Kidney-Specific Clusterin Detection via Lectin-Antibody Composite Assay

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Solution Overview

Problem

Current methods for detecting kidney-specific clusterin in urine samples are hindered by contamination from serum clusterin, leading to false positive results due to the high concentration of clusterin in serum, which is particularly challenging in veterinary medicine where contamination is more pronounced.

Innovation Solution

The use of specific antibodies and lectins that bind to carbohydrate moieties of kidney-specific clusterin, while avoiding binding to other clusterin isoforms, allows for the detection of kidney-specific clusterin in urine samples, utilizing techniques such as lateral flow assays or ELISA to isolate and quantify the kidney-specific isoform.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If general clusterin detection methods are used, then clusterin can be detected in urine samples, but false positive results occur due to serum contamination

Engineering Contradiction:
Improvedetection accuracyVSAvoiddiagnostic reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention segments clusterin detection into two distinct targets: total clusterin and kidney-specific clusterin. By using sequential detection methods where kidney-specific clusterin is measured after total clusterin, the assay can distinguish between serum contamination (high total, low kidney-specific) and actual kidney damage (high total, high kidney-specific), thereby resolving the false positive problem

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces a differential detection system that acts as an intermediary between general clusterin detection and specific kidney damage diagnosis. By measuring both total clusterin and kidney-specific clusterin levels and comparing them, the system mediates the interpretation of results to eliminate false positives from serum contamination

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If serum clusterin is detected in urine samples, then clusterin concentration can be measured, but diagnostic specificity for kidney damage is reduced

Engineering Contradiction:
Improveclusterin concentrationVSAvoiddiagnostic specificity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The invention applies local quality by developing specific reagents (antibodies or lectins) that recognize only the carbohydrate moieties present on kidney-specific clusterin isoforms. This localized molecular recognition ensures that only the relevant clusterin form is detected, eliminating cross-reactivity with serum clusterin and improving diagnostic specificity

Inventive Principle:
Principle #3Local quality

3Ease of operation

If conventional immunoassays are used for clusterin detection, then detection can be performed, but specificity for kidney-specific isoforms is insufficient

Engineering Contradiction:
Improveassay simplicityVSAvoidisoform specificity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention uses composite detection reagents that combine antibodies (for clusterin backbone recognition) with lectins (for carbohydrate moiety recognition). This composite approach allows conventional immunoassay formats to be used while achieving high isoform specificity through the dual-recognition mechanism

Inventive Principle:
Principle #40Composite materials

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 enables accurate detection and quantification of kidney-specific clusterin, reducing false positives and improving diagnostic specificity for kidney damage or disease, even in the presence of serum contamination.

Implementation Method 1

contacting a sample with one or more antibodies or antigen binding fragments thereof that specifically bind clusterin

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

one or more molecules that specifically bind to carbohydrate moieties of the first clusterin isoform

Methodology Applied
Scientific EffectLectin-carbohydrate binding:

Data Source

PatentEP4019976A1Specific detection of clusterin isoforms
Publication Date: 2022.06.29 IDEXX LABORATORIES INC
  • EP4019976A1 patent drawingFigure 1A~1B
  • EP4019976A1 patent drawingFigure 2
  • EP4019976A1 patent drawingFigure 3

AI summary

The present invention relates to methods and compositions for the detection of specific isoforms of clusterin.