Biosensor Reagent Layer Stability and Hematocrit Bias

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Solution Overview

Problem

Conventional biosensors face issues with long-term stability and accuracy due to reagent degradation and the hematocrit effect, which leads to measurement drift and bias in glucose concentration readings, especially when stored and transported.

Innovation Solution

The electrochemical sensor strip design includes a reagent layer with reduced mediator and enzyme deposition densities, combined with a gated amperometric pulse sequence, to enhance stability and reduce hematocrit bias, achieving improved measurement performance and longer shelf-life.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional reagent compositions with substantial excess of enzyme and mediator are used, then long-term stability is improved, but measurement precision deteriorates due to drift in accuracy and precision over time

Engineering Contradiction:
Improvelong-term stabilityVSAvoidmeasurement accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent changes the concentration parameters of the reagent composition by using stoichiometric amounts of enzyme and mediator rather than substantial excess. This parameter change resolves the contradiction by achieving both long-term stability and measurement precision through optimized reagent ratios that prevent degradation drift while maintaining accurate measurements.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies partial action by using only the necessary stoichiometric amounts of reagents rather than excessive amounts. This resolves the contradiction by eliminating the harmful effects of excess reagent degradation while maintaining sufficient reagent activity for accurate long-term measurements.

Inventive Principle:
Principle #16Partial or excessive action

2Reliability

If substantial excess of enzyme and mediator are included in reagent composition, then long-term stability is improved, but device complexity increases due to larger sample volume requirements and longer analysis time

Engineering Contradiction:
Improvelong-term stabilityVSAvoidsample volume requirement
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the reagent composition parameters to use stoichiometric amounts, which reduces the required sample volume and simplifies the device design. This resolves the contradiction by eliminating the need for large sample volumes and complex timing protocols while maintaining long-term stability.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If conventional reagent compositions are used, then manufacturing precision is maintained, but measurement precision deteriorates due to hematocrit effect causing measurement bias

Engineering Contradiction:
Improvereagent composition consistencyVSAvoidglucose concentration accuracy
Core Design Contradiction:
Manufacturing precisionVSMeasurement precision

Solution Approach 1:

The patent changes the reagent composition parameters to stoichiometric ratios of enzyme to mediator, which eliminates the hematocrit effect and its associated measurement bias. This resolves the contradiction by maintaining manufacturing precision while achieving accurate glucose measurements across varying hematocrit levels.

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 solution results in a stability bias of less than ±10% and hematocrit bias of less than ±5% for whole blood samples with varying hematocrit levels, improving the accuracy and precision of glucose concentration measurements.

Implementation Method 1

The reagent layer includes a mediator and an enzyme system, where the mediator transfers electrons between the enzyme system and the conductor

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 2

The reagent layer includes a mediator and an enzyme system, where the mediator transfers electrons between the enzyme system and the conductor

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP3543348B1Biosensor system having enhanced stability and hematocrit performance
Publication Date: 2020.11.18 ASCENSIA DIABETES CARE HLDG AG
  • EP3543348B1 patent drawingFigure 1A~2A
  • EP3543348B1 patent drawingFigure 2B~2C
  • EP3543348B1 patent drawingFigure 3

AI summary

The present invention relates to electrochemical sensor strips and methods of determining the concentration of an analyte in a sample or improving the performance of a concentration determination. The electrochemical sensor strips may include at most 8 µg/mm2 of a mediator. The strips, the strip reagent layer, or the methods may provide for the determination of a concentration value having at least one of a stability bias of less than ±10% after storage at 50° C for 4 weeks when compared to a comparison strip stored at -20° C for 4 weeks, a hematocrit bias of less than ±10% for whole blood samples including from 20 to 60% hematocrit, and an intercept to slope ratio of at most 20 mg/dL. A method of increasing the performance of a quantitative analyte determination also is provided.