Small Molecule Fluorophore-Labelled Antigens for Autoantibody Detection

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Solution Overview

Problem

Current methods for detecting autoantibodies in autoimmune disorders, such as ELISA and Ouchterlony double immunodiffusion assays, face challenges with sensitivity and specificity, leading to false negatives and false positives, which can delay diagnosis and treatment.

Innovation Solution

The use of small molecule fluorophore-labelled target antigens (SMFLTAs) derived from nuclear autoantigens like Jo-1, Ro60, SSA, SSB, Sm, Sm/RNP, and Scl-70, which are specifically associated with autoimmune diseases, for fluorescence detection in immunoprecipitation assays like double immunodiffusion and counter-immunoelectrophoresis, enhancing sensitivity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ELISA or Ouchterlony double immunodiffusion assays are used to detect autoantibodies, then the diagnostic process can be performed with conventional methods, but the sensitivity and specificity are insufficient leading to false negatives and false positives

Engineering Contradiction:
Improvedetection sensitivity and specificityVSAvoiddiagnostic accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the detection method from conventional ELISA or Ouchterlony assays to immunoprecipitation assays using small molecule fluorophore-labelled antigens. This changes the detection parameters (fluorescence detection vs. conventional readout) to achieve higher sensitivity and specificity, directly resolving the contradiction between measurement precision and diagnostic reliability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical/conventional detection systems (ELISA plate reading, visual inspection of precipitin lines) with fluorescence detection systems. This substitution enables more precise measurement of autoantibody-antigen interactions, eliminating the false positives and negatives inherent in conventional methods

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Loss of time

If conventional detection methods are used, then the diagnostic process is simpler, but false positives and false negatives delay diagnosis and treatment

Engineering Contradiction:
Improvediagnosis timeVSAvoiddetection accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent employs preliminary action by using small molecule fluorophore-labelled antigens that are pre-prepared and designed for high-specificity binding. This preliminary preparation ensures that when the assay is performed, the detection is immediately accurate and sensitive, eliminating the need for repeated testing and reducing overall diagnosis time while maintaining high precision

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If small molecule fluorophore-labelled target antigens are used in immunoprecipitation assays, then sensitivity and specificity are enhanced, but the method complexity increases

Engineering Contradiction:
Improveautoantibody detection sensitivityVSAvoidassay method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses small molecule fluorophore-labelled antigens as intermediaries between the autoantibodies in patient samples and the fluorescence detection system. These labelled antigens mediate the specific binding interactions while enabling sensitive detection, effectively bridging the gap between simple sample input and precise measurement output without requiring complex equipment

Inventive Principle:
Principle #24Intermediary (Mediator)

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 provides a more robust diagnostic tool with increased sensitivity and reduced false positives, allowing for earlier and more accurate detection of autoantibodies, potentially reducing the need for additional testing and expediting treatment.

Implementation Method 1

contacting the sample with a small molecule fluorophore-labelled target antigen or a functional fragment, functional variant or functional derivative of an small molecule fluorophore-labelled target antigen that specifically binds to a target antibody

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

detecting the presence of the target antibody bound to the small molecule fluorophore-labelled target antigen by fluorescence detection

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS8883517B2Detection of antibodies
Publication Date: 2014.11.11 GEMINI RES
  • US8883517B2 patent drawing
  • US8883517B2 patent drawing
  • US8883517B2 patent drawing

AI summary

The present invention relates to a method of detecting a target antibody, particularly a target autoantibody, in a sample, using a small molecule fluorophore-labelled target antigen, or a functional fragment, functional variant or functional derivative thereof that specifically binds to the target antibody. Detection is typically carried out using immunodiffusion or immunoelectrophoresis. The invention also relates to methods of diagnosing disease, particularly autoimmune disease, using small molecule fluorophore labelled target antigens and autoantigens. Small molecule fluorophore labelled target antigens, including autoantigens, are also disclosed, as are uses such.