Calixarene Macrocyclic Compound Immunoassay Sensitivity Hemoglobin Interference

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Solution Overview

Problem

Current immunoassay methods face challenges in enhancing measurement sensitivity and avoiding the influence of hemoglobin, which affects the accuracy of assays, particularly in plasma-derived samples, as existing additives either fail to provide stable sensitivity enhancement or decrease measurement precision.

Innovation Solution

The use of a macrocyclic compound, such as calixarene, at a low final concentration of 0.005 to 4 mM in the reaction system enhances measurement sensitivity and prevents hemoglobin interference, allowing for accurate detection of low-concentration target substances without lot-to-lot variation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If polyethylene glycol or dextran is added to enhance measurement sensitivity, then measurement sensitivity is improved, but stable sensitivity-enhancing effect cannot be attained due to molecular weight distribution

Engineering Contradiction:
Improvemeasurement sensitivityVSAvoidstability of sensitivity-enhancing effect
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical parameter from polymers with molecular weight distribution (polyethylene glycol, dextran) to a single compound with defined molecular weight (calixarene). This parameter change eliminates the instability caused by polydisperse molecular weights while maintaining the sensitivity-enhancing effect through the specific cavity structure of calixarene molecules.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If a surfactant is added to avoid hemoglobin influence, then hemoglobin interference is reduced, but measurement sensitivity decreases

Engineering Contradiction:
Improvehemoglobin interferenceVSAvoidmeasurement sensitivity
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent introduces calixarene as an intermediary substance that selectively binds to hemoglobin through its cavity structure, preventing hemoglobin from interfering with the antigen-antibody reaction. This intermediary approach avoids the use of surfactants that would non-specifically reduce measurement sensitivity while still eliminating hemoglobin interference.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If conventional additives are used to improve measurement sensitivity, then sensitivity enhancement is achieved, but lot-to-lot variation occurs reducing assay precision

Engineering Contradiction:
Improvemeasurement sensitivityVSAvoidassay precision across batches
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent changes from using polymeric additives with inherent molecular weight distributions to a single compound (calixarene) with a precise molecular weight of 720. This parameter change eliminates lot-to-lot variation, as each calixarene molecule has identical binding properties, ensuring consistent assay performance across different batches.

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

The method effectively increases measurement sensitivity and prevents hemoglobin interference, enabling accurate assays even in samples with low target substance concentrations, while maintaining stable precision across different batches.

Implementation Method 1

non-specific reaction with various miscellaneous substances contained in a sample other than the target antigen-antibody reaction causes aggregation or absorption

Methodology Applied
Scientific EffectNon-specific reaction prevention:

Implementation Method 2

Particularly when a plasma-derived biological sample containing hemoglobin originating from hematocytes is assayed, hemoglobin may influence obtaining accurate measurements of immunoassay

Methodology Applied
Scientific EffectHemoglobin interference prevention:

Data Source

PatentEP2295969B1Method for enhancing sensitivity or method for avoiding influence of hemoglobin in immunological measurement
Publication Date: 2016.05.18 SEKISUI MEDICAL CO LTD

AI summary

To provide a technique for enhancing measurement sensitivity or a technique for avoiding a hemoglobin influence in an immunoassay method. The invention is directed to a method for enhancing measurement sensitivity or a hemoglobin influence avoiding method in an immunoassay method, characterized in that the method includes assaying target substance contained in a biological sample through antigen-antibody reaction in the presence of a macrocyclic compound.