Enzymatic Electrode with Covalent Nanoparticle Binding

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Solution Overview

Problem

Existing enzymatic non-fluidic sensors for glucose monitoring face inefficiencies due to spatial separation of hydrogen peroxide generation and decomposition, enzyme inactivation, sensor drift from hydrogel swelling, limited electron transfer with synthetic redox mediators, and complex manufacturing processes.

Innovation Solution

A conductive electrode with a conjugate of enzyme molecules and nanoparticles covalently bound to the surface via sulfur-containing functional groups, where the nanoparticles are not bound to the electrode, facilitating efficient hydrogen peroxide decomposition and reducing sensor drift and manufacturing complexity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If enzyme molecules are bound to conductive layers with spatial separation of H2O2 generation and decomposition sites, then the sensor can function for glucose monitoring, but the conversion rate of H2O2 at the working electrode becomes inefficient

Engineering Contradiction:
Improveconversion rate of H2O2VSAvoidspatial separation structure
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent combines the enzyme layer and conductive layer into a single integrated layer, eliminating the spatial separation between H2O2 generation and decomposition sites. This merging allows H2O2 to be immediately decomposed where it is generated, significantly improving conversion efficiency while simplifying the overall sensor structure.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If H2O2 is generated and decomposed at separated locations in the enzyme layer, then the sensor can operate, but extended presence of H2O2 inactivates enzyme molecules

Engineering Contradiction:
Improveenzyme activity stabilityVSAvoidenzyme layer structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

By merging the enzyme and conductive properties into a single layer, the patent ensures that H2O2 is decomposed immediately at the site of generation. This eliminates the extended presence of H2O2 that would otherwise diffuse through the enzyme layer and cause inactivation, thereby improving enzyme stability and sensor reliability.

Inventive Principle:
Principle #5Merging (Combining)

3Reliability

If hydrogel-encapsulated enzyme molecules are applied to electrode surface, then the enzyme is protected, but the gel swells in contact with aqueous media causing sensor drift

Engineering Contradiction:
Improvemeasurement signal stabilityVSAvoidhydrogel volume stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent extracts the hydrogel encapsulation component from the sensor design, replacing it with a conductive layer that directly binds enzyme molecules. This elimination of hydrogel removes the source of swelling and associated sensor drift, while maintaining enzyme protection and activity through direct covalent binding to the conductive surface.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If redox mediator and enzyme are covalently incorporated into polymeric structure to avoid sensor drift, then stability is improved, but electron transfer from enzyme to mediator becomes inefficient

Engineering Contradiction:
Improvesensor drift preventionVSAvoidelectron transfer efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent removes the synthetic redox mediator and polymeric structure from the sensor design. Instead, it uses a conductive layer that provides both structural stability and efficient electron transfer pathways. The direct electrical connection between enzyme active sites and the conductive surface enables efficient electron transfer without the mobility limitations imposed by polymeric structures.

Inventive Principle:
Principle #2Taking out (Extraction)

5Ease of manufacture

If paste-based enzyme layer with polymeric binder is applied to electrode surface, then the enzyme layer can be formed, but the layer is brittle and cannot be applied over larger areas on curved surfaces

Engineering Contradiction:
Improveenzyme layer applicationVSAvoidapplicability to curved surfaces
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent eliminates the polymeric binder from the enzyme layer formulation, replacing it with a conductive layer that forms a flexible, adherent coating. This conductive layer can be applied as a solution or dispersion that dries to form a crack-free coating on curved surfaces, overcoming the brittleness issue of paste-based formulations with polymeric binders.

Inventive Principle:
Principle #2Taking out (Extraction)

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 solution enables efficient and reproducible enzyme electrode manufacturing with improved glucose monitoring capabilities, reducing sensor drift and enhancing electron transfer efficiency without the need for synthetic redox mediators, while maintaining stability and applicability to curved surfaces.

Implementation Method 1

The enzyme molecules may catalyze a redox reaction, thereby generating an electrically detectable signal

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

The enzyme molecules may catalyze a redox reaction, thereby generating an electrically detectable signal

Methodology Applied
Scientific EffectRedox reaction: Redox Reactions

Implementation Method 3

the enzyme GOD (EC 1.1.3.4), which catalyzes the conversion of the analyte glucose to gluconolactone

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 4

the enzyme GOD (EC 1.1.3.4), which catalyzes the conversion of the analyte glucose to gluconolactone

Methodology Applied
Scientific EffectCatalysis: Catalysis

Implementation Method 5

The generated H2O2 may be catalytically decomposed to H2O, resulting in an electrical current which correlates to the glucose concentration

Methodology Applied
Scientific EffectCatalysis: Catalysis

Implementation Method 6

The generated H2O2 may be catalytically decomposed to H2O, resulting in an electrical current

Methodology Applied
Scientific EffectDecomposition: Decomposition (biological)

Implementation Method 7

a conjugate comprising at least one enzyme molecule is covalently bound to the conductive surface

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentEP3363910B1Continuous analyte monitoring electrode with crosslinked enzyme
Publication Date: 2023.12.06 ROCHE DIABETES CARE GMBH
  • EP3363910B1 patent drawingFigure 1
  • EP3363910B1 patent drawingFigure 2
  • EP3363910B1 patent drawingFigure 3

AI summary

The present invention relates to an enzymatic electrode comprising a conductive surface and wherein a conjugate comprising at least one enzyme molecule is covalently bound to the conductive surface. The electrode is suitable for continuous analyte monitoring, particularly for continuous glucose monitoring (CGM) with glucose oxidase (GOD) as enzyme molecule. Further, the invention relates to an electrochemical sensor for measuring the concentration of an analyte, e.g. glucose under in vivo conditions comprising the enzymatic electrode.