Helminth Assay Carrier Segmentation for Diagnostic Specificity

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Solution Overview

Problem

Current assays for detecting Echinococcus infections, particularly those distinguishing between Echinococcus multilocularis and Echinococcus granulosus, face limitations in diagnostic reliability, sensitivity, and specificity due to batch-to-batch variations, cross-reactivity, and the difficulty in distinguishing between antibodies to specific polypeptides.

Innovation Solution

A diagnostically useful carrier is developed to specifically capture antibodies to p21 and other polypeptides from Echinococcus multilocularis, using a kit that includes means for detecting these antibodies, enhancing the sensitivity and reliability of the assay by separating polypeptides according to molecular weight and using recombinant and purified proteins to distinguish between antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional immunoassays based on native antigens are used, then the assay can detect Echinococcus infections, but the diagnostic reliability and sensitivity are limited due to batch-to-batch variation and cross-reactivity

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidsensitivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent segments the complex native antigen into individual purified polypeptides (p7, p16/18, p21, p25/26) with distinct molecular weights. This segmentation allows each polypeptide to be separately detected and analyzed, eliminating the batch-to-batch variation inherent in whole-antigen preparations while enabling more precise diagnostic measurements through standardized molecular weight-based identification.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent extracts specific polypeptides of interest (p7, p16/18, p21, p25/26) from the complex native antigen through purification processes. By taking out these specific components, the assay eliminates cross-reactivity from other antigen components while maintaining detection capability for Echinococcus infections, thereby improving both reliability and sensitivity.

Inventive Principle:
Principle #2Taking out (Extraction)

2Ease of manufacture

If native antigens from whole worms are used, then the assay can be performed with commercially available reagents, but cross-reactivity occurs between different helminth species reducing specificity

Engineering Contradiction:
Improvecommercial availabilityVSAvoidspecificity
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent extracts and purifies specific polypeptides (p7, p16/18, p21, p25/26) from native antigens to create highly specific diagnostic reagents. This extraction eliminates cross-reactive components present in whole-worm antigens while maintaining the ability to detect Echinococcus-specific antibodies, thereby improving specificity without sacrificing manufacturability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality by selecting polypeptides with specific molecular weights (7 kDa, 16/18 kDa, 21 kDa, 25/26 kDa) that exhibit Echinococcus-specific immunogenicity. Each purified polypeptide possesses localized diagnostic quality tailored to detect specific antibody responses, enhancing specificity while allowing for standardized production protocols.

Inventive Principle:
Principle #3Local quality

3Loss of information

If antibodies to multiple polypeptides are detected simultaneously, then the diagnostic information is comprehensive, but it becomes difficult to distinguish between antibodies to specific polypeptides

Engineering Contradiction:
Improvecomprehensive diagnostic informationVSAvoidpolypeptide-specific antibody distinction
Core Design Contradiction:
Loss of informationVSDifficulty of detecting and measuring

Solution Approach 1:

The patent segments the detection process by assigning each purified polypeptide (p7, p16/18, p21, p25/26) a distinct molecular weight marker. This segmentation allows simultaneous detection of multiple antibodies while maintaining clear distinction between them through gel electrophoresis separation and specific molecular weight identification of each band.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs visualization techniques where different polypeptide bands are distinguished by their positions and characteristics on the gel matrix. The distinct molecular weights create separable bands that can be individually identified and analyzed, allowing comprehensive diagnostic information to be obtained while maintaining clear polypeptide-specific distinction.

Inventive Principle:
Principle #32Color 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 solution significantly improves the sensitivity and specificity of Echinococcus infection detection, allowing for effective differentiation between Echinococcus multilocularis and Echinococcus granulosus infections, with a sensitivity of 93% and specificity of 100% as demonstrated in the study.

Implementation Method 1

a means for specifically capturing an antibody to p21 from Echinococcus multilocularis in a sample from a subject

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

a means for detecting any captured antibody

Methodology Applied
Scientific EffectImmunoassay detection:

Data Source

PatentEP3156798B1A novel assay for the diagnosis of helminth infections
Publication Date: 2018.12.12 EUROIMMUN MEDIZINISCHE LABORDIAGNOSTIKA
  • EP3156798B1 patent drawingFigure 1
  • EP3156798B1 patent drawingFigure 2
  • EP3156798B1 patent drawingFigure 3

AI summary

The present invention relates to a diagnostically useful carrier comprising a means for specifically capturing an antibody to p21 from Echinococcus multilocularis in a sample from a subject; a kit comprising the diagnostically useful carrier, preferably further comprising a means for detecting any captured antibody; a method comprising the step detecting the presence or absence of an antibody to p21 from Echinococcus multilocularis in a sample from a subject; a use of p21 from Echinococcus multilocularis or a variant thereof for increasing the diagnostic reliability, preferably the sensitivity of an assay for the detection of an Echinococcus infection, preferably for distinguishing an Echinococcus multilocularis infection from an Echinococcus granulosus infection; a polypeptide running at a molecular weight of 21 kDa from Echinococcus multilocularis, obtainable by separating according to molecular weight an extract from Echinococcus multilocularis using gel electrophoresis, or a variant thereof, or an antibody to said polypeptide.