Biosensor Electrode Area Adjustment for Dose-Response Consistency

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Solution Overview

Problem

Existing electrochemical biosensors face inaccuracies in analyte concentration measurement due to variations in the diffusion coefficient and system-specific coefficients during production, leading to inconsistent dose-response curves, which require complex calibration methods and result in waste and increased production costs.

Innovation Solution

The method involves producing biosensors with adjustable electrical patterns, specifically the working electrode's effective area, which is determined and adjusted during production to maintain the dose-response curve within a predetermined range, eliminating the need for post-production calibration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If biosensors are produced using standard manufacturing processes, then production efficiency and output are improved, but variations in diffusion coefficient and system-specific coefficients occur leading to inconsistent dose-response curves

Engineering Contradiction:
Improveproduction efficiencyVSAvoiddose-response curve consistency
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by adjusting the effective area of the working electrode based on measured dose-response characteristics. During production, the effective area is varied (e.g., between 0.3mm² to 0.5mm²) to compensate for variations in diffusion coefficient and system-specific coefficients, thereby maintaining consistent dose-response curves across different production batches while preserving high production efficiency.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If complex calibration methods are used to correct dose-response variations, then measurement precision is improved, but device complexity and user operation difficulty increase

Engineering Contradiction:
Improveanalyte concentration measurement accuracyVSAvoidcalibration system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent implements preliminary action by pre-adjusting the effective area of the working electrode during manufacturing to achieve consistent dose-response curves. This eliminates the need for complex post-production calibration procedures, as the biosensors are already optimized for accurate analyte concentration measurement upon delivery to the user.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies self-service by enabling the biosensor to self-correct for manufacturing variations through its design. The effective area is determined based on dose-response measurements, allowing the sensor to automatically compensate for variations without requiring external calibration equipment or user intervention.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If multiple correction coefficients are provided for different production batches, then measurement precision is improved, but loss of time and increased production costs occur

Engineering Contradiction:
Improveanalyte concentration estimation accuracyVSAvoidcalibration time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent varies the effective area parameter of the working electrode to compensate for batch-to-batch variations in diffusion coefficient and system-specific coefficients. This single parameter adjustment replaces the need for multiple correction coefficients, eliminating calibration time for users while maintaining measurement precision across different production batches.

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

This approach ensures consistent analyte concentration measurements across batches without the need for user calibration or multiple correction coefficients, reducing waste and production costs by maintaining dose-response curves within a desired tolerance.

Implementation Method 1

The response of an electrochemical biosensor to a potential step is largely governed by the Cottrell equation (F. G. Cottrell, Z. Physik. Chem., (1902)), Equation (1), below. where n - number of electrons per molecule of analyte F - Faraday Constant A - working electrode area D - diffusion coefficient t - time after application of potential step C - Analyte concentration

Methodology Applied
Scientific EffectCottrell equation (diffusion-controlled current): Diffusion

Implementation Method 2

A chemical process takes place when a liquid sample such as blood containing the analyte of interest hydrates the film. During this process, the film swells, analyte molecules diffuse into the film

Methodology Applied
Scientific EffectHydration and swelling: Absorption (physical)

Implementation Method 3

analyte molecules diffuse into the film, and, with the aid of the analyte-specific enzymes present in the film, electron(s) are exchanged with the mediator molecules

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 4

with the aid of the analyte-specific enzymes present in the film, electron(s) are exchanged with the mediator molecules

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Implementation Method 5

electron(s) are exchanged with the mediator molecules. In the presence of a specifically applied or controlled electrical potential, the mediator molecules diffuse to the electrode surface and are reduced or oxidized

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 6

In the presence of a specifically applied or controlled electrical potential, the mediator molecules diffuse to the electrode surface and are reduced or oxidized

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 7

Resulting current is then measured and then correlated using known techniques (e.g. amperometry, coulometry, potentiometry, voltammetry) to an amount, concentration or other desired characteristic of the analyte

Methodology Applied
Scientific EffectAmperometry:

Data Source

PatentEP2594939B1method of manufacturing of a biosensor with predetermined dose response curve
Publication Date: 2020.12.02 ROCHE DIABETES CARE GMBH
  • EP2594939B1 patent drawingFigure 1A
  • EP2594939B1 patent drawingFigure 1B
  • EP2594939B1 patent drawingFigure 2

AI summary

The present invention provides a system of biosensors whose dose-response curves are maintained within a predetermined and desired range or tolerance during production by selecting a feature of the biosensors that can be varied during production. For example, in one exemplary embodiment the effective area of the working electrode of an electrochemical biosensor can be varied during production as needed to offset variations that occur, e.g., in the reagent of the biosensors as production proceeds.