Analyte sensors employing multiple enzymes and methods associated therewith
Methods and analyte sensors including at least a first working electrode having a first active area thereon, and performing a dip coating operation to deposit a bilayer membrane upon the first working electrode and the first active area. The bilayer may include an inner layer having a first membrane polymer and an outer layer having a second membrane polymer, the first membrane polymer and the second membrane polymer differing from one another. The dip coating operation may comprise one or more first dips in a first membrane formulation to form the inner layer of the bilayer membrane and one or more second dips in a second membrane formulation to form the outer layer of the bilayer membrane upon the inner layer.
1 . A sensor control device for detecting glucose and ketones in vivo, the sensor control device comprising:
(a) a sensor comprising:
a substrate with a first face and a second face;
a reference electrode;
a first working electrode, wherein a ketones-responsive active area is disposed upon a surface of the first working electrode;
a second working electrode, wherein a glucose-responsive active area is disposed upon a surface of the second working electrode, wherein the electrodes are electrically isolated from one another by a dielectric material; and
a mass transport limiting membrane overcoating the ketones-responsive active area and the glucose-responsive active area, the mass transport limiting membrane providing variable analyte permeability at each of the ketones-responsive active area and the glucose-responsive active area;
wherein the mass transport limiting membrane overcoating at least the ketones-responsive active area comprises a multi-component membrane; and
wherein the sensor is configured to be partially inserted into a user's skin such that a distal portion of the sensor is in contact with an interstitial fluid to detect glucose and ketones in vivo; and
(b) sensor electronics.
2 . The sensor control device of claim 1 , wherein the first and second working electrodes are independently disposed on the first and second faces of the substrate.
3 . The sensor control device of claim 1 , wherein the first working electrode and the second working electrode are located on opposite faces of the substrate, and wherein the ketones-responsive active area and the glucose-responsive active area are laterally spaced apart.
4 . The sensor control device of claim 1 , wherein the first working electrode and the second working electrode are each located on the first face or the second face of the substrate, and wherein the ketones-responsive active area and the glucose-responsive active area are vertically spaced apart.
5 . The sensor control device of claim 3 , further comprising a counter electrode.
6 . The sensor control device of claim 5 , wherein the reference electrode and the counter electrode are located on opposite faces of the substrate.
7 . The sensor control device of claim 4 , further comprising a counter electrode.
8 . The sensor control device of claim 7 , wherein the reference electrode and the counter electrode are each located on the first or second face of the substrate.
9 . The sensor control device of claim 1 , wherein the ketones-responsive active area comprises a first polymer and an enzyme system comprising nicotinamide adenine dinucleotide (NAD) and at least two enzymes that facilitate detection of ketones.
10 . The sensor control device of claim 9 , wherein the glucose-responsive active area comprises a second polymer and a glucose-responsive enzyme.
11 . The sensor control device of claim 1 , wherein the multi-component membrane disposed upon the ketone-responsive active area comprises two or more different membrane polymers.
12 . The sensor control device of claim 11 , wherein the multi-component membrane disposed upon the ketone-responsive active area comprises at least a bilayer membrane.
13 . The sensor control device of claim 11 , wherein the mass transport limiting membrane has a thickness over the ketones-responsive active area that differs from a thickness of the mass transport limiting membrane over the glucose-responsive active area.
14 . The sensor control device of claim 11 , wherein the mass transport limiting membrane has a composition over the ketones-responsive active area that differs from a composition of the mass transport limiting membrane over the glucose-responsive active area.
15 . The sensor control device of claim 14 , wherein:
the mass transport limiting membrane comprises a first portion overcoating the ketones-responsive active area and a second portion overcoating the glucose-responsive active area; wherein
the first portion comprises a first membrane polymer and a second membrane polymer that differ from each other; and wherein
the second portion comprises the first membrane polymer or the second membrane polymer.
16 . The sensor control device of claim 15 , wherein the first membrane polymer comprises a crosslinked polyvinylpyridine homopolymer or copolymer.
17 . The sensor control device of claim 16 , wherein the second membrane polymer comprises a crosslinked polyvinylpyridine-co-styrene polymer.
18 . The sensor control device of claim 14 , wherein the ketones-responsive and glucose-responsive active areas each comprises at least one sensing spot, and the ketones-responsive and glucose-responsive active areas each range in size from about 0.01 mm 2 to about 1 mm 2 .
19 . The sensor control device of claim 9 , wherein the enzyme system comprises β-hydroxybutyrate dehydrogenase and diaphorase.
20 . The sensor control device of claim 10 , wherein the glucose-responsive enzyme comprises glucose oxidase.
21 . The sensor control device of claim 9 , wherein the ketones-responsive active area comprises a first electron transfer agent.
22 . The sensor control device of claim 10 , wherein the glucose-responsive active area comprises a second electron transfer agent.
23 . The sensor control device of claim 1 , wherein the first working electrode is configured to independently generate a first signal indicative of β-hydroxybutyrate concentration, and wherein the second working electrode is configured to independently generate a second signal indicative of glucose concentration.
24 . The sensor control device of claim 23 , wherein the first signal and second signal are measured simultaneously via a first channel and a second channel, respectively.
25 . The sensor control device of claim 23 , wherein the sensor electronics are configured to determine a ketone concentration and glucose concentration based on the first and second signals using a calibration curve for each analyte.
26 . An analyte sensing system for detecting glucose and ketones in vivo comprising the sensor control device of claim 1 .
27 . The analyte sensing system of claim 26 , further comprising a reader device.