Electrochemical Sensor Pulse Sequences for Interference Compensation

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Solution Overview

Problem

Existing methods for measuring analyte concentrations in biological fluids, such as glucose in blood, face challenges due to variability in reaction rates and interference from substances like maltose and oxygen levels, leading to inaccurate results, especially in the presence of interfering compounds and varying conditions.

Innovation Solution

A technique involving a series of DC electrical pulses with different polarities and magnitudes is applied to the analyte sensor, allowing for compensation of reaction time variability and blank current sources without explicit calculation, using enzymes like glucose oxidase to improve accuracy and insensitivity to maltose and oxygen levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional electrochemical methods are used to measure analyte concentration, then the measurement process is simple and fast, but the accuracy is reduced due to variability in reaction rates and interference from substances like maltose and oxygen

Engineering Contradiction:
Improveaccuracy of analyte concentration measurementVSAvoidcomplexity of measurement process
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The measurement process is divided into multiple sequential DC electrical pulses with different polarities and magnitudes. Each pulse serves a specific function: the first pulse (positive polarity) oxidizes interfering substances and generates analyte signal, the second pulse (negative polarity) reduces oxygen and other interferents, and subsequent pulses complete the compensation cycle. This segmentation allows systematic compensation of interference sources without requiring a single complex measurement step.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs periodic application of DC electrical pulses with alternating polarities to the electrochemical sensor. This periodic action enables cyclic compensation of interference sources - oxidizing interferents during positive pulses and reducing them during negative pulses - thereby maintaining measurement accuracy over time without requiring continuous complex corrections.

Inventive Principle:
Principle #19Periodic action

2Reliability

If multiple DC electrical pulses with different polarities and magnitudes are applied to compensate for interference, then the accuracy and reliability of analyte measurement is improved, but the complexity of the measurement process increases

Engineering Contradiction:
Improvereliability of measurement under varying conditionsVSAvoidcomplexity of electrical pulse sequence
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent systematically varies multiple parameters of the applied electrical pulses including polarity (positive/negative), magnitude (different voltage levels), and timing (sequential application). These parameter changes enable selective oxidation and reduction of different interfering substances while maintaining analyte signal integrity. The controlled variation of electrical parameters provides reliable compensation across diverse sample conditions without requiring physical modification of the sensor system.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If enzymes like glucose oxidase are used to improve insensitivity to maltose and oxygen, then the specificity and accuracy are enhanced, but the reaction time variability and susceptibility to other interfering substances remain

Engineering Contradiction:
Improvespecificity to glucose analyteVSAvoidreaction time variability and interference from other substances
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent converts harmful interfering substances into beneficial compensation signals. By applying electrical pulses that oxidize interferents during the first pulse and reduce them during subsequent pulses, the system transforms the presence of interfering substances into measurable compensation signals. This allows the interference to be quantified and subtracted from the total signal, thereby improving accuracy rather than merely tolerating the interference.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The measurement system incorporates feedback through sequential electrical pulses where the response to each pulse informs subsequent measurements. The current generated during oxidation of interferents and analyte in the first pulse provides feedback that is used to compensate for interference in the analyte signal. This feedback mechanism continuously adjusts for varying interference levels, reaction rate variations, and changing sample conditions, maintaining measurement precision throughout the test sequence.

Inventive Principle:
Principle #23Feedback

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 enables accurate measurement of analyte concentrations by compensating for reaction time and blank current variations, providing improved accuracy and reliability across different oxygenation levels and maltose concentrations, even in the presence of interfering substances.

Implementation Method 1

the enzyme glucose oxidase which converts the glucose in a blood sample to gluconolactone. This reaction liberates electrons that react with a mediator

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

The meter applies a voltage between two electrodes, which causes the reduced mediator formed during a reaction incubation period to be reconverted to an oxidized mediator. This generates a small current that is read by the meter

Methodology Applied
Scientific EffectElectrochemical reaction: Redox Reactions

Implementation Method 3

A technique involving a series of DC electrical pulses with different polarities and magnitudes is applied to the analyte sensor, allowing for compensation of reaction time variability and blank current sources

Methodology Applied
Scientific EffectElectrochemical sensing: Conduction (electrical)

Data Source

PatentEP3901624B1Methods to compensate for sources of error during electrochemical testing
Publication Date: 2024.01.31 ROCHE DIABETES CARE GMBH
  • EP3901624B1 patent drawingFigure 1
  • EP3901624B1 patent drawingFigure 2
  • EP3901624B1 patent drawingFigure 3

AI summary

A technique for determining analyte concentration includes applying a first electrical potential excitation pulse to a body fluid sample in an analyte sensor, and a first current response of the body fluid sample to the first pulse is measured. A second excitation pulse is applied to the body fluid sample in the analyte sensor, and a second current response of the body fluid sample to the second pulse is measured. An analyte level in the body fluid sample is determined by compensating for sources of error based on the first current response to the first pulse.