Multi-Mediator Reagent Formulation for Electrochemical Glucose Detection

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing glucose measurement technologies face challenges with mediator formulations in electrochemical sensors, including high background currents, poor stability, and limited sensitivity due to issues with osmium and ruthenium compounds, particularly when used in combination with flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH) and glucose oxidase (GOX).

Innovation Solution

A novel multi-mediator formulation combining ruthenium hexammine trichloride with specific osmium compounds, such as [Os(III)(bpy)2imCl]Cl2, which provides a synergistic effect, reducing background current and oxygen interference, and enhancing sensitivity and stability for glucose detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If high concentrations of osmium compounds (≥150 mM) are used as mediators, then sensitivity to glucose concentration is improved, but background current increases disruptively and stability in dry reagent deteriorates

Engineering Contradiction:
Improvesensitivity to glucose concentrationVSAvoidbackground current
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent combines multiple mediators (osmium compound and ruthenium compound) in specific ratios to achieve synergistic effects. This merging allows the system to maintain high sensitivity while reducing background current, as each mediator compensates for the limitations of the other when used alone at optimal concentrations.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent changes the concentration parameters of individual mediators from high single-mediator concentrations to lower multi-mediator concentrations. Specifically, it uses osmium compound at 1-50 mM and ruthenium compound at 100-200 mM, which collectively provide the sensitivity of high concentrations without the disruptive background current.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If ruthenium hexammine trichloride is used as mediator, then stability in dry reagent is improved, but mediation kinetics with FAD-GDH deteriorates to extremely slow rates

Engineering Contradiction:
Improvestability in dry reagentVSAvoidmediation kinetics
Core Design Contradiction:
Stability of the object's compositionVSSpeed

Solution Approach 1:

The patent merges ruthenium hexammine trichloride (providing stability) with osmium compounds (providing fast kinetics) in a multi-mediator system. The ruthenium compound maintains stability during storage while the osmium compound ensures rapid electron transfer kinetics, achieving both properties simultaneously.

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If osmium compounds are used at high concentrations, then sensitivity is improved, but stability in dry reagent deteriorates

Engineering Contradiction:
ImprovesensitivityVSAvoidstability in dry reagent
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent combines osmium compounds (providing sensitivity) with ruthenium compounds (providing stability) in specific concentration ratios. This allows the system to achieve high sensitivity through the osmium compound while the ruthenium compound compensates for the poor dry reagent stability of the osmium compound alone.

Inventive Principle:
Principle #5Merging (Combining)

4Device complexity

If single mediator systems are used, then device complexity is reduced, but performance reliability deteriorates due to unpredictable and erratic results

Engineering Contradiction:
Improvemediator formulation complexityVSAvoidperformance consistency
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent merges multiple mediators into a unified multi-mediator formulation with specific concentration ranges. This combination provides consistent and reliable performance across different test conditions, eliminating the erratic results observed with single-mediator systems while maintaining manageable formulation complexity.

Inventive Principle:
Principle #5Merging (Combining)

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 combination of ruthenium hexammine trichloride and [Os(III)(bpy)2imCl]Cl2 results in significantly reduced background current and improved sensitivity, enabling accurate glucose measurement with minimal oxygen interference, surpassing the performance of individual mediators and prior art formulations.

Implementation Method 1

ruthenium hexammine with certain osmium compounds results in a synergistic effect, providing a multi-mediator formulation that overcomes the shortcomings of each individual mediator

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Data Source

PatentEP3303605B1Multi-mediator reagent formulations for use in electrochemical detection
Publication Date: 2024.04.03 OMNI BIOMEDICAL INC
  • EP3303605B1 patent drawingFigure 1
  • EP3303605B1 patent drawingFigure 2
  • EP3303605B1 patent drawingFigure 3

AI summary

The present disclosure provides, inter alia, mediator formulations for the measurement of an analyte comprising at least one ruthenium compound and at least one osmium compound. Also disclosed are reagent formulations for the measurement of an analyte comprising at least one ruthenium compound and at least one osmium compound. Also disclosed are methods and devices for the measurement of an analyte in a sample.