Immunochromatography Buffer pH Control for fFN Detection

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Solution Overview

Problem

Immunochromatography methods struggle with cross-reactions and false positive results when detecting analytes contaminated with similar antigens, particularly in the case of oncofetal fibronectin (fFN) due to the similarity with plasma-derived fibronectin, leading to measurement errors and inaccurate determinations.

Innovation Solution

A detection method using immunochromatography that involves a buffer solution with a pH range of 5.0 to 6.7, specifically using a conjugate test strip with a first antibody labeled with a labeling substance and a second antibody immobilized on a membrane, where one antibody is specific to fFN and the other binds to both fFN and plasma fibronectin, reducing cross-reactivity and maintaining detection sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If immunochromatography is used to detect oncofetal fibronectin (fFN), then detection speed and simplicity are improved, but cross-reaction with plasma fibronectin causes measurement errors and false positives

Engineering Contradiction:
Improvedetection speedVSAvoidmeasurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent changes the pH parameter of the buffer solution to a specific range (5.0-6.7, preferably 5.3-6.0) to suppress cross-reaction between antibodies and plasma fibronectin while maintaining detection sensitivity for fFN. This parameter modification resolves the contradiction by allowing rapid immunochromatographic detection without false positives from cross-reactivity with similar antigens.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If a washing step is added to eliminate similar antigens, then measurement accuracy is improved, but the homogeneous method's simplicity and speed are lost

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidmethod complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Instead of adding a washing step that would increase complexity, the patent modifies the pH parameter of the buffer solution used in the existing homogeneous immunochromatography method. This allows the method to remain simple and rapid while achieving accurate results by suppressing cross-reaction through pH control, thus resolving the contradiction without increasing device or procedural complexity.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If antibodies with high specificity to fFN are used, then measurement precision is improved, but cross-reactivity with plasma fibronectin increases due to antigen similarity

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcross-reaction
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the pH parameter of the buffer solution to a specific range (5.0-6.7) that differentiates the binding affinity between fFN-specific antibodies and their targets. At this optimized pH, the antibodies maintain high specificity to fFN while cross-reaction with plasma fibronectin is suppressed, thus resolving the contradiction between detection sensitivity and cross-reactivity.

Inventive Principle:
Principle #35Parameter changes

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 suppresses cross-reactions between antibodies and similar antigens, preventing measurement errors and false positives while maintaining or improving detection sensitivity for fFN, even in specimens contaminated with blood.

Implementation Method 1

bringing the analyte in the sample into contact with the conjugate in the presence of a buffer solution of pH 5.0 to pH 6.7

Methodology Applied
Scientific EffectpH control:

Implementation Method 2

the buffer solution suppresses cross-reactions between an antibody against the analyte and similar antigens

Methodology Applied
Scientific EffectElectrostatic interactions:

Implementation Method 3

a conjugate containing a first antibody labeled with a labeling substance is retained in a part of the spreading portion... detecting a complex of the analyte in the sample and the conjugate in the detecting portion

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 4

a conjugate containing a first antibody labeled with a labeling substance

Methodology Applied
Scientific EffectLabeling:

Data Source

PatentEP3422004B1Method for detecting carcinoembryonic fibronectin using immunochromatography
Publication Date: 2020.09.09 SEKISUI MEDICAL CO LTD
  • EP3422004B1 patent drawingFigure 1~2
  • EP3422004B1 patent drawingFigure 3~4
  • EP3422004B1 patent drawingFigure 5~6

AI summary

The present invention addresses the problem of suppressing cross-reaction with antigenic components similar to an analyte, in immunochromatography, so as to reduce detection of similar antigens, and prevent measurement value errors and false positive reactions, while maintaining or improving the detection sensitivity for the analyte, and thereby allowing accurate determinations. In the present invention, when an antibody that specifically binds to the analyte and the analyte are reacted under conditions in which a buffer solution is used in a specific pH range, even if similar antigens are also present, cross-reactivity between the antibody and similar antigens is suppressed, and the analyte can be accurately detected.