NAD(P)-Dependent Enzyme Electrodes for Stable Analyte Sensing

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Solution Overview

Problem

Existing analyte sensors lack stability and sensitivity for accurately measuring NAD(P)+-dependent analytes such as glucose, alcohol, and 3-Hydroxybutyrate, necessitating improved enzyme compositions and sensor designs for clinical accuracy and extended monitoring.

Innovation Solution

Development of enzyme compositions comprising NAD(P)+, NAD(P)+-dependent dehydrogenases, NAD(P)H oxidoreductases, and electron transfer agents with transition metal complexes, immobilized on electrodes using polymers and crosslinkers, enabling clinically accurate electrochemical measurements of analytes within seconds and over extended periods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional enzyme compositions are used for analyte detection, then the sensor can measure analytes, but the stability and sensitivity are insufficient for accurate clinical measurements

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidsensor stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent employs composite materials by combining multiple enzyme components (NAD(P)+-dependent dehydrogenase, NAD(P)H oxidoreductase) with electron transfer agents (transition metal complexes) and immobilizing them on electrode surfaces using polymers and crosslinkers. This composite structure enhances both the stability and sensitivity of the sensor system, resolving the contradiction between measurement precision and reliability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent introduces electron transfer agents with transition metal complexes as intermediaries between the enzyme reactions and the electrode. These mediators facilitate efficient electron transfer, improving both the sensitivity (measurement precision) and stability (reliability) of the electrochemical sensor system.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If existing sensor designs are used, then basic analyte detection is possible, but sensitivity for NAD(P)+-dependent analytes is insufficient

Engineering Contradiction:
Improvedetection sensitivityVSAvoidenzyme composition complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple functional components into a unified enzyme composition system where NAD(P)+-dependent dehydrogenase, NAD(P)H oxidoreductase, and electron transfer agents work synergistically. This combination enhances detection sensitivity for NAD(P)+-dependent analytes while managing complexity through integrated design.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The electron transfer agents with transition metal complexes serve as intermediaries that amplify the signal from enzyme-catalyzed reactions, significantly improving detection sensitivity without requiring overly complex device architecture.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If simple enzyme compositions are used, then the sensor design is straightforward, but the measurements lack clinical accuracy

Engineering Contradiction:
Improveclinical accuracyVSAvoidfabrication simplicity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-immobilizing the enzyme composition components on the electrode surface using polymers and crosslinkers before use. This pre-preparation step ensures clinical accuracy is achieved while simplifying the overall manufacturing process, as the complex enzyme system is prepared in advance rather than during final assembly.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The use of composite materials with polymers and crosslinkers provides a structured framework that facilitates manufacturing. The composite structure allows for systematic preparation and immobilization of enzyme components, making the fabrication process more manageable while achieving clinical accuracy.

Inventive Principle:
Principle #40Composite materials

4Duration of action of stationary object

If conventional sensors are used for extended monitoring, then short-term measurements are possible, but stability over extended periods is insufficient

Engineering Contradiction:
Improvemonitoring durationVSAvoidsignal stability
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent ensures continuity of useful action by immobilizing the enzyme composition on the electrode surface, allowing sustained catalytic activity over extended periods. The polymer and crosslinker matrix maintains continuous enzyme function, enabling long-term monitoring with stable signals.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The composite material structure with polymers and crosslinkers provides a stable matrix that maintains enzyme activity and signal reliability over extended monitoring periods, resolving the contradiction between duration and reliability.

Inventive Principle:
Principle #40Composite materials

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The enzyme compositions provide clinically accurate, rapid, and stable electrochemical measurements of analytes, with linear signal response to concentration changes, suitable for in vivo monitoring of glucose, alcohol, and 3-Hydroxybutyrate, meeting clinical accuracy standards.

Implementation Method 1

NAD(P)+-dependent dehydrogenases oxidize various biological molecules such as glucose, alcohol, and 3-Hydroxybutyrate

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

glucose can be oxidized by NAD-dependent glucose dehydrogenase, alcohol can be oxidized by NAD-dependent alcohol dehydrogenase

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 3

an NAD(P)+-dependent dehydrogenase, an NAD(P)H oxidoreductase and an electron transfer agent having a transition metal complex

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 4

electron transfer agent having a transition metal complex

Methodology Applied
Scientific EffectElectron transfer: Electrochemiluminescence

Implementation Method 5

one or more of the nicotinamide adenine dinucleotide phosphate (NAD(P)+) or derivative thereof, NAD(P)+-dependent dehydrogenase, NAD(P)H oxidoreductase and redox mediator are immobilized on the surface by the polymer

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS12577603B2NAD(P)-dependent responsive enzymes, electrodes and sensors, and methods for making and using the same
Publication Date: 2026.03.17 ABBOTT DIABETES CARE INC
  • US12577603B2 patent drawing
  • US12577603B2 patent drawing
  • US12577603B2 patent drawing

AI summary

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.