NAD(P)-Dependent Enzyme Compositions for Stable Electrochemical Sensors

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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 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:

Improveanalyte measurement accuracyVSAvoidsensor stability

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent employs a composite enzyme composition containing multiple enzymes (NAD(P)+-dependent dehydrogenase, NAD(P)H oxidoreductase, and catalase) working synergistically. This composite system improves measurement accuracy while maintaining stability, as each enzyme performs a specific function in the analytical pathway, collectively achieving reliable and precise analyte detection.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent introduces NAD(P)+ as an intermediary electron carrier that mediates between the dehydrogenase reaction and the electrochemical detection system. This intermediary enables efficient electron transfer, enhancing both the sensitivity and stability of the sensor by creating a well-defined electron transfer pathway.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If conventional enzyme compositions are used, then basic analyte detection is possible, but sensitivity for rapid and accurate measurement is insufficient

Engineering Contradiction:

Improveanalyte detection sensitivityVSAvoidmeasurement speed

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent ensures continuous enzyme activity by optimizing the composition to maintain stable NAD(P)+ regeneration through the oxidoreductase and catalase system. This continuous action allows for rapid, repeated measurements without loss of sensitivity, enabling both high detection sensitivity and fast measurement speed for clinical applications.

Inventive Principle:

Principle #20Continuity of useful action

3Duration of action of stationary object

If simple enzyme compositions are used, then device complexity is low, but the sensor cannot maintain sensitivity over extended monitoring periods

Engineering Contradiction:

Improvesensor monitoring durationVSAvoidenzyme composition complexity

Core Design Contradiction:

Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The patent divides the enzymatic reaction into distinct segments, each performed by a specific enzyme: dehydrogenase for substrate oxidation, oxidoreductase for NAD(P)H oxidation, and catalase for H2O2 decomposition. This segmentation allows each component to be optimized independently while working together to extend sensor lifespan and maintain sensitivity over extended monitoring periods.

Inventive Principle:

Principle #1Segmentation

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, demonstrating linear response to analyte concentration and maintaining sensitivity over time, suitable for in vivo monitoring.

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

clinically accurate electrochemical measurements of analytes

Methodology Applied

Scientific EffectElectrochemical measurement:

Data Source

PatentUS12385077B2NAD(P)-dependent responsive enzymes, electrodes and sensors, and methods for making and using the same

Publication Date: 2025.08.12 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.