Lateral Flow Test for Neutralizing Antibody Detection
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Solution Overview
Problem
Conventional lateral flow tests are limited in detecting neutralizing antibodies and cannot differentiate between neutralizing and non-neutralizing antibodies, and they are not suitable for non-human samples or for detecting IgA and IgM antibodies, requiring multiple antibodies and laborious, expensive conventional tests for accurate results.
Innovation Solution
A 'double antigen' lateral flow test with the same antigen on both the conjugate pad and test area, and an 'antigen-receptor' test with a receptor molecule, allowing for kinetic analysis of antibody-antigen binding, enabling detection of neutralizing antibodies without species-specific antibodies and distinguishing between neutralizing and non-neutralizing antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional lateral flow tests use anti-human IgG antibodies in the test area, then human IgG antibodies can be detected, but the test cannot detect non-human samples or other antibody isotypes (IgA, IgM)
Solution Approach 1:
The patent employs a species-independent detection approach by using a capture molecule that binds to a constant region common to all antibody isotypes (IgG, IgA, IgM) rather than isotype-specific antibodies. This allows a single test design to detect antibodies from different species and isotypes, achieving universality without requiring multiple different capture antibodies in the test area
Solution Approach 2:
Instead of using anti-antibody molecules (which are species and isotype specific), the patent inverts the approach by using antigen molecules themselves as capture agents. The antigen binds directly to antibodies in the sample, eliminating the need for species-specific anti-Ig antibodies and enabling detection across different species and isotypes with a single test design
2Measurement precision
If whole spike protein is used as antigen, then total antibody titre can be determined, but information on neutralising antibody titre specifically is not provided
Solution Approach 1:
The patent divides the detection into multiple test areas: one test area uses the whole spike protein as antigen to detect total anti-SP antibodies, while another test area uses the receptor binding domain (RBD) as antigen to detect potentially neutralising antibodies. This segmentation allows simultaneous measurement of both total antibody titre and neutralising antibody titre, preserving all relevant information
Solution Approach 2:
The patent adds a functional dimension to the detection by including a receptor test area that measures the ability of antibodies to block the interaction between spike protein and host receptor. This functional assay dimension complements the binding assays, providing both quantitative titre information and qualitative neutralisation capability assessment
3Measurement precision
If conventional neutralisation tests are used as gold standard, then accurate neutralising antibody titre can be measured, but the tests are laborious, expensive, require hazardous reagents, sophisticated equipment, and may take days to obtain results
Solution Approach 1:
The patent replaces the complex mechanical and biological systems of conventional neutralisation tests (live cell cultures, plaque formation, sophisticated equipment) with a simplified lateral flow immunoassay system. The assay uses antigen-antibody binding on a membrane strip with visual or optical detection, eliminating the need for cell cultures, hazardous live viruses, and sophisticated equipment while maintaining measurement accuracy
Solution Approach 2:
The patent changes the detection parameters from measuring plaque formation over days to measuring antigen-antibody complex formation in hours. By using labelled antigens and detectable markers in a lateral flow format, the assay compresses the measurement time from days to hours while maintaining the essential functional assessment of neutralising antibody activity
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
Enables rapid, species-independent detection of neutralizing antibodies, including IgA and IgM, and provides kinetic information on antibody binding, improving accuracy and reducing the need for extensive, costly conventional tests.
Implementation Method 1
a lateral flow device includes a series of regions on a capillary bed which will transport a sample
Implementation Method 2
Antibodies within the sample will bind these labelled antigens
Implementation Method 3
The detectable label ensures that these can then be detected
Data Source
AI summary
A lateral flow test device and method for using same are provided. The device includes epitope test regions having a fragment of an antigenic protein and a full length antigenic protein, and a receptor test region having a receptor for the antigenic protein. Test samples are added to a conjugate pad including free labelled antigenic protein fragments. Neutralising antibodies in the test sample bind to the free labelled antigenic protein, and are detected by the test regions. Binding kinetics and other characteristics of the antibodies can be investigated by monitoring development of label at the test regions, and comparing the same at different test regions. Embodiments describe use for determining antibodies to SARS-COV-2, using RBD fragments, spike proteins, and human ACE2 receptors, at the respective test regions.