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 β-hydroxybutyrate, necessitating improved sensor technologies for clinical accuracy and extended monitoring.

Innovation Solution

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 analyte sensors are used, then basic analyte detection is possible, but stability and sensitivity are insufficient for accurate measurement of NAD(P)+-dependent analytes

Engineering Contradiction:

Improvemeasurement accuracyVSAvoidsensor stability

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent employs a composite enzyme system comprising NAD(P)+-dependent dehydrogenase, NAD(P)H oxidoreductase, and electron transfer agents with transition metal complexes. This multi-enzyme composite architecture enables efficient electron transfer cascades while maintaining high stability and sensitivity for analyte detection, directly resolving the contradiction between measurement precision and sensor reliability.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent introduces electron transfer agents containing transition metal complexes as intermediary components between the dehydrogenase and oxidoreductase enzymes. These mediators facilitate efficient electron transfer, enhancing both the sensitivity and stability of the sensor system while enabling accurate measurement of NAD(P)+-dependent analytes.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of stationary object

If enzyme compositions are immobilized on electrodes using polymers and crosslinkers, then extended monitoring is enabled, but device complexity increases

Engineering Contradiction:

Improvemonitoring durationVSAvoidsensor structure complexity

Core Design Contradiction:

Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The patent combines multiple functional components (enzymes, electron transfer agents, polymers, and crosslinkers) into an integrated enzyme composition that is co-immobilized on the electrode surface. This merging of components simplifies the overall device structure while enabling extended monitoring duration through stable, long-lasting enzyme activity.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The polymer matrix serves multiple functions simultaneously: it provides structural support for enzyme immobilization, facilitates electron transfer, maintains enzyme stability, and enables extended operational duration. This multi-functionality reduces the need for additional specialized components, thereby limiting the increase in device complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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, stable, and sensitive electrochemical measurements of analytes, with linear signal response to analyte concentration, suitable for in vivo monitoring of glucose, alcohol, and β-hydroxybutyrate.

Implementation Method 1

glucose can be oxidized by NAD-dependent glucose dehydrogenase, alcohol can be oxidized by NAD-dependent alcohol dehydrogenase, β-Hydroxybutyrate can be oxidized by NAD-dependent D-3-Hydroxybutyrate dehydrogenase

Methodology Applied

Scientific EffectOxidation: Oxidation

Implementation Method 2

NAD(P)+-dependent dehydrogenases

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 3

NAD(P)H oxidoreductase

Methodology Applied

Scientific EffectRedox reactions: Redox Reactions

Implementation Method 4

electron transfer agent having a transition metal complex

Methodology Applied

Scientific EffectElectron transfer:

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

PatentUS20260002189A1NAD(p)- dependent responsive enzymes, electrodes and sensors, and methods for making and using the same

Publication Date: 2026.01.01 ABBOTT DIABETES CARE INC

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.