Stabilized lactate responsive enzymes, electrodes and sensors, and methods for making and using the same

Patent metadata

Field	Value
Publication number	US-9914952-B2
Application number	US-201615183488-A
Country	US
Kind code	B2
Filing date	Jun 15, 2016
Priority date	Jun 15, 2015
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

Embodiments of the present disclosure relate to stabilized lactate oxidase compositions, and electrodes, sensors and systems that include the same. Also provided are methods for making the compositions and for detecting and/or measuring lactate in vivo with stable lactate enzyme compositions.

First claim

That which is claimed is:

1. A lactate sensor comprising an enzyme composition that comprises:
a lactate responsive enzyme; and
a stabilizing agent that stabilizes the lactate responsive enzyme in a manner sufficient to provide a sensor signal that changes by 10% or less for 60 continuous hours or more,
wherein the lactate responsive enzyme is lactate oxidase and the stabilizing agent is catalase, present in the enzyme composition in a weight (w/w) ratio of lactate oxidase to catalase ranging from 10 to 1 to 2 to 1.

2. The lactate sensor according to claim 1 , wherein the enzyme composition comprises a heterocycle-containing polymer and a crosslinker.

3. The lactate sensor according to claim 2 , wherein the lactate responsive enzyme and stabilizing agent are crosslinked within the polymer.

4. The lactate sensor according to claim 2 , wherein the lactate responsive enzyme and stabilizing agent are covalently bonded to the polymer.

5. The lactate sensor according to claim 1 , wherein the stabilizing agent stabilizes the lactate responsive enzyme in a manner sufficient to provide a sensor signal that changes by 10% or less for 168 continuous hours or more.

6. The lactate sensor according to claim 5 , wherein the stabilizing agent stabilizes the lactate responsive enzyme in a manner sufficient to provide a sensor signal that changes by 5% or less for 168 continuous hours or more.

7. The lactate sensor according to claim 1 , wherein the stabilizing agent increases sensor sensitivity to lactate as compared to a lactate sensor that does not include the stabilizing agent.

8. The lactate sensor according to claim 7 , wherein the stabilizing agent increases sensor sensitivity to lactate for 60 continuous hours or more.

9. The lactate sensor according to claim 8 , wherein the stabilizing agent increases sensor sensitivity by 10% or more as compared to a lactate sensor that does not include the stabilizing agent.

10. The lactate sensor according to claim 1 , wherein the enzyme composition further comprises an electron transfer agent.

11. The lactate sensor according to claim 10 , wherein the electron transfer agent is an osmium-containing complex.

12. The lactate sensor according to claim 10 , wherein the electron transfer agent is covalently bonded to the polymer.

13. The lactate sensor according to claim 1 , wherein the lactate sensor comprises a working electrode and a counter electrode.

14. The lactate sensor according to claim 13 , wherein the enzyme composition is positioned proximate to a working electrode.

15. The lactate sensor according to claim 14 , wherein the enzyme composition is fixed to the working electrode.

16. The lactate sensor according to claim 1 , wherein the lactate oxidase is present in the enzyme composition in an amount ranging from 0.05 μg to 5 μg.

17. The lactate sensor according to claim 1 , wherein the catalase is present in the enzyme composition in an amount ranging from 0.05 μg to 2 μg.

18. The lactate sensor according to claim 1 , wherein the stabilizing agent stabilizes the lactate responsive enzyme in a manner such that the lactate sensor exhibits a decrease in sensor output of 2 nA or less during exposure to lactate as compared to a lactate sensor that does not include the stabilizing agent.

19. The lactate sensor according to claim 1 , wherein the stabilizing agent increases sensor sensitivity to lactate in an amount ranging from 1 nA/mg/dL to 15 nA/mg/dL or more as compared to a lactate sensor that does not include the stabilizing agent.

20. A lactate sensor comprising an enzyme composition that comprises:
a polymer;
a lactate responsive enzyme; and
a stabilizing agent,
wherein the lactate responsive enzyme is lactate oxidase and the stabilizing agent is catalase, present in the enzyme composition in a weight (w/w) ratio of lactate oxidase to catalase ranging from 10 to 1 to 2 to 1, and
wherein the catalase is covalently bonded to the polymer.

Assignees

• Abbott Diabetes Care Inc

Inventors

• Ouyang Tianmei
• Feldman Benjamin J
• Chen Kuan-Chou

Classifications

• C12Q1/005 Primary

  involving specific analytes or enzymes (including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence) · CPC title

• C12Y111/01006

  Catalase (1.11.1.6) · CPC title

• C12Y113/12004

  Lactate 2-monooxygenase (1.13.12.4) · CPC title

• C12N9/96

  Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates · CPC title

• C12N9/0065

  acting on hydrogen peroxide as acceptor (1.11) · CPC title