, comprising a visual or auditory sign, coupled to the indicator electrode, that activates when the indicator electrode indicates that the sample chamber contains the sample fluid.

7. The sensor of claim 1, wherein each of the first and second extensions comprises an electrical contact region for making electrical contact with a contact pad of the sensor reader.

8. The sensor of claim 1, wherein the redox mediator comprises ferricyanide.

9. The sensor of claim 1, wherein the analyte is glucose.

10. The sensor of claim 9, wherein the analyte-responsive enzyme is glucose dehydrogenase.

11. A method for determining a concentration of an analyte in a sample, comprising:

contacting the sample with an electrochemical sensor comprising;

a working electrode disposed on a first substrate and a second electrode disposed on a second substrate, wherein the working electrode and the second electrode are in a facing configuration;

a spacer comprising a first part and a second part disposed between the first and second substrates, wherein the first part of the spacer, the second part of the spacer, the first substrate, and the second substrate define a first aperture along a first side edge of the sensor and a second aperture along a second side edge of the sensor, wherein either the first aperture or the second aperture is used for sample application and the electrochemical sensor has no more than two apertures;

a sample chamber for holding the sample and sized to contain a volume of no more than about 1 μ

L of the sample, wherein the sample chamber has a length which extends from the first aperture to the second aperture and a substantially uniform width between the first part of the spacer and the second part of the spacer along the entire length of the sample chamber, and wherein the width of the sample chamber is not wider than either the first aperture or the second aperture; and

an analyte-responsive enzyme and a redox mediator disposed in the sample chamber, wherein;

the first and second substrates define the electrochemical sensor comprising a proximal end having a width and a distal end having a width, the distal end being configured for insertion into a sensor reader,

the width of the distal end is greater than the width of the proximal end, and

the distal end comprises a first extension and a second extension, wherein the first and second extensions are separated by a gap;

generating a sensor signal at the working electrode; and

determining the concentration of the analyte using the sensor signal.

12. The method according to claim 11, wherein determining the concentration of the analyte comprises determining the concentration of the analyte by amperometry using the sensor signal.

13. The method according to claim 11, comprising:

providing calibration data on a batch of the electrochemical sensors to a measurement instrument, said calibration data comprising information related to a magnitude of a background charge for the batch of the electrochemical sensors;

wherein the step of determining the concentration of the analyte comprises determining the concentration of the analyte using the sensor signal and the calibration data.

14. The method according to claim 11, comprising obtaining the sample from a subject.

15. The method according to claim 14, wherein the sample is blood obtained from a finger of the subject.

16. The method according to claim 14, wherein the sample is blood obtained from a region of the subject having a lower nerve end density as compared to a fingertip.

17. The method according to claim 16, wherein the region of the subject having a lower nerve end density as compared to a fingertip is selected from the group consisting of:

a forearm region, and a thigh region.

18. The method according to claim 11, wherein the first electrode comprises palladium and the second electrode comprises gold.

19. The method according to claim 11, wherein each of the first and second extensions comprises an electrical contact region for making electrical contact with a contact pad of the sensor reader.

20. The method according to claim 11, wherein the analyte is glucose.