Cationic polymer based wired enzyme formulations for use in analyte sensors
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.
1. A glucose-responsive composition comprising:
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.
2. The composition of claim 1 , wherein the glucose-responsive enzyme is glucose oxidase (GOx).
3. The composition of claim 1 , wherein the glucose-responsive enzyme is glucose dehydrogenase (GDH).
4. The composition of claim 3 , wherein the glucose dehydrogenase is associated with a co-factor.
5. The composition of claim 4 , wherein the co-factor is flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), or pyrroloquinoline quinone (PQQ).
6. The composition of claim 1 , wherein the glucose-responsive enzyme comprises a complex of glucose dehydrogenase (GDH) and flavin adenine dinucleotide (FAD).
7. The composition of claim 1 , wherein the redox mediator comprises ferricyanide, phenanthroline quinone, or ferrocene.
8. The composition of claim 1 , wherein the redox mediator comprises a transition metal complex.
9. The composition of claim 8 , wherein the transition metal complex comprises osmium.
10. The composition of claim 9 , 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 or +1 to +5 indicating a positive or negative 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.
11. The composition of claim 10 , 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.
12. The composition of claim 11 , 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.