NAD(P)- dependent responsive enzymes, electrodes and sensors, and methods for making and using the same

Inventors

Ouyang, Tianmei • Feldman, Benjamin J.

Assignees

Abbott Diabetes Care Inc

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Publication Number

US-12686882-B2

Patent

Publication Date

2026-07-21

Expiration Date


Abstract

NADP-dependent oxidoreductase compositions, and electrodes, sensors and systems that include the same. Analyte sensors include an electrode having a sensing layer disposed thereon, the sensing layer comprising a polymer and an enzyme composition distributed therein. The enzyme composition includes nicotinamide adenine dinucleotide phosphate (NAD(P)+) or derivative thereof; an NAD(P)+-dependent dehydrogenase; an NAD(P)H oxidoreductase; and an electron transfer agent comprising a transition metal complex.

Core Innovation

The disclosed invention relates to NAD(P)+-based electrochemical analyte sensors that include an inserted portion positioned below a subject’s skin surface for partial insertion. The sensor includes a working electrode and an enzyme composition deposited on the working electrode surface, and the enzyme composition comprises NAD(P)+ or a derivative, D-3-hydroxybutyrate dehydrogenase, diaphorase, and a polymeric redox mediator.

A key feature is that the NAD(P)+ is not covalently bonded to the polymeric redox mediator while still being incorporated into the enzyme composition on the electrode. The enzyme system is covered by a mass transport limiting membrane that limits flux of β-hydroxybutyrate to the working electrode.

The disclosed sensor architecture further includes a non-conductive material layer with a conductive layer forming the working electrode, and additional conductive layers may be provided for electrochemical functionality. The mass transport limiting membrane is disposed over the enzyme system to control analyte transport to the working electrode.

Claims Coverage

The document provides one independent claim describing an electrochemical analyte sensor with partial insertion below a subject’s skin surface, where β-hydroxybutyrate detection is mediated by an NAD(P)+-based enzyme system and a polymeric redox mediator under a mass transport limiting membrane. Five inventive features are identified in the independent claim.

Partially inserted electrochemical analyte sensor for below-skin detection

An electrochemical analyte sensor configured for partial insertion below a subject's skin surface, including a portion positioned above the subject's skin surface and an inserted portion positioned below the subject's skin surface.

Inserted working electrode with non-conductive layer and deposited NAD(P)+ enzyme system

The inserted portion comprises a non-conductive material layer, a first conductive layer on at least a portion of the non-conductive material with the first conductive layer being a working electrode, and an enzyme composition deposited on a surface of the first conductive layer.

NAD(P)+ enzyme composition with D-3-hydroxybutyrate dehydrogenase, diaphorase, and polymeric redox mediator

The enzyme composition comprises NAD(P)+ or derivative thereof, D-3-hydroxybutyrate dehydrogenase, diaphorase, and a polymeric redox mediator.

Mass transport limiting membrane that limits β-hydroxybutyrate flux to the working electrode

A mass transport limiting membrane disposed over the enzyme system to limit flux of β-hydroxybutyrate to the working electrode.

NAD(P)+ is not covalently bonded to the polymeric redox mediator

The NAD(P)+ is not covalently bonded to the polymeric redox mediator.

Overall, the claim coverage centers on an electrochemical analyte sensor configured for partial insertion below skin, with a working electrode carrying a deposited enzyme composition containing NAD(P)+, D-3-hydroxybutyrate dehydrogenase, and diaphorase, where a mass transport limiting membrane limits β-hydroxybutyrate flux to the working electrode.

Stated Advantages

Documented Applications

Not explicitly described in patent.

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