HCV Core Antigen Detection Using Alkaline Detergent Pretreatment

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Solution Overview

Problem

Existing methods for detecting hepatitis C virus (HCV) core polypeptides are prone to false results and interference, leading to unclear or false positives, and do not effectively remove confounding immunoglobulins, which necessitates further costly and time-consuming investigations.

Innovation Solution

A method involving contacting a sample with a base and a cationic detergent, followed by a sandwich immunoassay using capture and detector compounds to detect the HCV core polypeptide, which includes a cationic detergent and optionally a non-ionic detergent, to enhance specificity and reduce interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If acid treatment is used to disassemble viral particles, then sensitivity of the assay is improved, but false positives increase and immunoglobulins are not effectively removed

Engineering Contradiction:
Improvesensitivity of the assayVSAvoidfalse positives
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention changes the chemical parameter from acid treatment to alkaline treatment (pH 11.5-14.0), which fundamentally alters the denaturation mechanism. Alkaline pH causes irreversible denaturation of immunoglobulins while effectively disassembling HCV particles, resolving the contradiction between sensitivity improvement and false positive reduction

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention converts the potentially harmful effect of strong alkaline conditions into a beneficial selective denaturation process. The harsh alkaline environment that could damage proteins is instead used to selectively denature immunoglobulins (reducing false positives) while the cationic detergent protects and solubilizes the viral core polypeptide for detection

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

2Measurement precision

If chaotropic agents are used to disassemble viral particles, then sensitivity is improved, but susceptibility to interference increases

Engineering Contradiction:
ImprovesensitivityVSAvoidsusceptibility to interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention replaces chaotropic agents with a combination of alkaline pH and cationic detergent. This parameter change achieves viral particle disassembly through a different mechanism (alkaline denaturation and detergent solubilization) that is less prone to interference from sample matrix components while maintaining high sensitivity

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If high salt concentrations are used to disassemble viral particles, then sensitivity is improved, but device complexity and cost increase

Engineering Contradiction:
ImprovesensitivityVSAvoidcomplexity of pre-processing
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention changes from high salt concentration treatment to alkaline pH treatment combined with cationic detergent. This simplifies the pre-processing protocol by using a more effective mechanism that requires fewer additional steps and equipment, reducing both device complexity and operational cost while maintaining sensitivity

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 provides a highly sensitive and specific detection of HCV core polypeptides, reducing false positives and interference, thereby improving diagnostic accuracy and efficiency.

Implementation Method 1

contacting said sample with a base and with a surfactant comprising a cationic detergent... contacting said sample with a base thereby creating a reaction mixture... incubating said sample at a pH of at least 11.75... alkaline treatment... causing irreversible denaturation of potentially confounding immunoglobulins

Methodology Applied
Scientific EffectAlkaline denaturation:

Implementation Method 2

contacting said sample with a base and with a surfactant comprising a cationic detergent... aimed at disassembling viral particles in order to increase sensitivity of the assay

Methodology Applied
Scientific EffectDetergent disassembly: Surfactant

Data Source

PatentEP3465217B1Method for serological detection of viral antigens
Publication Date: 2025.09.03 ROCHE DIAGNOSTICS GMBH

AI summary

The present invention relates to a method for detecting a corepolypeptide of a hepatitis C virus (HCV) in a sample from a subject comprising (a) contacting said sample with a base and with a surfactant comprising a cationic detergent, and (b) detecting a corepolypeptide of said HCV in said sample. The present invention further relates to a method for pre-processing a sample from a subject for detection of HCV, comprising contacting said sample with a baseand with a surfactant comprising a cationic detergent; and to a pre-processing reagent for detecting HCV in a sample, comprising a base and a surfactant comprising a cationic detergent, wherein said surfactant further comprises a non-ionic detergent. Moreover, the present invention further relates to kits, uses, and devices related to the methods of the present invention.