Urinary Protein Reagent Composition for Hemoglobin Interference Control

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Solution Overview

Problem

Existing methods for quantifying protein in urine using metal-dye complexes face issues with hemolytic hemoglobin interference and reactivity differences between protein species, particularly when sodium dodecyl sulfate (SDS) is used to correct these differences, leading to inaccurate results.

Innovation Solution

A method and reagent that utilize a specific combination of anionic and polyoxyalkylene-type nonionic surfactants with a metal-dye complex to react with protein, reducing hemolytic hemoglobin interference and correcting reactivity differences, using surfactants such as sulfonic acid-type and sulfuric acid ester-type anionic surfactants alongside polyoxyalkylene-type nonionic surfactants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sodium dodecyl sulfate (SDS) is added to correct reactivity difference between albumin and globulin, then reactivity difference is eliminated, but hemolytic hemoglobin interference increases

Engineering Contradiction:

Improvereactivity uniformityVSAvoidhemolytic hemoglobin interference

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a polyoxyalkylene-type nonionic surfactant as an intermediary substance that mediates between the anionic surfactant (SDS) and hemolytic hemoglobin. The nonionic surfactant has affinity for both proteins and hemoglobin, forming mixed micelles that reduce the direct interaction between SDS and hemoglobin, thereby suppressing hemolytic hemoglobin interference while maintaining the reactivity-correcting function of SDS.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite surfactant system combining anionic surfactant (SDS) and polyoxyalkylene-type nonionic surfactant in specific ratios. This composite system leverages the reactivity-correcting capability of SDS while the nonionic component suppresses hemoglobin interference, achieving both objectives simultaneously through synergistic interaction.

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If metal-dye complex is used for protein quantification, then protein measurement is achieved, but hemolytic hemoglobin interference occurs

Engineering Contradiction:

Improveprotein quantification accuracyVSAvoidhemolytic hemoglobin interference

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The polyoxyalkylene-type nonionic surfactant acts as an intermediary that protects the metal-dye complex-protein reaction from interference by hemolytic hemoglobin. The nonionic surfactant binds to hemoglobin and prevents it from interfering with the colorimetric reaction, while allowing the metal-dye complex to react normally with proteins.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of operation

If single-solution reagent is used, then operation simplicity is improved, but reactivity difference between protein species occurs

Engineering Contradiction:

Improveoperation simplicityVSAvoidreactivity uniformity

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent merges multiple functions into a single reagent solution by combining the metal-dye complex, anionic surfactant (SDS), and polyoxyalkylene-type nonionic surfactant in one formulation. This single-solution reagent simultaneously achieves protein quantification, reactivity correction between albumin and globulin, and suppression of hemolytic hemoglobin interference, eliminating the need for separate correction steps.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The single-solution reagent exhibits multi-functionality: it serves as both the coloring reagent for protein detection and the corrective agent for reactivity differences and hemoglobin interference. The carefully balanced composition allows one solution to perform multiple corrective functions that traditionally required separate reagents or pretreatment steps.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 effectively reduces hemolytic hemoglobin interference and corrects reactivity differences between protein species in urine, providing accurate protein quantification using a single-solution reagent suitable for clinical applications.

Implementation Method 1

using a complex in which a metal is coordinated to a dye and an absorption wavelength of which shifts in the presence of the protein

Methodology Applied

Scientific EffectAbsorption wavelength shift: Absorption Spectroscopy

Implementation Method 2

reacting the protein with the complex in presence of at least one anionic surfactant selected from a sulfonic acid-type anionic surfactant and a sulfuric acid ester-type anionic surfactant; and a polyoxyalkylene-type nonionic surfactant

Methodology Applied

Scientific EffectSurfactant action: Surfactant

Data Source

PatentEP4703728A1Method and reagent for quantifying urinary protein

Publication Date: 2026.03.04 NITTO BOSEKI CO LTD

AI summary

The present invention provides a method and a reagent for reducing hemolytic hemoglobin interference while correcting a difference in reactivity between urinary protein types. Provided is a reagent for measuring protein in urine, comprising: a complex in which a metal is coordinated to a dye and the absorption wavelength of which shifts upon protein binding thereto; at least one anionic surfactant selected from a sulfonic acid-type anionic surfactant and a sulfuric acid ester-type anionic surfactant; and a polyoxyalkylene-type nonionic surfactant.