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-12649944-B2
Publication Date
2026-06-09
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 electrochemical analyte sensor having a working electrode with a lactate-responsive active area disposed on the working electrode. The lactate-responsive active area comprises nicotinamide adenine dinucleotide (phosphate) (NAD(P)), lactate dehydrogenase, diaphorase, an electron transfer agent comprising a transition metal complex, together with a polymer, and the sensor includes an internal supply of NAD(P).
A mass transport limiting membrane permeable to lactate overcoats the lactate-responsive area, so lactate reaches the lactate-responsive region while interferents are restricted. The document also describes an interference domain as a molecular sieve restricting interferents, including layered architectures where the interference domain and the mass-transport-limiting permeable membrane overcoat the electroactive surface.
The invention further describes layered and configurable electrode architectures, including arrangements for counter/reference/working electrode placement and permeable electrode geometries such as permeable wire electrode/tail geometries. An internal NAD(P) depot concept is also described with permeable overcoatings to control cofactor diffusion and sustained release, including designs that support NAD(P)-dependent dehydrogenases/diaphorase systems and electron transfer/redox mediators using transition metal complexes optionally associated with polymeric backbones for stable operation.
Claims Coverage
Independent claim clm-00001 defines an analyte sensor for lactate detection with a lactate-responsive active area plus internal NAD(P) and a lactate-permeable mass transport limiting membrane. Three inventive features are identified in the independent claim, and the dependent claims refine the sensor by specifying additional structural and material features and, in one dependent member, an assay workflow for determining lactate concentration from an electrochemical signal.
Lactate-responsive electroactive area with NAD(P) and catalytic components
A lactate-responsive active area disposed on a working electrode, the lactate-responsive active area comprising NAD(P), lactate dehydrogenase, diaphorase, an electron transfer agent comprising a transition metal complex, and a polymer.
Internal NAD(P) supply
An internal supply of NAD(P).
Mass transport limiting permeable membrane overcoating the lactate-responsive area
A mass transport limiting membrane permeable to lactate that overcoats the lactate-responsive area.
Across the dependent members referenced, the claims further specify permeable polymer overcoatings, permeable working electrode materials including carbon nanotube, covalent bonding of lactate dehydrogenase to the polymer, and additional active area responsiveness for glucose, ketone, or alcohol. One dependent member further defines determining lactate concentration from a signal obtained under an applied potential at or above a lactate-responsive oxidation-reduction potential.
Stated Advantages
Provides sustained detection by using an internal NAD(P) supply to overcome insufficient or diffusion-limited exogenous cofactor availability.
Enables electrochemical detection by releasing NAD(P) over time through a permeable polymer layer so that the signal can be obtained at or above an oxidation-reduction potential proportional to analyte concentration.
Documented Applications
In vivo analyte monitoring using a lactate sensor by obtaining an electrochemical signal at or above an oxidation-reduction potential and determining lactate concentration from that signal.
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