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
Engineering 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
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.
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.
2Measurement precision
If simple enzyme compositions are used, then the device complexity is low, but the sensitivity and accuracy for analyte measurement are insufficient
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.
3Productivity
If rapid analyte monitoring is achieved, then the measurement speed is high, but the sensor stability over extended periods deteriorates
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.
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
Implementation Method 2
NAD(P)+-dependent dehydrogenase
Implementation Method 3
NAD(P)H oxidoreductase
Implementation Method 4
electron transfer agent having a transition metal complex
Implementation Method 5
clinically accurate electrochemical measurements of analytes
Implementation Method 6
immobilized on electrodes using polymers and crosslinkers
Implementation Method 7
two or more of these components may be bound or connected together
Data Source
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.


