Azide Reagent Suppresses Hemoglobin Interference in Glucose Electrode

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Solution Overview

Problem

The existing enzyme-electrode method for measuring glucose concentration in blood specimens is hindered by hemoglobin, which reacts with hydrogen peroxide, leading to inaccurate results due to the inhibitor's interference, and preventing hemolytic activity is impractical and burdensome.

Innovation Solution

A method involving a reagent with an azide compound as a suppressing agent to transform hemoglobin into methemoglobin, combined with a supporting electrolyte like sodium chloride, is used to suppress the reaction between hydrogen peroxide and hemoglobin, allowing for accurate glucose concentration measurement using an enzyme electrode system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If the enzyme-electrode method is used to measure glucose concentration, then the measurement can be performed automatically, but hemoglobin in the specimen reacts with hydrogen peroxide and inhibits the electrode reaction, reducing measurement accuracy

Engineering Contradiction:
Improveautomatic measurementVSAvoidmeasurement accuracy
Core Design Contradiction:
Extent of automationVSMeasurement precision

Solution Approach 1:

The patent introduces an azide compound as an intermediary substance that selectively reacts with hemoglobin to form methemoglobin, which does not react with hydrogen peroxide. This intermediary action blocks the harmful interaction between hemoglobin and hydrogen peroxide, allowing the glucose measurement to proceed accurately without manual intervention to prevent hemolysis.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the harmful reaction between hemoglobin and hydrogen peroxide into a beneficial process by using the azide compound to transform hemoglobin into methemoglobin. This transformation eliminates the interference while maintaining the automated measurement process, turning the presence of hemoglobin from a problem into a manageable condition.

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

2Measurement precision

If precautions are taken to prevent hemolytic activity during transportation and preservation, then hemoglobin interference can be reduced, but the handling steps become complicated and time-consuming

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidhandling steps
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent enables the measurement system to automatically handle the hemoglobin interference issue through the azide compound, which self-reacts with hemoglobin in the specimen. This eliminates the need for manual precautions during transportation and preservation, as the chemical intervention occurs automatically during the measurement process itself.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The azide compound is pre-added to the reagent, so that when the reagent contacts the blood specimen, the hemoglobin is immediately transformed into methemoglobin before it can interfere with the hydrogen peroxide reaction. This preliminary chemical action prevents the harmful interaction without requiring prior manual intervention.

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If the reaction between hemoglobin and hydrogen peroxide is allowed to proceed, then the electrode output shows lower values, but preventing this reaction requires additional suppressing agents and reagent components

Engineering Contradiction:
Improveoperational simplicityVSAvoidelectrode output accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent combines multiple functions into a single reagent formulation: the azide compound serves both as a hemoglobin suppression agent and as part of the measurement chemistry, while sodium chloride provides both ionic strength adjustment and supports the electrode reaction. This merging of functions maintains operational simplicity while ensuring accurate measurements.

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

This approach improves measurement accuracy and reproducibility by stabilizing the oxidation current and reducing the variability caused by hemoglobin interference, enhancing the reliability of glucose concentration measurements.

Implementation Method 1

an azide compound as a suppressing agent for suppressing the reaction between hydrogen peroxide and hemoglobin by transforming hemoglobin into methemoglobin

Methodology Applied
Scientific EffectChemical reaction (azide-hemoglobin transformation): Chemical Bonding

Implementation Method 2

an enzyme immobilized film 34, a hydrogen peroxide selective transmission film 35, and a hydrogen peroxide electrode 36

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 3

electrons are removed at an electrode from hydrogen peroxide generated by oxidizing glucose with an enzyme

Methodology Applied
Scientific EffectOxidation reaction: Oxidation

Implementation Method 4

a glucose concentration is calculated based on a current value measured at the time in the electrode

Methodology Applied
Scientific EffectElectrochemical measurement: Electrochemiluminescence

Implementation Method 5

sodium chloride or potassium chloride as a supporting electrolyte

Methodology Applied
Scientific EffectElectrolyte conduction: Electrolyte

Data Source

PatentEP2136206B1Method for determining glucose concentration
Publication Date: 2012.04.11 ARKRAY INC
  • EP2136206B1 patent drawingFigure 1~2
  • EP2136206B1 patent drawingFigure 3
  • EP2136206B1 patent drawingFigure 4~5

AI summary

The present invention relates to a method, a reagent and a device for measuring a substrate concentration based on an amount of hydrogen peroxide generated from a substrate. In the present invention, a suppressing agent for suppressing a reaction between the hydrogen peroxide and an inhibitor is added. As the suppressing agent, an azide compound such as sodium azide or a nitrite compound such as sodium nitrite is used. In the invention, a supporting electrolyte, such as sodium chloride or potassium chloride may be further added.