Biosensor AC Impedance Glucose Measurement

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Solution Overview

Problem

Conventional methods for measuring blood glucose concentrations, particularly using electrochemical techniques, face challenges such as interference from temperature, hematocrit, and other electrochemically active compounds, leading to inaccurate results and prolonged measurement times.

Innovation Solution

A method involving the application of low-amplitude AC waveforms to body fluid samples in a biosensor, using a mediator system to generate a linear faradic response, with high-frequency AC signals to detect hematocrit and temperature effects and low-frequency signals to measure glucose concentration, processed through an equivalent circuit model to provide accurate and rapid measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional electrochemical methods are used to measure glucose concentration, then the measurement can be performed, but the measurement time is prolonged and accuracy is reduced due to interference from temperature, hematocrit, and other factors

Engineering Contradiction:
Improveglucose concentration measurement accuracyVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the measurement process into two distinct phases: a steady-state DC measurement phase that captures glucose concentration information, and a transient AC measurement phase that captures interference information. This segmentation allows each measurement type to be optimized independently, resolving the contradiction between measurement speed and accuracy by collecting all necessary data more efficiently.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces AC impedance measurements as an intermediary technique to detect and quantify interference factors (temperature, hematocrit, electrode blockage) separately from the glucose measurement. This intermediary measurement enables correction of the DC glucose signal, improving accuracy without requiring prolonged measurement times.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If AC impedance measurements are applied sequentially with DC current to correct for interference factors, then measurement accuracy is improved, but the total measurement time is extended

Engineering Contradiction:
Improveglucose concentration measurement accuracyVSAvoidmeasurement throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent merges the DC and AC measurement processes by initiating AC impedance measurements during the transient phase before the DC current is fully applied. This overlapping of measurement phases allows interference correction data to be collected simultaneously with glucose concentration data, maintaining high accuracy while improving measurement throughput.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent performs preliminary AC impedance measurements during the transient phase before the steady-state DC measurement is complete. This preliminary action captures interference factor information early in the measurement sequence, allowing for faster processing and reducing the total time required to achieve accurate corrected glucose concentrations.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If constant potential is applied to initiate the electrochemical reaction, then glucose concentration can be measured, but interfering compounds generate additional DC current causing positive bias

Engineering Contradiction:
Improveglucose concentration measurement accuracyVSAvoidinterference from electrochemically active compounds
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent uses AC impedance measurements as an intermediary to detect the presence and magnitude of interference currents generated by electrochemically active compounds. By measuring the AC response separately from the DC glucose signal, the system can identify and correct for positive bias caused by interfering substances, improving measurement accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts interference information from the total current signal by applying AC impedance measurements that specifically probe the electrochemical cell's impedance characteristics. This extraction process separates the interference component from the glucose signal, allowing for correction of positive bias without affecting the glucose measurement itself.

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

This approach allows for accurate and rapid measurement of blood glucose concentrations, reducing measurement time and minimizing errors from interferents like hematocrit and temperature, thereby improving diabetic management and broader medical diagnostics.

Implementation Method 1

using a mediator system to generate a linear faradic response

Methodology Applied
Scientific EffectFaradic response:

Implementation Method 2

the application of an alternative potential of variable frequency and the measurement of cell impedance

Methodology Applied
Scientific EffectAC impedance: Electrical Impedance Tomography

Implementation Method 3

measuring the resulting charge or current proportional to the glucose concentration

Methodology Applied
Scientific EffectElectrochemical reaction:

Implementation Method 4

impediments of reactant diffusion to the electrode surface would also affect the resulting current

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP2521912B1Sample characterization based on ac measurement methods
Publication Date: 2016.10.12 F HOFFMANN LA ROCHE & CO AG
  • EP2521912B1 patent drawingFigure 1~12
  • EP2521912B1 patent drawingFigure 2a
  • EP2521912B1 patent drawingFigure 2b

AI summary

One aspect concerns a technique for detecting analyte concentrations, such as glucose concentrations, in blood or other bodily fluids. This technique utilizes an electrochemical test strip that includes a mediator system that generates a linear faradic response at relatively low applied potential differences. An alternating current excitation signal is applied to blood in the test strip. The alternating current excitation signal includes a low frequency signal and a high frequency signal that has a higher frequency than the low frequency signal. The glucose concentration is determined by measuring a low frequency response to the low frequency signal, measuring a high frequency response to the high frequency signal, estimating the glucose concentration based on the low frequency response, and correcting the glucose concentration for one or more error-causing variables based on the high frequency response.