Cationic polymer based wired enzyme formulations for use in analyte sensors

Patent metadata

Field	Value
Publication number	US-9428785-B2
Application number	US-201414558509-A
Country	US
Kind code	B2
Filing date	Dec 2, 2014
Priority date	Sep 15, 2008
Publication date	Aug 30, 2016
Grant date	Aug 30, 2016

Abstract

Embodiments of the invention include analyte-responsive compositions and electrochemical analyte sensors having a sensing layer that includes an analyte-responsive enzyme and a cationic polymer. Also provided are systems and methods of making the sensors and using the electrochemical analyte sensors in analyte monitoring.

First claim

That which is claimed is:

1. An analyte sensor assembly, comprising:
an electrochemical sensor comprising:
a substrate comprising a working electrode and a counter electrode or a counter/reference electrode;
a sensing layer disposed on the working electrode, wherein the sensing layer comprises a glucose-responsive enzyme, a cationic polymer selected from the group consisting of polyallylamine (PAH), polyethyleneimine (PEI), poly(L-lysine) (PLL), or poly(L-arginine) (PLA), and a positively charged redox mediator non-covalently associated with the cationic polymer; and

a transmitter unit operatively coupled to the electrochemical sensor to receive signals from the electrochemical sensor corresponding to an analyte level of a subject.

2. The analyte sensor of claim 1 , wherein at least a portion of the sensor is adapted to be subcutaneously positioned in a subject.

3. The analyte sensor of claim 1 , wherein the analyte-responsive enzyme is glucose oxidase (GOx).

4. The analyte sensor of claim 1 , wherein the analyte-responsive enzyme is a dehydrogenase.

5. The analyte sensor of claim 4 , wherein the dehydrogenase is glucose dehydrogenase (GDH).

6. The analyte sensor of claim 5 , wherein the glucose dehydrogenase is associated with a co-factor.

7. The analyte sensor of claim 6 , wherein the co-factor is flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), or pyrroloquinoline quinone (PQQ).

8. The analyte sensor of claim 4 , wherein the dehydrogenase comprises a complex of glucose dehydrogenase (GDH) and flavin adenine dinucleotide (FAD).

9. The analyte sensor of claim 1 , further comprising a flux limiting layer disposed over at least a portion of the working electrode.

10. The analyte sensor of claim 1 , wherein the redox mediator comprises ferricyanide, phenanthroline quinone, or ferrocene.

11. The analyte sensor of claim 1 , wherein the redox mediator comprises a transition metal complex.

12. The analyte sensor of claim 11 , wherein the transition metal complex comprises osmium.

13. The analyte sensor of claim 1 , wherein the transition metal complex comprises the following formula:

wherein
(i) M is ruthenium, osmium, or vanadium; and
(ii) L is selected from the group consisting of:

wherein:
R 1 , R 2 , and R′ 1 are independently substituted or unsubstituted alkyl, alkenyl, or aryl groups;
R 3 , R 4 , R 5 , R 6 , R′ 3 , R′ 4 , R a , R b , R c , and R d are independently —H, —F, —Cl, —Br, —I, —NO 2 , —CN, —CO 2 H, —SO 3 H, —NHNH 2 , —SH, aryl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, —OH, alkoxy, —NH 2 , alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino, alkylthio, alkenyl, aryl, or alkyl;
c is an integer selected from +1 to +5 indicating a positive charge;
X represents at least one counter ion;
d is an integer from 1 to 5 representing the number of counter ions; and
L 1 , L 2 , L 3 and L 4 are ligands, wherein L 1 comprises a heterocyclic compound coupled a polymeric backbone; and wherein L 1 and L 2 in combination form a first bidentate ligand.

14. The analyte sensor of claim 13 , wherein the transition metal complex comprises the following formula:

wherein R 3 , R 4 , R 5 , R 6 , R a , R b , R c , R d , R′ 3 and R′ 4 are —H;
R 1 and R 2 are independently substituted or unsubstituted C1 to C12 alkyls; and
R 1 , R 2 , and R′ 1 are independently —H or substituted or unsubstituted C1-C12 alkoxy, C1-12 alkylthio, C1-C12 alkylamino, C2-C24 dialkylamino, or C1-C12 alkyl.

15. The analyte sensor of claim 14 , wherein at least one of R 1 , R 2 , and R′ 1 comprises a reactive group selected from the group consisting of carboxy, activated ester, sulfonyl halide, sulfonate ester, isocyanate, isothiocyanate, epoxide, aziridine, halide, aldehyde, ketone, amine, acrylamide, thiol, acyl azide, acyl halide, hydrazine, hydroxyamine, alkyl halide, imidazole, pyridine, phenol, alkyl sulfonate, halotriazine, imido ester, maleimide, hydrazide, hydroxy, and photo-reactive azido aryl groups.

Assignees

• Abbott Diabetes Care Inc

Inventors

• Feldman Benjamin J
• Ouyang Tianmei
• Liu Zenghe

Classifications

• G01N2333/904

  acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1) · CPC title

• C12Q1/006 Primary

  for glucose · CPC title

• G01N27/3272

  Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels (optical biosensors G01N33/52) · CPC title

• C12Q1/32

  involving dehydrogenase · CPC title

• C12Q1/004 Primary

  mediator-assisted · CPC title