Analyte sensors and sensing methods featuring low-potential detection

Patent metadata

Field	Value
Publication number	US-12044648-B2
Application number	US-202017132360-A
Country	US
Kind code	B2
Filing date	Dec 23, 2020
Priority date	Dec 23, 2019
Publication date	Jul 23, 2024
Grant date	Jul 23, 2024

Abstract

Analyte sensors responsive at low working electrode potentials may comprise an active area upon a surface of a working electrode, wherein the active area comprises a polymer, a redox mediator covalently bonded to the polymer, and at least one analyte-responsive enzyme covalently bonded to the polymer. A specific redox mediator responsive at low potential may have a structure of

wherein G is a linking group covalently bonding the redox mediator to the polymer. A mass transport limiting membrane permeable to the analyte may overcoat the active area. In some sensor configurations, the mass transport limiting membrane may comprise a membrane polymer crosslinked with a branched crosslinker comprising three or more crosslinkable groups, such as polyethylene glycol tetraglycidyl ether.

First claim

What is claimed is the following:

1. An analyte sensor comprising:
a sensor tail comprising:
i) a Ag/AgCl reference electrode;
ii) at least a first working electrode and a second working electrode;
iii) a first active area disposed upon a surface of the first working electrode and responsive at low potential to β-hydroxybutyrate, the first active area comprising a first polymer, a first redox mediator covalently bonded to the first polymer, and at least one enzyme responsive to β-hydroxybutyrate covalently bonded to the first polymer;
wherein the low potential is above an oxidation-reduction potential of the first redox mediator and below about −80 mV relative to the Ag/AgCl reference electrode;
wherein the oxidation-reduction potential of the first redox mediator ranges from about −200 mV to about −400 mV relative to the Ag/AgCl reference electrode;
wherein the first redox mediator has a structure of

wherein G is a linking group covalently bonding the first redox mediator to the first polymer; and

iv) a second active area disposed upon a surface of the second working electrode and responsive to a second analyte differing from β-hydroxybutyrate, the second active area comprising a second polymer, a second redox mediator differing from the first redox mediator covalently bonded to the second polymer, and at least one enzyme responsive to the second analyte covalently bonded to the second polymer;
wherein the at least one enzyme responsive to the second analyte comprises an enzyme system comprising multiple enzymes that are collectively responsive to the second analyte;

v) a mass transport limiting membrane permeable to 3-hydroxybutyrate that overcoats at least the first active area;
wherein a second portion of the mass transport limiting membrane overcoats the second active area.

2. The analyte sensor of claim 1 , wherein the at least one enzyme comprises an enzyme system comprising multiple enzymes that are collectively responsive to β-hydroxybutyrate.

3. The analyte sensor of claim 1 , wherein the mass transport limiting membrane comprises a membrane polymer crosslinked with a branched crosslinker comprising three or more crosslinkable groups.

4. The analyte sensor of claim 3 , wherein the membrane polymer comprises a polyvinylpyridine or a polyvinylimidazole.

5. The analyte sensor of claim 3 , wherein the branched crosslinker comprises polyethyleneglycol tetraglycidyl ether.

6. A method comprising:
exposing an analyte sensor to a fluid comprising β-hydroxybutyrate, the analyte sensor comprising:
a sensor tail comprising:
i) a Ag/AgCl reference electrode;
ii) at least a first working electrode;
iii) a first active area disposed upon a surface of the first working electrode and responsive at low potential to β-hydroxybutyrate, the first active area comprising a first polymer, a first redox mediator covalently bonded to the first polymer, and at least one enzyme responsive to β-hydroxybutyrate covalently bonded to the first polymer;
wherein the at least one enzyme comprises an enzyme system comprising multiple enzymes that are collectively responsive to β-hydroxybutyrate;
wherein the low potential is above an oxidation-reduction potential of the first redox mediator and below about −80 mV relative to the Ag/AgCl reference electrode;
wherein the oxidation-reduction potential of the first redox mediator ranges from about −200 mV to about −400 mV relative to the Ag/AgCl reference electrode;
wherein the first redox mediator has a structure of

wherein G is a linking group covalently bonding the first redox mediator to the first polymer; and

iv) a mass transport limiting membrane permeable to β-hydroxybutyrate that overcoats at least the first active area;

applying the low potential to the first working electrode;
obtaining a first signal at or above an oxidation-reduction potential of the first active area, the first signal being proportional to a concentration of β-hydroxybutyrate in a fluid contacting the first active area; and
correlating the first signal to the concentration of β-hydroxybutyrate in the fluid.

7. The method of claim 6 , wherein the mass transport limiting membrane comprises a membrane polymer crosslinked with a branched crosslinker comprising three or more crosslinkable groups.

8. The method of claim 7 , wherein the membrane polymer comprises a polyvinylpyridine or a polyvinylimidazole.

9. The method of claim 7 , wherein the branched crosslinker comprises polyethyleneglycol tetraglycidyl ether.

10. The method of claim 6 , wherein the analyte sensor further comprises:
a second working electrode; and
a second active area disposed upon a surface of the second working electrode responsive to a second analyte differing from β-hydroxybutyrate, the second active area comprising a second polymer, a second redox mediator differing from the first redox mediator, the second redox mediator covalently bonded to the second polymer, and at least one enzyme responsive to the second analyte covalently bonded to the second polymer;
wherein a second portion of the mass transport limiting membrane overcoats the second active area.

11. The method of claim 10 , wherein the at least one enzyme responsive to the second analyte comprises an enzyme system comprising multiple enzymes that are collectively responsive to the second analyte.

12. A method comprising:
exposing an analyte sensor to a fluid comprising β-hydroxybutyrate, the analyte sensor comprising:
a sensor tail comprising:
i) a Ag/AgCl reference electrode; and
ii) at least a first working electrode and a second working electrode;
iii) a first active area disposed upon a surface of the first working electrode and responsive at low potential to β-hydroxybutyrate, the first active area comprising a first polymer, a first redox mediator covalently bonded to the first polymer, and at least one enzyme responsive to β-hydroxybutyrate covalently bonded to the first polymer;
wherein the low potential is above an oxidation-reduction potential of the first redox mediator and below about −80 mV relative to the Ag/AgCl reference electrode;
wherein the oxidation-reduction potential of the first redox mediator ranges from about −200 mV to about −400 mV relative to the Ag/AgCl reference electrode;
wherein the first redox mediator has a structure of

wherein G is a linking group covalently bonding the first redox mediator to the first polymer; and

iv) a second active area disposed upon a surface of the second working electrode and responsive to a second analyte differing from β-hydroxybutyrate, the second active area comprising a second polymer, a second redox mediator differing from the first redox mediator covalently bonded to the second polymer, and at least one enzyme responsive to the second analyte covalently bonded to the second polymer;
wherein the at least one enzyme responsive to the second analyte comprises an enzyme system comprising multiple enzymes that are collectively responsive to the second analyte

v) a mass transport limiting membrane permeable to β-hydroxybutyrate that overcoats at least the first active area;
wherein a second portion of the mass transport limiting me

Assignees

• Abbott Diabetes Care Inc

Inventors

• Latour John V
• Mccanless Jonathan D
• Oja Stephen
• Ouyang Tianmei
• Wallis Kevin Paul
• Feldman Benjamin J
• Hoss Udo
• Qian Suyue

Classifications

• A61B5/14532

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

• A61B5/1473

  invasive, e.g. introduced into the body by a catheter · CPC title

• G01N27/3275

  Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction · CPC title

• G01N27/26 Primary

  by investigating electrochemical variables; by using electrolysis or electrophoresis · CPC title

• G01N27/3277

  being a redox reaction, e.g. detection by cyclic voltammetry (voltammetry per se G01N27/42, G01N27/48) · CPC title