NAD(P)-Dependent Sensor Electrodes With Mediated Electron Transfer

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Solution Overview

Problem

Existing analyte sensors lack stability and sensitivity for measuring NAD(P)+-dependent analytes, such as glucose, alcohol, and β-hydroxybutyrate, necessitating improved enzyme compositions and sensors for accurate and rapid analyte 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.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional enzyme compositions are used for analyte detection, then the sensor can measure analyte concentration, but the sensor lacks stability and sensitivity for accurate monitoring

Engineering Contradiction:
Improvesensor stabilityVSAvoidanalyte measurement accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent employs composite enzyme compositions containing multiple enzyme types (NAD(P)+-dependent dehydrogenase, NAD(P)H oxidoreductase) combined with synthetic polymers and transition metal complexes. This composite approach creates a synergistic system where the polymer matrix provides structural stability while the multi-enzyme system enhances measurement precision through coupled enzymatic reactions, resolving the contradiction between sensor stability and measurement accuracy.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent introduces NAD(P)+ as an intermediary molecule that mediates between the dehydrogenase and oxidoreductase enzymes. This intermediary enables efficient electron transfer and signal amplification, improving measurement sensitivity without compromising sensor stability. The transition metal complex serves as another intermediary to facilitate electron transfer to the electrode, enhancing both reliability and measurement precision.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If simple enzyme compositions are used, then the device complexity is low, but the sensitivity and accuracy for analyte measurement are insufficient

Engineering Contradiction:
Improveanalyte measurement accuracyVSAvoidenzyme composition complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple functional components into a single integrated enzyme composition system. The dehydrogenase, oxidoreductase, polymer, and transition metal complex are combined in one composition that can be applied directly to the electrode as a unified layer. This merging approach achieves high measurement precision through the synergistic interaction of components while avoiding the need for separate complex device structures.

Inventive Principle:
Principle #5Merging (Combining)

3Productivity

If rapid analyte monitoring is achieved, then the measurement speed is high, but the sensor stability over extended periods deteriorates

Engineering Contradiction:
Improvemeasurement speedVSAvoidsensor operational duration
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent utilizes parameter changes in the enzymatic reaction system to achieve rapid measurements while maintaining stability. The coupled enzyme reactions with NAD(P)+ cycling enable fast response times through efficient electron transfer kinetics. Meanwhile, the polymer matrix and crosslinking modify the physical parameters of the enzyme environment, providing structural stability that maintains sensor functionality over extended operational periods.

Inventive Principle:
Principle #35Parameter changes

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 rapid, clinically accurate, and stable electrochemical measurements of analytes, with linear signal output and sensitivity, suitable for in vivo monitoring over extended periods.

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 dehydrogenase

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:

Implementation Method 6

immobilized on electrodes using polymers and crosslinkers

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 7

two or more of these components may be bound or connected together

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentUS12577604B2NAD(P)-dependent responsive enzymes, electrodes and sensors, and methods for making and using the same
Publication Date: 2026.03.17 ABBOTT DIABETES CARE INC
  • US12577604B2 patent drawing
  • US12577604B2 patent drawing
  • US12577604B2 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.