# US 12,594,013 B2 · Analyte sensors and sensing methods featuring dual detection of glucose and ketones > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,594,013 B2 - Document ID: US12594013B2 - Status: Granted - Kind: B2 - Application number: 16/774,835 - Filed: 2020-01-28 - Published: 2020-07-30 - Granted: 2026-04-07 - Earliest claimed: 2019-01-28 - Assignees: Abbott Diabetes Care Inc. - Applicants: Abbott Diabetes Care Inc. - Inventors: Benjamin J. Feldman; Tianmei Ouyang; Stephen M. Oja; Lam Tran; Hyun Cho - Web page: https://patentgrep.com/patent/US12594013B2 ## CPC - A61B 5/14865: {invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors} - A61B 5/14532: {for measuring glucose, e.g. by tissue impedance measurement} - A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes} - A61L 31/041: {Mixtures of macromolecular compounds} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) ## Abstract Glucose and ketones may be dysregulated singularly or concurrently in certain physiological conditions and may be advantageously assayed together using an analyte sensor capable of detecting both analytes. Certain analyte sensors capable of dual detection may comprise a first working electrode and a second working electrode, a ketones-responsive active area disposed upon a surface of the first working electrode, a glucose-responsive active area comprising a glucose-responsive enzyme disposed upon a surface of the second working electrode, a membrane having a first portion overcoating the ketones-responsive active area and a second portion overcoating the glucose-responsive active area, in which the first portion and the second portion have different compositions. The ketones-responsive active area comprises an enzyme system comprising at least two enzymes that are capable of acting in concert to facilitate detection of ketones. ## Claims ### Claim 1 An electrochemical analyte sensor for detecting glucose and ketones in vivo, the sensor comprising: a first working electrode and a second working electrode; a ketones-responsive active area for detecting ketones, the ketones-responsive active area disposed directly upon a surface of the first working electrode, the ketones-responsive active area comprising a cofactor, a first polymer, and at least two enzymes covalently bound to the first polymer; a glucose-responsive active area for detecting glucose, the glucose-responsive active area disposed upon a surface of the second working electrode, the glucose-responsive active area comprising a second polymer and a glucose-responsive enzyme covalently bound to the second polymer; and a multi-component mass transport limiting membrane disposed over on the ketones-responsive active area, 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. ### Claim 2 (depends on 1) The analyte sensor of claim 1, wherein the ketones-responsive active area comprises an electron-transfer agent and the glucose-responsive active area comprises an electron-transfer agent. ### Claim 3 (depends on 2) The analyte sensor of claim 2, wherein the glucose-responsive enzyme is glucose oxidase or glucose dehydrogenase. ### Claim 4 (depends on 3) The analyte sensor of claim 3, wherein the at least two enzymes comprise β-hydroxybutyrate dehydrogenase and a nicotinamide adenine dinucleotide oxidase. ### Claim 5 (depends on 2) The analyte sensor of claim 2, wherein the electron-transfer agent in the glucose-responsive active area and the electron-transfer agent in the ketones-responsive active area are the same. ### Claim 6 (depends on 1) The sensor of claim 1, wherein the ketones-responsive active area is disposed closer to a distal end of the sensor than the glucose-responsive active area. ### Claim 7 (depends on 1) The analyte sensor of claim 1, wherein the multi-component mass transport limiting membrane comprises a first membrane for limiting diffusion of ketones to the ketones-responsive active area. ### Claim 8 (depends on 7) The analyte sensor of claim 7, wherein the multi-component mass transport limiting membrane further comprises a second membrane for limiting diffusion of glucose to the glucose-responsive active area disposed over the first membrane. ### Claim 9 (depends on 8) The analyte sensor of claim 8, wherein the second membrane is disposed over the glucose-responsive active area. ### Claim 10 (depends on 9) The analyte sensor of claim 9, wherein the first membrane and the second membrane have differing permeability to ketones. ### Claim 11 (depends on 10) The analyte sensor of claim 10, wherein the first and second membranes have different compositions. ### Claim 12 (depends on 11) The analyte sensor of claim 11, wherein the first membrane comprises polyvinylpyridine. ### Claim 13 (depends on 12) The sensor of claim 12, wherein the second membrane comprises polyvinylpyridine-co-styrene. ### Claim 14 An electrochemical analyte sensor for detecting glucose and ketones in vivo, the sensor comprising: a first working electrode and a second working electrode; a ketones-responsive active area for detecting ketones, the ketones-responsive active area disposed directly upon a surface of the first working electrode, the ketones-responsive active area comprising (i) a first polymer, (ii) at least two enzymes, and (iii) a cofactor; a glucose-responsive active area for detecting glucose, the glucose-responsive area disposed upon a surface of the second working electrode, the glucose-responsive active area comprising a second polymer and a glucose-responsive enzyme; and a multi-component mass transport limiting membrane comprising two or more membrane polymers disposed over the ketones-responsive active area, wherein the two or more membrane polymers have differing permeability to ketones, 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. ### Claim 15 (depends on 14) The analyte sensor of claim 14, wherein the glucose-responsive enzyme is glucose oxidase or glucose dehydrogenase. ### Claim 16 (depends on 15) The analyte sensor of claim 15, wherein the at least two enzymes comprise β-hydroxybutyrate dehydrogenase and a nicotinamide adenine dinucleotide oxidase. ### Claim 17 (depends on 16) The analyte sensor of claim 16, wherein the ketones-responsive active area comprises a first electron transfer agent and the glucose-responsive active area comprises a second electron transfer agent. ### Claim 18 (depends on 17) The analyte sensor of claim 17, wherein the first electron-transfer agent in the glucose-responsive active area and the second electron-transfer agent in the ketones-responsive active area are the same. ### Claim 19 (depends on 14) The sensor of claim 14, wherein the ketones-responsive active area is disposed closer to a distal end of the sensor than the glucose-responsive active area. ### Claim 20 (depends on 14) The analyte sensor of claim 14, wherein the multi-component mass transport limiting membrane comprises a first membrane for limiting inward diffusion of ketones to the ketones-responsive active area. ### Claim 21 (depends on 20) The analyte sensor of claim 20, wherein the multi-component mass transport limiting membrane further comprises a second membrane for limiting diffusion of glucose to the glucose-responsive active area disposed over the first membrane. ### Claim 22 (depends on 21) The analyte sensor of claim 21, wherein the second membrane is disposed over the glucose-responsive active area. ### Claim 23 (depends on 21) The analyte sensor of claim 21, wherein the first membrane comprises polyvinylpyridine. ### Claim 24 (depends on 23) The sensor of claim 23, wherein the second membrane comprises polyvinylpyridine-co-styrene.