Antibody Detection via Aggregating Agent Signal Amplification

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Solution Overview

Problem

Current methods for detecting antibodies, particularly for diseases like COVID-19, are not sufficiently sensitive, fast, or practical for point-of-care and high-throughput screening, requiring improvements in sensitivity and speed for effective diagnosis.

Innovation Solution

A method involving a biological sample contacted with an antibody binding agent containing a detectable label and an aggregating agent, which forms a detectable antibody-antibody binding agent aggregate, allowing for rapid detection of antibodies through imaging techniques like fluorescent microscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional antibody detection methods are used, then detection can be performed, but sensitivity and speed are insufficient for point-of-care applications

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent introduces an aggregating agent as an intermediary component that binds to both the antibody-antigen complex and forms visible aggregates. This mediator amplifies the detection signal by clustering multiple antibody-antigen complexes into visible aggregates, thereby enhancing sensitivity without requiring complex instrumentation or lengthy procedures.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs detectable labels that produce visual color changes or fluorescent signals when bound to antibodies. The aggregating agent concentrates these labeled antibodies into visible aggregates, creating a macroscopic color or fluorescence change that can be detected by the naked eye or simple imaging devices, enabling rapid and sensitive detection without complex equipment.

Inventive Principle:
Principle #32Color changes

2Productivity

If conventional antibody detection methods are used, then detection can be performed, but the methods are not practical for high-throughput screening

Engineering Contradiction:
Improvescreening throughputVSAvoiddetection system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent divides the detection system into separate, modular components: antibody binding agents with detectable labels, aggregating agents, and simple detection reagents. This segmentation allows each component to be independently optimized and combined in high-throughput formats such as microplates or microarrays, enabling parallel processing of multiple samples simultaneously without requiring complex integrated systems.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The aggregating agent serves as a universal intermediary that can be used across different antibody detection applications. This single component amplifies signals from various antibody-antigen interactions, allowing the same simple detection platform to handle diverse samples and targets, thereby increasing throughput without proportionally increasing system complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Speed

If conventional antibody detection methods are used, then detection can be performed, but speed is insufficient for rapid diagnosis

Engineering Contradiction:
Improvedetection speedVSAvoiddetection sensitivity
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The patent performs preliminary binding between the antibody binding agent and target antibody in the sample before adding the aggregating agent. This pre-binding step allows specific antibody-antigen complexes to form first, ensuring specificity, while the subsequent addition of the aggregating agent rapidly amplifies the signal. This two-step approach maintains sensitivity while enabling faster total detection time compared to methods requiring lengthy single-step reactions.

Inventive Principle:
Principle #10Preliminary action

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 method enables rapid and sensitive detection of antibodies, with results achievable within minutes to days, improving diagnostic capabilities for diseases such as COVID-19 and offering potential for point-of-care applications.

Implementation Method 1

contacting a biological sample with an antibody binding agent, wherein the antibody binding agent comprises an antibody binding antigen and a detectable label, wherein the antibody binding agent binds an antibody in the biological sample

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

adding an aggregating agent to the biological sample, wherein the aggregating agent binds to the antibody and forms an antibody-antibody binding agent aggregate

Methodology Applied
Scientific EffectAggregation:

Implementation Method 3

the detectable label comprises a fluorophore. In some embodiments, the fluorophore comprises a green fluorescent protein (GFP)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 4

the detectable label comprises a bioluminescent label. In some embodiments, the bioluminescent label comprises Gaussia luciferase (Gluc)

Methodology Applied
Scientific EffectBioluminescence: Bioluminescence

Data Source

PatentUS20230349904A1Methods for detecting antibodies
Publication Date: 2023.11.02 RGT UNIV OF CALIFORNIA
  • US20230349904A1 patent drawing
  • US20230349904A1 patent drawing
  • US20230349904A1 patent drawing

AI summary

Provided herein are methods of preparing a detectable antibody-antibody binding agent aggregate, the method comprising: (a) contacting a biological sample with an antibody binding agent, wherein the antibody binding agent comprises an antibody binding antigen and a detectable label, wherein the antibody binding agent binds an antibody in the biological sample; (b) adding an aggregating agent to the biological sample, wherein the aggregating agent binds to the antibody and forms an antibody-antibody binding agent aggregate; and (c) detecting a signal from the detectable label of the antibody binding agent associated with the antibody-antibody binding agent aggregate, thereby preparing a detectable antibody-antibody binding agent aggregate.