Analyte sensors employing multiple enzymes and methods associated therewith

Patent metadata

Field	Value
Publication number	US-12150761-B2
Application number	US-202217819099-A
Country	US
Kind code	B2
Filing date	Aug 11, 2022
Priority date	Jan 28, 2019
Publication date	Nov 26, 2024
Grant date	Nov 26, 2024

Abstract

Methods and analyte sensors including at least a first working electrode having a first active area thereon, and performing a dip coating operation to deposit a bilayer membrane upon the first working electrode and the first active area. The bilayer may include an inner layer having a first membrane polymer and an outer layer having a second membrane polymer, the first membrane polymer and the second membrane polymer differing from one another. The dip coating operation may comprise one or more first dips in a first membrane formulation to form the inner layer of the bilayer membrane and one or more second dips in a second membrane formulation to form the outer layer of the bilayer membrane upon the inner layer.

First claim

What is claimed is:

1. An analyte sensor comprising:
a first working electrode and a second working electrode, a first active area being present on the first working electrode, and a second active area being present on the second working electrode; and
a membrane comprising an inner layer comprising a first membrane polymer and an outer layer comprising a second membrane polymer;
wherein the first active area comprises a ketone-responsive enzyme,
wherein the second active area comprises an enzyme responsive to an analyte other than ketones,
wherein the sensor produces a signal from the first active area and a signal from the second active area that is independent of a signal from the first active area,
wherein the signal from the first active area and the signal from the second active area increase linearly as functions of analyte concentrations,
wherein the inner layer is disposed upon the first working electrode and the first active area, and the outer layer is disposed upon the inner layer and upon the second working electrode and the second active area, and
wherein the first membrane polymer comprises a crosslinked polyvinylpyridine homopolymer or copolymer,
wherein the sensor is configured to be partially inserted into a tissue.

2. The analyte sensor of claim 1 , wherein the first membrane polymer and the second membrane polymer differ from one another.

3. The analyte sensor of claim 1 , wherein the signal from the first active area increases linearly as a function of a first analyte concentration from 0 mM to 10 mM.

4. The analyte sensor of claim 1 , wherein the signal from the first active area increases linearly as a function of a first analyte concentration from 0 mM to 5 mM.

5. The analyte sensor of claim 1 , wherein the signal from the second active area increases linearly as a function of a second analyte concentration from 0 mM to 30 mM.

6. The analyte sensor of claim 1 , wherein the signals that increase linearly each have a sensitivity of about 1 nA/mM.

7. The analyte sensor of claim 1 , wherein the signals that increase linearly each have an R 2 value of at least 0.96.

8. The analyte sensor of claim 1 , wherein the signals that increase linearly each have an R 2 value of at least 0.99.

9. The analyte sensor of claim 1 , wherein the signal from the first active area has a mean signal loss of no more than 3.1% when exposed to a given ketone concentration for 2 weeks.

10. The analyte sensor of claim 1 , wherein the second active area includes a glucose-responsive enzyme.

11. The analyte sensor of claim 1 , wherein each signal varies a few tenths of a nA or less from an initial signal over 190 hours at a given analyte concentration.

12. The analyte sensor of claim 1 , wherein the signal from the first active area has a mean signal loss of no more than 3.1% when exposed to 8 mM of β-hydroxybutyrate in 100 mM phosphate buffered saline (PBS) at 33° C. for 2 weeks.

13. An analyte sensor comprising:
a first working electrode and a second working electrode, a first active area being present on the first working electrode and a second active area being present on the second working electrode; and
a membrane comprising an inner layer comprising a first membrane polymer and an outer layer comprising a second membrane polymer;
wherein the first active area comprises a ketone-responsive enzyme,
wherein the second active area comprises an enzyme responsive to an analyte other than ketones,
wherein the sensor produces a signal from the first active area and a signal from the second active area that is independent of a signal from the first active area,
wherein the signal from the first active area has a mean signal loss of no more than 3.1% when exposed to a given ketone concentration for 2 weeks,
wherein the inner layer is disposed upon the first working electrode and the first active area, and the outer layer disposed upon the inner layer and upon the second working electrode and the second active area, and
wherein the first membrane polymer comprises a crosslinked polyvinylpyridine homopolymer or copolymer,
wherein the sensor is configured to be partially inserted into a tissue.

14. The analyte sensor of claim 13 , wherein the first membrane polymer and the second membrane polymer differ from one another.

15. The analyte sensor of claim 13 , wherein the signal from the first active area and the signal from the second active area sensor increase linearly as functions of analyte concentrations.

16. The analyte sensor of claim 15 , wherein the signal from the first active area increases linearly as a function of a first analyte concentration from 0 mM to 10 mM.

17. The analyte sensor of claim 15 , wherein the signal from the first active area increases linearly as a function of a first analyte concentration from 0 mM to 5 mM.

18. The analyte sensor of claim 15 , wherein the signal from the second active area increases linearly as a function of a second analyte concentration from 0 mM to 30 mM.

19. The analyte sensor of claim 15 , wherein the signals that increase linearly each have a sensitivity of about 1 nA/mM.

20. The analyte sensor of claim 15 , wherein the signals that increase linearly each have an R 2 value of at least 0.96.

21. The analyte sensor of claim 15 , wherein the signals that increase linearly each have an R 2 value of at least 0.99.

22. The analyte sensor of claim 13 , wherein the second active area includes a glucose-responsive enzyme.

23. The analyte sensor of claim 13 , wherein each signal varies a few tenths of a nA or less from an initial signal over 190 hours at a given analyte concentration.

24. The analyte sensor of claim 13 , wherein the signal from the first active area has a mean signal loss of no more than 3.1% when exposed to 8 mM of β-hydroxybutyrate in 100mM PBS at 33° C. for 2 weeks.

Assignees

• Abbott Diabetes Care Inc

Inventors

• Oja Stephen
• Ouyang Tianmei
• Cho Hyun
• Tran Lam N
• Feldman Benjamin J

Classifications

• G01N27/3271

  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 title

• A61B5/6848

  Needles · CPC title

• A61B5/6846

  specially adapted to be brought in contact with an internal body part, i.e. invasive · CPC title

• A61B5/14546

  for measuring analytes not otherwise provided for, e.g. ions, cytochromes · CPC title

• A61B5/14532

  for measuring glucose, e.g. by tissue impedance measurement · CPC title