NAD(P) depot for NAD(P)-dependent enzyme-based sensors
Inventors
Ouyang, Tianmei • Fox, Cade • Liu, Zenghe • Oja, Stephen • Feldman, Benjamin J.
Assignees
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Publication Number
US-12404535-B2
Publication Date
2025-09-02
Expiration Date
Abstract
The present disclosure provides analyte sensors including one or more NAD(P)-dependent enzymes and an internal supply of NAD(P) for the detection of an analyte. The present disclosure further provides methods of using such analyte sensors for detecting one or more analytes present in a biological sample of a subject, and methods of manufacturing said analyte sensors.
Core Innovation
The invention relates to an analyte sensor that includes an internal supply of NAD(P) overcoated by a permeable polymer so that cofactor availability is maintained over time. This provides sustained, tunable NAD(P) release from an internal NAD(P) depot and addresses limited or poor diffusion of exogenous NAD(P).
The sensor further includes a permeable first working electrode disposed upon the active surface of the permeable polymer. An analyte-responsive active area is disposed upon a surface of the permeable working electrode and comprises an NAD(P)-dependent enzyme, including NAD(P)-dependent dehydrogenases, so that released NAD(P) supports the enzymatic reaction used to generate an analyte-dependent signal.
A mass transport limiting membrane overcoats the analyte-responsive area and is permeable to the analyte. The permeable membrane and associated permeable layers modulate analyte flux and support sensor response, including sustained output when the internal NAD(P) depot is present versus reduced output in controls lacking the depot. Optional diaphorase and a redox mediator are also described in connection with the analyte-responsive active area.
Claims Coverage
The independent claim set centers on an analyte sensor with five core inventive features: an internal supply of NAD(P), a permeable polymer overcoating that supply, a permeable first working electrode, an analyte-responsive area with an NAD(P)-dependent enzyme, and a mass transport limiting membrane permeable to the analyte. Dependent claims further specify enzyme class, materials, and optional active-area components.
Internal supply of NAD(P)
An internal supply of NAD(P).
Permeable polymer overcoating the internal supply of NAD(P)
A permeable polymer that overcoats the internal supply of NAD(P).
Permeable first working electrode disposed upon the active surface
A first working electrode disposed upon the active surface of the permeable polymer, wherein the first working electrode is a permeable working electrode.
NAD(P)-dependent enzyme analyte-responsive active area
An analyte-responsive active area disposed upon a surface of the first working electrode, wherein the analyte-responsive area comprises an NAD(P)-dependent enzyme.
Mass transport limiting analyte-permeable membrane overcoating the active area
A mass transport limiting membrane that overcoats the analyte-responsive area, wherein the membrane is permeable to the analyte.
NAD(P)-dependent dehydrogenase analyte-responsive enzyme
The analyte-responsive area comprises an NAD(P)-dependent dehydrogenase as the NAD(P)-dependent enzyme.
Polyether-based permeable polymer
The permeable polymer includes a polyether-based polymer.
Carbon nanotube permeable working electrode
The permeable working electrode includes a carbon nanotube.
Diaphorase in the analyte-responsive active area
The analyte-responsive active area includes diaphorase.
Overall, the claim coverage is directed to maintaining NAD(P) availability using an internal NAD(P) supply overcoated by a permeable polymer, combined with an NAD(P)-dependent enzyme active area on a permeable working electrode and an analyte-permeable mass transport limiting membrane. Dependent claims narrow the sensor to dehydrogenases, polyether-based polymers, carbon nanotube permeable electrodes, and optional diaphorase and redox mediator features.
Stated Advantages
Sustained signal is produced when an internal NAD(P) depot is present, versus reduced signal in controls lacking the depot.
Addresses limited or poor diffusion of exogenous NAD(P) by providing an internal NAD(P) depot for NAD(P)-dependent enzymatic sensing.
Documented Applications
In vivo analyte monitoring, including detection in dermal/interstitial fluid contexts.
Monitoring for ketones.
Detection/monitoring of analytes including glucose, lactate, and alcohols such as ethanol.
Multi-analyte and multi-electrode sensor configurations with differentiated active areas and membrane overcoating portions.
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