Alpha-Keto Acid Peroxide Suppression in Clinical Diagnostics

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Solution Overview

Problem

The hydrogen peroxide quantification system in clinical diagnostics is susceptible to interference from peroxides, leading to inaccurate measurements due to their positive influence on the system, particularly in the presence of surfactants like polyoxyalkylene surfactants which form peroxides during storage or in biological samples.

Innovation Solution

Incorporating an α-keto acid, such as pyruvic acid, in the measurement method to convert components into hydrogen peroxide, which suppresses the influence of peroxides without affecting the hydrogen peroxide quantification system, allowing for accurate measurement of components in biological samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polyoxyalkylene surfactants are used in the hydrogen peroxide quantification system, then enzyme specificity and reactivity are controlled, but peroxides are formed that give measurement values higher than theoretical values

Engineering Contradiction:
Improveenzyme specificity and reactivity controlVSAvoidmeasurement value accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent introduces an iron-cyano compound as an intermediary substance that specifically reacts with peroxides to form a colored complex. This mediator allows the detection and quantification of peroxide interference, enabling correction of measurement values to achieve accurate results while maintaining the beneficial effects of surfactants in the enzymatic reaction system.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If peroxides are present in biological samples or reagents, then they provide positive influence on the hydrogen peroxide quantification system, but they cause deterioration in reagent performance and give measurement values higher than theoretical values

Engineering Contradiction:
Improvehydrogen peroxide signal enhancementVSAvoidmeasurement value accuracy
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent converts the harmful effect of peroxide contamination into a beneficial analytical signal. By utilizing the fact that peroxides produce a positive influence on the hydrogen peroxide quantification system, the invention measures peroxide levels through the same detection mechanism, then applies correction factors to obtain accurate measurements of the target analyte.

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

3Ease of operation

If bilirubin or hemoglobin is present in the biological sample, then the measurement system receives negative influence, but the hydrogen peroxide quantification system remains the preferred method due to mild reaction conditions

Engineering Contradiction:
Improvemild reaction conditions and convenient operationVSAvoidmeasurement value accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent implements a feedback mechanism where peroxide levels are measured using the hydrogen peroxide quantification system itself, and this information is used to correct subsequent measurements. The system continuously monitors peroxide interference and adjusts measurement values accordingly, maintaining both the ease of operation and improved measurement precision.

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

The use of α-keto acids effectively suppresses the impact of peroxides, providing more accurate measurements by maintaining the integrity of the hydrogen peroxide quantification system, as demonstrated in various examples with different kits and chromogens.

Implementation Method 1

The component to be measured in the biological sample is measured by, for example, an enzymatic method... converting the component to be measured into hydrogen peroxide by the action of oxidase

Methodology Applied
Scientific EffectEnzymatic oxidation: Enzyme

Implementation Method 2

reacting the formed hydrogen peroxide, in the presence of a peroxidase, with an oxidative-coloring chromogen, and measuring the absorbance of the resulting dye

Methodology Applied
Scientific EffectPeroxidase-catalyzed oxidation: Enzyme

Implementation Method 3

measuring the absorbance of the resulting dye

Methodology Applied
Scientific EffectAbsorbance measurement: Absorption Spectroscopy

Implementation Method 4

Pyruvic acid, one of α-keto acids, is formed as an intermediate product in the in vivo glycolytic system. The pyruvic acid is known to have relatively strong antioxidative activity

Methodology Applied
Scientific EffectAntioxidative activity: Oxidation

Data Source

PatentEP2653551B1Method for measuring component to be measured
Publication Date: 2018.02.07 KYOWA MEDEX CO LTD
  • EP2653551B1 patent drawingFigure 1
  • EP2653551B1 patent drawingFigure 2
  • EP2653551B1 patent drawingFigure 3

AI summary

The present invention provides a method for measuring a component to be measured in a sample, comprising converting the component to be measured in the sample into hydrogen peroxide and measuring the formed hydrogen peroxide in the presence of an α-keto acid using an oxidative-coloring chromogen. The present invention also provides a method for suppressing the influence of a peroxide on a method of converting a component to be measured in a sample into hydrogen peroxide and measuring the formed hydrogen peroxide using an oxidative-coloring chromogen, the suppression method comprising using an α-keto acid. The measuring method and the suppression method of the present invention using an α-keto acid suppress the influence of a peroxide to give an accurate measurement of the component to be measured in the sample.