Implantable Micro-Biosensor Electrode Regeneration for Stable Glucose Sensing

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Solution Overview

Problem

Existing implantable continuous glucose monitoring systems face challenges in accurately measuring glucose concentrations due to interference from substances like ascorbic acid, acetaminophen, uric acid, and protein, and have limited service life due to silver/silver chloride electrode consumption, leading to instability and increased wound size during implantation.

Innovation Solution

An implantable micro-biosensor design featuring multiple electrodes and a chemical reagent layer that uses distinct potential differences to measure glucose, eliminate interference, and regenerate silver halide, allowing for accurate and extended monitoring with reduced electrode consumption and improved implantation characteristics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a polymer membrane is used to filter out interfering substances, then measurement accuracy is improved, but it remains difficult to filter out the interfering substances completely

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidcomplete filtration effectiveness
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent segments the filtration function into multiple specialized membranes: a first selective membrane for ascorbic acid and a second selective membrane for acetaminophen. This segmentation allows each membrane to target specific interfering substances, achieving more complete filtration than a single general-purpose membrane could provide.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces enzyme layers as intermediary components between the electrodes and the biological fluid. Glucose oxidase and other enzymes are immobilized on the electrode surfaces, serving as mediators that catalyze specific reactions while preventing direct contact between interfering substances and the electrodes, thereby improving measurement accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If multiple working electrodes with different enzymes are used to read multiple signals, then measurement accuracy is improved, but the process becomes very complicated

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple electrode functions into a single integrated electrode structure. The electrode is equipped with multiple enzyme layers (glucose oxidase, uric acid oxidase, etc.) that can simultaneously or sequentially detect different analytes, eliminating the need for separate electrodes for each measurement and simplifying the overall system.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The electrode design achieves multi-functionality by incorporating multiple enzyme layers that can detect various analytes including glucose, uric acid, and other substances. This universal electrode can perform multiple measurement functions without requiring separate specialized electrodes for each analyte.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If silver/silver chloride is used as the counter electrode material, then stable sensing potentials are obtained, but silver chloride is dissolved resulting in loss of chloride ions and shift of reference potential

Engineering Contradiction:
Improvesensing potential stabilityVSAvoidservice life
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent implements a regeneration mechanism for the silver/silver chloride counter electrode. By applying a reverse voltage or chemical treatment periodically, the consumed silver chloride is regenerated from the silver and chloride ions in the electrolyte, thereby recovering the electrode material and extending the device service life while maintaining potential stability.

Inventive Principle:
Principle #34Discarding and recovering

Solution Approach 2:

The counter electrode system is designed to self-regenerate through electrochemical reactions. The silver chloride that dissolves during operation can be reprecipitated and regenerated in situ by controlling the electrode potential, allowing the electrode to restore its own functionality without external intervention and maintain stable sensing potentials throughout the device lifetime.

Inventive Principle:
Principle #25Self-service

4Duration of action of stationary object

If the counter electrode length is increased to greater than 10 mm to extend service life, then electrode consumption is reduced, but the biosensor needs to be implanted at an oblique angle resulting in larger wound and higher infection risk

Engineering Contradiction:
Improveservice lifeVSAvoidinfection risk and wound size
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the electrode geometry parameters by increasing the width or surface area of the counter electrode rather than its length. This parameter substitution allows achieving the required electrode consumption rate and service life without extending the implantation depth, enabling perpendicular implantation and reducing wound size and infection risk.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Instead of extending the electrode in the longitudinal dimension (length > 10 mm), the patent compensates for consumption by increasing the transverse dimension (width or surface area). This dimensional substitution maintains adequate service life while allowing shallow perpendicular implantation, avoiding the need for oblique angle insertion and associated complications.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 micro-biosensor achieves accurate glucose monitoring with reduced interference and extended service life, minimizing wound size and infection risk during implantation, while maintaining measurement stability and accuracy over time.

Implementation Method 1

glucose is subjected to a catalysis reaction with glucose oxidase (GOx) to produce gluconolactone and a reduced glucose oxidase, followed by an electron transfer reaction between the reduced glucose oxidase and oxygen in a biological fluid of the body to produce hydrogen peroxide (H2O2) as a byproduct

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

The biosensor measures a physiological signal in response to a glucose concentration in the body, and the measurement thereof is mostly based on an electrochemical process

Methodology Applied
Scientific EffectElectrochemical process:

Implementation Method 3

silver chloride would be dissolved, resulting in the loss of chloride ions, which will cause a shift of the reference potential. When the silver/silver chloride is used for the counter electrode so as to be actually involved in a redox reaction, silver chloride would be even more consumed by reduction of silver chloride to silver

Methodology Applied
Scientific EffectReduction: Reduction

Data Source

PatentEP3771414B1Operation procedure of an implantable micro-biosensor
Publication Date: 2024.07.10 BIONIME
  • EP3771414B1 patent drawingFigure 1
  • EP3771414B1 patent drawingFigure 2~4
  • EP3771414B1 patent drawingFigure 5

AI summary

An implantable micro-biosensor includes at least one counter electrode (4), a first working electrode (2), a chemical reagent layer (6), and at least one second working electrode (3). The chemical reagent layer (6) reacts with an analyte to product a product, such that a first sensing section (20) of the first working electrode (2) is driven to perform a measurement action. A second sensing section (30) of the second working electrode (3) is driven to perform an interference-eliminating action to consume interference. The second working electrode (3) cooperates with the counter electrode (4) to permit the counter electrode (4) to be driven to perform a regeneration action to regenerate silver halide.