Competitive Lateral Flow Assay for Neutralizing Antibody Detection
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Solution Overview
Problem
Current point-of-care assays, such as lateral flow immunoassays, face challenges with sensitivity and specificity in detecting neutralizing antibodies, particularly for viruses like SARS-CoV-2, due to structure-based recognition methods, which are not effective for rapid and large-scale epidemic surveillance.
Innovation Solution
Development of a competitive lateral flow assay that detects neutralizing antibodies based on their functional attribute of blocking molecular interactions, using non-antibody molecules with high binding affinity, allowing for rapid detection of virus-neutralizing antibodies by interrogating samples for interaction-blocking characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If structure-based recognition methods (immobilized antibodies recognizing unique structures/epitopes) are used in lateral flow assays, then the assay can detect target molecules, but the sensitivity and specificity are unsatisfactory
Solution Approach 1:
The patent changes the detection parameter from structure-based recognition to function-based recognition. Instead of detecting unique structural epitopes on antibodies, the assay detects the functional ability of neutralizing antibodies to block the interaction between viral surface polypeptides and cell-surface polypeptides. This parameter change enables more sensitive and specific detection of neutralizing antibodies.
Solution Approach 2:
The patent introduces molecular binding pairs (viral surface polypeptide and cell-surface polypeptide) as intermediaries to detect neutralizing antibodies. Rather than directly detecting antibody structure, the assay uses these molecular intermediaries that naturally interact with the target antibody, allowing the antibody's neutralizing function to be detected through its effect on the intermediary binding interaction.
2Ease of operation
If traditional lateral flow immunoassays are used for point-of-care testing, then the assay is simple and rapid, but the sensitivity and specificity are insufficient for clinical applications
Solution Approach 1:
The patent maintains the simplicity of lateral flow assay operation while changing the detection parameter from structural to functional recognition. The functional assay detects whether antibodies can block viral-cell interactions, providing clinically relevant sensitivity and specificity without compromising the ease of operation.
Solution Approach 2:
The patent substitutes the mechanical/chemical recognition mechanism (antibody-epitope binding) with a biological functional mechanism (viral-cell interaction blocking). This substitution replaces the traditional immunoassay recognition system with a more physiologically relevant system that maintains operational simplicity while improving measurement precision.
3Ease of manufacture
If structure-based detection methods are used, then the assay design is straightforward, but the assay cannot effectively detect neutralizing antibodies for epidemic surveillance
Solution Approach 1:
The patent changes the detection parameter to functional neutralization capability, which is directly relevant to epidemic surveillance needs. This parameter change makes the assay adaptable for detecting protective immunity and monitoring population immunity levels, while the functional assay format remains relatively simple to manufacture.
Solution Approach 2:
The patent creates a universal functional assay platform that can detect neutralizing antibodies against different viruses by simply changing the molecular binding pair (viral surface polypeptide and cell-surface polypeptide). This multi-functional design enables the same assay format to be applied to various viral pathogens for epidemic surveillance.
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, convenient, and point-of-care testing for neutralizing antibodies, overcoming the limitations of traditional assays by providing sensitive and specific results within 15 minutes, suitable for large-scale population surveys during outbreaks like the COVID-19 pandemic.
Implementation Method 1
wherein the first end region of the chromatographic strip is in direct fluid flow communication with the second end region of the binding pad
Implementation Method 2
a first test zone, wherein the first molecular component is immobilized within the first test zone; and a sample binding zone comprising a binding pad... wherein the binding pad comprises the second molecular component labeled with a detection agent
Data Source
AI summary
The present disclosure provides assays, such as lateral flow assays, and components thereof for detection of an analyte, e.g., a neutralizing antibody, that blocks binding of a first molecular component and a second molecular component of a molecular binding pair. In some embodiments, the disclosed assays and components thereof enable the rapid detection of a SARS-CoV-2 neutralizing antibody in a sample from an individual. Also provided in other aspects of the disclosure are devices, methods of making and using, and kits of the assays described herein.