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Publication Number
US-10627361-B2
Publication Date
2020-04-21
Expiration Date
Abstract
An electrochemical test device for determining a concentration of an analyte in a fluid sample is provided. The electrochemical test device comprises a set of electrodes including a working electrode for the analyte and sensing chemistry for the working electrode, wherein the sensing chemistry comprises a diaphorase, an electron transfer agent having a standard redox potential in the range of −0.52 to 0.18 V, an NAD(P)+-dependent dehydrogenase and a cofactor for the NAD(P)+-dependent dehydrogenase.
Core Innovation
An electrochemical test device determines a concentration of an analyte in a fluid sample using a set of electrodes including a working electrode and sensing chemistry disposed in layers on the working electrode. The sensing chemistry comprises a diaphorase, an electron transfer agent having a standard redox potential in the range of −0.52 to 0.18 V, and an NAD(P)+-dependent dehydrogenase with a cofactor for the NAD(P)+-dependent dehydrogenase.
The layers include a layer that is not adjacent the working electrode, and the layer that is not adjacent the working electrode comprises the NAD(P)+-dependent dehydrogenase. The cofactor for the NAD(P)+-dependent dehydrogenase is restricted so that only the layer not adjacent the working electrode comprises the cofactor, while the remaining layers are defined by their adjacency relationships.
The disclosed layered sensing chemistry reduces NAD(P)+/NAD(P)H oxidation overpotential and reduces background noise and interference, including uric acid, to provide improved sensitivity with low detection and faster response in a short time window. Example layer configurations are described in connection with analyte targets, including glycerol with glycerol dehydrogenase, β-hydroxybutyrate with β-hydroxybutyrate dehydrogenase, and glucose with NAD+-glucose dehydrogenase.
Representative electron transfer agents and optional reagent components are described, including ruthenium hexaammine trichloride, ruthenium pentaammine chloride, and osmium phendione, and optional components such as FMN, phosphate/Tris buffer, and hydroxyethyl cellulose. The document further describes exemplary apparatus and meter circuitry together with test-strip electrode and layer construction and materials for the electrochemical test device.
Claims Coverage
The document identifies one independent claim defining a layered electrochemical test device, with inventive features centered on the combination of diaphorase, an electron transfer agent with a specified standard redox potential range, and an NAD(P)+-dependent dehydrogenase with a cofactor, together with the constrained layer placement where the NAD(P)+-dependent dehydrogenase and only the cofactor are contained in a layer not adjacent the working electrode. Dependent claims refine the electron transfer agent, constrain metal oxidation state and structure, and narrow the analyte via specific NAD(P)+-dependent dehydrogenases and placement relationships.
Layered sensing chemistry on the working electrode with constrained cofactors
An electrochemical test device having sensing chemistry disposed on the working electrode in layers that comprises a diaphorase, an electron transfer agent having a standard redox potential in the range of −0.52 to 0.18 V, an NAD(P)+-dependent dehydrogenase and a cofactor for the NAD(P)+-dependent dehydrogenase, where a layer not adjacent the working electrode comprises the NAD(P)+-dependent dehydrogenase and only the layer not adjacent the working electrode comprises the cofactor.
Electron transfer agent with ruthenium or osmium complex character
The electrochemical test device wherein the electron transfer agent is a ruthenium- or osmium-based electron transfer agent.
Electron transfer agent defined by Formula I with constrained integers
The electrochemical test device wherein the ruthenium- or osmium-based electron transfer agent is a complex of formula I with each B and integer constraints where x is an integer selected from 1 to 5, y is an integer selected from 1 to 5, x+y is 6 or 8, n is an integer selected from 1 to 6, and X is any suitable counterion.
Electron transfer agent metal oxidation state constrained to 2+ or 3+
The electrochemical test device wherein the metal oxidation state is selected to be either 2+ or 3+.
Glucose determination using NAD+-glucose dehydrogenase
The electrochemical test device configured to determine the concentration of glucose using NAD(P)+-dependent dehydrogenase that is NAD+-glucose dehydrogenase.
Diaphorase located in the layer adjacent the working electrode
The electrochemical test device configured so that a layer adjacent the working electrode includes diaphorase, and wherein the layer adjacent the working electrode optionally includes an electron transfer agent.
Overall claim coverage centers on layered sensing chemistry on a working electrode that uses diaphorase, an electron transfer agent with a standard redox potential range, and an NAD(P)+-dependent dehydrogenase while restricting the NAD(P)+ cofactor to only a non-adjacent layer, with dependent refinements covering ruthenium/osmium electron transfer agents, Formula I constraints, metal oxidation state, glucose-specific dehydrogenase selection, and diaphorase placement in the adjacent layer.
Stated Advantages
Reducing NAD(P)+/NAD(P)H oxidation overpotential.
Reducing background noise and interference, including uric acid.
Improved sensitivity with low detection.
Faster response in a short time window.
Documented Applications
Electrochemical determination of analyte concentrations in fluid samples using the electrochemical test device.
Glycerol measurement using glycerol dehydrogenase.
β-Hydroxybutyrate measurement using β-hydroxybutyrate dehydrogenase.
Glucose measurement using NAD+-glucose dehydrogenase.
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