Analyte sensors and sensing methods for detecting creatinine

1 . An analyte sensor comprising:

at least a first working electrode;

a creatinine-responsive active area disposed on a distal end of the first working electrode, the creatinine-responsive active area comprising a first electron transfer agent, a first polymer, and an enzyme system comprising multiple enzymes that are capable of acting in concert to facilitate detection of creatinine, the enzyme system comprising:

creatinine amidohydrolase,

creatine amidinohydrolase, and

sarcosine oxidase;

a dielectric layer covering the first working electrode other than the distal end of the first working electrode;

a first membrane that is permeable to creatinine and overcoats the creatinine-responsive active area, the first membrane comprising polyvinylpyridine-co-styrene; and

an area for oxygen scavenging disposed upon the first membrane and isolated from the first working electrode, the area for oxygen scavenging comprising glucose oxidase as an oxygen scavenger,

wherein the sensor is configured to be partially inserted into a tissue such that a distal portion of the sensor is in contact with an interstitial fluid to detect creatinine in vivo.

2 . The analyte sensor of claim 1 , wherein the area for oxygen scavenging further comprises a second polymer and the glucose oxidase is covalently bonded to the second polymer.

3 . The analyte sensor of claim 1 , wherein the creatinine amidohydrolase, the creatine amidinohydrolase, and the sarcosine oxidase are each covalently bonded to the first polymer.

4 . The analyte sensor of claim 1 , further comprising:

a second working electrode;

a glucose-responsive active area disposed upon a surface of the second working electrode, the glucose-responsive active area comprising a second electron transfer agent, a third polymer, and glucose oxidase that is covalently bonded to the third polymer; and

a second membrane that is permeable to glucose and overcoats the glucose-responsive active area.

5 . The analyte sensor of claim 4 , wherein the first membrane and the second membrane are compositionally the same.

6 . An analyte sensor comprising:

a first working electrode and a second working electrode;

a creatinine-responsive active area disposed on a distal end of the first working electrode, the creatinine-responsive active area comprising a first electron transfer agent, a first polymer, and an enzyme system comprising multiple enzymes that are capable of acting in concert to facilitate detection of creatinine, the enzyme system comprising:

creatinine amidohydrolase,

creatine amidinohydrolase, and

sarcosine oxidase;

a dielectric layer covering the first working electrode other than the distal end of the first working electrode;

a first membrane that is permeable to creatinine and overcoats the creatinine-responsive active area, the first membrane comprising polyvinylpyridine-co-styrene;

an area for oxygen scavenging disposed upon the first membrane and isolated from the first working electrode, the area for oxygen scavenging comprising a second polymer and glucose oxidase as an oxygen scavenger, the glucose oxidase covalently bonded to the second polymer;

a glucose-responsive active area disposed upon a surface of the second working electrode, the glucose-responsive active area comprising a second electron transfer agent, a third polymer, and glucose oxidase that is covalently bonded to the third polymer; and

a second membrane that is permeable to glucose and overcoats the glucose-responsive active area,

wherein the sensor is configured to be partially inserted into a tissue such that a distal portion of the sensor is in contact with an interstitial fluid to detect glucose and creatinine in vivo.

7 . The analyte sensor of claim 6 , wherein the area for oxygen scavenging is overcoated by a third membrane that is also permeable to creatinine.

8 . The analyte sensor of claim 7 , wherein the first membrane, the second membrane and the third membrane are compositionally the same.

9 . The analyte sensor of claim 6 , wherein the first membrane and the second membrane are compositionally the same.

10 . The analyte sensor of claim 6 , wherein the creatinine amidohydrolase, the creatine amidinohydrolase, and the sarcosine oxidase are each covalently bonded to the first polymer.

11 . A method comprising:

exposing the analyte sensor of claim 1 to a fluid comprising at least creatinine;

applying a potential to the first working electrode;

obtaining a first signal at or above an oxidation-reduction potential of the creatinine-responsive active area, the first signal being proportional to a concentration of creatinine in the fluid; and

correlating the first signal to the concentration of creatinine in the fluid.

12 . The method of claim 11 , wherein the creatinine amidohydrolase, the creatine amidinohydrolase, and the sarcosine oxidase are each covalently bonded to the first polymer.

13 . The method of claim 11 , wherein the area for oxygen scavenging further comprises a second polymer and the glucose oxidase is covalently bonded to the second polymer.

14 . The method of claim 12 , wherein the sensor further comprises a second working electrode having a glucose-responsive active area disposed upon a surface of the second working electrode, the glucose-responsive active area comprising a second electron transfer agent, a third polymer, and glucose oxidase that is covalently bonded to the third polymer, the method further comprising:

applying a potential to the second working electrode;

obtaining a second signal at or above an oxidation-reduction potential of the glucose-responsive active area, the second signal being proportional to a concentration of glucose in the fluid; and

correlating the second signal to the concentration of glucose in the fluid.

15 . The method of claim 14 , wherein the first signal and the second signal are obtained at different times.

16 . The method of claim 14 , wherein the first signal and the second signal are obtained simultaneously via a first channel and a second channel.