Analyte sensor incorporating negatively charged moieties

1. A crosslinked, hydrophilic copolymer comprising:

backbone chains comprising:

first methacrylate-derived units, each having a hydrophilic side chain;

second methacrylate-derived units having the structure of formula (III):

wherein

L is absent, C 1 -C 6 alkyl, —Y—C 1 -C 6 alkyl or a hydrophilic group, where Y is —O—, —NR′— or —S—; and

R n is —S − , —N(R′) − , —C(O)O − , —N(R′)C(O)O − , —S(O)(R′) − , —S(O)O − , —P(O)(OR′)O − , —P(O)(R′)O − , —P(O)(NR′ 2 )O − , —P(O)(NR′ 2 )(NR′) − , —P(O)(R′)(NR′) − , —P(O)(OR′)(NR′) − , —OP(O)(OR′)O − , —OP(O)(R′)O − , —OP(O)(NR′ 2 )O − , —OP(O)(NR′ 2 )(NR′) − , —OP(O)(R′)(NR′) − , —OP(O)(OR′)(NR′), —P(O)O 2 2− , —P(O)(NR′) 2 2− , —OP(O)O 2 2− , —OP(O)(NR′) 2 2− or a salt thereof, wherein R′ is hydrogen or —C 1 -C 12 alkyl;

or the structure of formula (IIIa)

wherein

Y is —O—, —NR′— or —S—;

u is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and

R n is —S − , —N(R′) − , —C(O)O − , —N(R′)C(O)O − , —S(O)(R′) − , —S(O)O − , —P(O)(OR′)O − , —P(O)(R′)O − , —P(O)(NR′ 2 )O − , —P(O)(NR′ 2 )(NR′) − , —P(O)(R′)(NR′) − , —P(O)(OR′)(NR′) − , —OP(O)(OR′)O − , —OP(O)(R′)O − , —OP(O)(NR′ 2 )O − , —OP(O)(NR′ 2 )(NR′) − , —OP(O)(R′)(NR′) − , —OP(O)(OR′)(NR′), —P(O)O 2 2− , —P(O)(NR′) 2 2− , —OP(O)O 2 2− , —OP(O)(NR′) 2 2− or a salt thereof, wherein R′ is hydrogen or —C 1 -C 12 alkyl;

third methacrylate-derived units; and

hydrophilic crosslinks between third methacrylate-derived units in different backbone chains.

2. An analyte sensor comprising:

an analyte sensing component embedded within the crosslinked, hydrophilic copolymer of claim 1 , wherein the crosslinked, hydrophilic copolymer is adjacent to an electrode.

3. The analyte sensor claim 2 , wherein the analyte sensing component comprises glucose oxidase.

4. An analyte sensor comprising:

a sensing membrane comprising:

a crosslinked network comprising one or more proteins and crosslinks, wherein the proteins are crosslinked through carbon-nitrogen double bonds between amine group nitrogen atoms on the proteins and carbon atoms on the crosslinks, and an analyte sensing component embedded in the crosslinked network; and

a crosslinked, hydrophilic copolymer of claim 1 ,

wherein the sensing membrane is adjacent to an electrode.

5. The analyte sensor of claim 4 , wherein the sensing membrane is between the electrode and the crosslinked, hydrophilic copolymer.

6. The analyte sensor of claim 2 , wherein the first methacrylate-derived units have the structure of formula (Ia):

wherein

X is —O—, —NR′— or —S—;

y is 0-10; and

R 1 is hydrogen, —C 1 -C 12 alkyl, —C 1 -C 12 alkyl-OH, —SiR′ 3 , —C(O)—C 1 -C 12 alkyl, —C 1 -C 12 alkyl-C(O)OR′, wherein R′ is —C 1 -C 12 alkyl.

7. The analyte sensor of claim 6 , wherein the first methacrylate-derived units have the structure:

8. The analyte sensor of claim 2 , wherein L is C 1 -C 6 alkyl or —O—C 1 -C 6 alkyl, where C 1 -C 6 alkyl is methylene, ethylene, propylene, butylene, pentylene or hexylene.

9. The analyte sensor of claim 2 , wherein the second methacrylate-derived units have the structure of formula (IIIa):

wherein

Y is —O—, —NR′— or —S—;

u is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and

R n is —S − , —N(R′) − , —C(O)O − , —N(R′)C(O)O − , —S(O)(R′) − , —S(O)O − , —P(O)(OR′)O − , —P(O)(R′)O − , —P(O)(NR′ 2 )O − , —P(O)(NR′ 2 )(NR′) − , —P(O)(R′)(NR′) − , —P(O)(OR′)(NR′) − , —OP(O)(OR′)O − , —OP(O)(R′)O − , —OP(O)(NR′ 2 )O − , —OP(O)(NR′ 2 )(NR′) − , —OP(O)(R′)(NR′) − , —OP(O)(OR′)(NR′), —P(O)O 2 2− , —P(O)(NR′) 2 2− , —OP(O)O 2 2− , —OP(O)(NR′) 2 2− or a salt thereof, wherein R′ is hydrogen or —C 1 -C 12 alkyl.

10. The analyte sensor of claim 2 , further comprising fourth methacrylate-derived units, each having a hydrophilic side chain that is different than the hydrophilic side chain of the first methacrylate-derived unit.

11. The analyte sensor of claim 10 , wherein the fourth methacrylate-derived units have the structure of formula (II):

wherein

Y is —O—, —NR′— or —S—;

R 2 is hydrogen, —C 1 -C 12 alkyl, —SiR′ 3 , —C(O)—C 1 -C 12 alkyl or —C 1 -C 12 alkyl-C(O)OR′, wherein R′ is hydrogen or —C 1 -C 12 alkyl; and

x is 1-10.

12. The analyte sensor of 10 , wherein the fourth methacrylate-derived units have the structure of formula (II):

wherein

Y is —O—, —NR′— or —S—;

R 2 is hydrogen, —C 1 -C 12 alkyl, —SiR′ 3 , —C(O)—C 1 -C 12 alkyl or —C 1 -C 12 alkyl-C(O)OR′, where R′ is hydrogen or —C 1 -C 12 alkyl; and

x is an average value of from 2 to about 250.

13. The analyte sensor of claim 10 , wherein

the first methacrylate-derived units are derived from 2-hydroxyethylmethacrylate;

the fourth methacrylate-derived units have the structure of formula (II):

wherein x is an average value of from about 10 to about 15;

the hydrophilic crosslinks have the structure of formula (IVa):

wherein w is 1; and

the analyte sensing component comprises glucose oxidase.

14. The analyte sensor of claim 4 , wherein in the crosslinks are C 2 -C 6 alkyl.

15. The analyte sensor of claim 4 , wherein the proteins are bovine serum albumin.

16. The analyte sensor according to claim 4 , wherein the analyte sensing component comprises glucose oxidase.

17. The analyte sensor of claim 4 , wherein the crosslinked, hydrophilic copolymer further comprises fourth methacrylate-derived units, each having a hydrophilic side chain that is different than the hydrophilic side chains of the first methacrylate-derived unit.

18. The analyte sensor of claim 17 , wherein

the proteins are BSA;

the crosslinks are C 2 -C 6 alkyl;

the analyte sensing component comprises glucose oxidase;

the first methacrylate-derived units are derived from 2-hydroxyethylmethacrylate;

the fourth methacrylate-derived units have the structure of formula (II):

wherein x is an average value of from about 10 to about 15; and

the hydrophilic crosslinks have the structure of formula (IVa):

wherein w is 1.

19. The analyte sensor of claim 2 , wherein the second methacrylate-derived units have the structure of formula (III):

wherein

L is absent, C 1 -C 6 alkyl or —Y—C 1 -C 6 alkyl, where Y is —O—, —NR′— or —S—; and

R n is —S − , —N(R′) − , —C(O)O − , —N(R′)C(O)O − , —S(O)(R′) − , —S(O)O − , —P(O)(OR′)O − , —P(O)(R′)O − , —P(O)(NR′ 2 )O − , —P(O)(NR′ 2 )(NR′) − , —P(O)(R′)(NR′) − , —P(O)(OR′)(NR′) − , —OP(O)(OR′)O − , —OP(O)(R′)O − , —OP(O)(NR′ 2 )O − , —OP(O)(NR′ 2 )(NR′) − , —OP(O)(R′)(NR′) − , —OP(O)(OR′)(NR′), —P(O)O 2 2− , —P(O)(NR′) 2 2− , —OP(O)O 2 2− , —OP(O)(NR′) 2 2− or a salt thereof, wherein R′ is hydrogen or —C 1 -C 12 alkyl.

20. The analyte sensor of claim 4 , wherein the second methacrylate-derived units have the structure of formula (III):

wherein

L is absent, C 1 -C 6 alkyl or —Y—C 1 -C 6 alkyl, where Y is —O—, —NR′— or —S—; and

R n is —S − , —N(R′) − , —C(O)O − , —N(R′)C(O)O − , —S(O)(R′) − , —S(O)O − , —P(O)(OR′)O − , —P(O)(R′)O − , —P(O)(NR′ 2 )O − , —P(O)(NR′ 2 )(NR′) − , —P(O)(R′)(NR′) − , —P(O)(OR′)(NR′) − , —OP(O)(OR′)O − , —OP(O)(R′)O − , —OP(O)(NR′ 2 )O − , —OP(O)(NR′ 2 )(NR′) − , —OP(O)(R′)(NR′) − , —OP(O)(OR′)(NR′), —P(O)O 2 2− , —P(O)(NR′) 2 2− , —OP(O)O 2 2− , —OP(O)(NR′) 2 2− or a salt thereof, wherein R′ is hydrogen or —C 1 -C 12 alkyl.

21. The analyte sensor of claim 4 , wherein the second methacrylate-derived units have the structure of formula (IIIa):

wherein

Y is —O—, —NR′— or —S—;

u is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and

R n is —S − , —N(R′) − , —C(O)O − , —N(R′)C(O)O − , —S(O)(R′) − , —S(O)O − , —P(O)(OR′)O − , —P(O)(R′)O − , —P(O)(NR′ 2 )O − , —P(O)(NR′ 2 )(NR′) − , —P(O)(R′)(NR′) − , —P(O)(OR′)(NR′) − , —OP(O)(OR′)O − , —OP(O)(R′)O − , —OP(O)(NR′ 2 )O − , —OP(O)(NR′ 2 )(NR′) − , —OP(O)(R′)(NR′) − , —OP(O)(OR′)(NR′), —P(O)O 2 2− , —P(O)(NR′) 2 2− , —OP(O)O 2 2− , —OP(O)(NR′) 2 2− or a salt thereof, wherein R′ is hydrogen or —C 1 -C 12 alkyl.