Lateral Flow Label Complex for High Molecular Weight Detection

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Solution Overview

Problem

Traditional sandwich assays and lateral flow tests face issues such as the 'hook effect' and steric hindrance when detecting high-molecular weight analytes like proteins, leading to false negatives and impaired test functionality.

Innovation Solution

A lateral flow apparatus with a label complex comprising two antibodies, an antibody binding protein, and a detectable component, where one antibody is an antispecies antibody and the other has sensitivity to the control area capture agent, is used to detect high-molecular weight substances, reducing the hook effect and steric hindrance by providing a spacer arm and independent affinity to the label complex.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a traditional sandwich assay format is used to detect analytes, then the assay can detect the presence of analytes using capture agents and labeled receptors, but the hook effect occurs at higher analyte concentrations leading to false negative results

Engineering Contradiction:
Improvedetection accuracyVSAvoidfalse negative rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention introduces an antibody binding protein as an intermediary component in the label complex. This protein binds to both the analyte and the antispecies antibody, creating a mediated detection system. The intermediary structure prevents the direct competition between analyte and labeled receptor that causes the hook effect, allowing accurate detection across a wider concentration range without false negatives

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The label complex is segmented into multiple functional components: an antibody specific to the analyte, an antibody binding protein, and an antispecies antibody. This segmentation allows each component to perform its specific function independently, preventing the overwhelming of capture agents by unlabeled analyte and eliminating the hook effect

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If lateral flow tests are used to detect high molecular weight molecules such as proteins, then the test can identify the presence of these molecules, but steric hindrance impairs the effective functioning of the test

Engineering Contradiction:
Improvedetection capabilityVSAvoidsteric hindrance
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The antibody binding protein serves as a mediator that bridges the analyte and the detection system. This intermediary structure reduces steric hindrance by providing an extended binding interface, allowing the large protein molecules to bind effectively without blocking critical binding sites

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The label complex adds a dimensional aspect to the detection by incorporating multiple binding interfaces in three-dimensional space. The antibody-binding protein-antispecies antibody structure creates additional spatial dimensions for binding, reducing steric interference from large analyte molecules

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 allows for accurate and efficient detection of high-molecular weight substances like allergenic proteins without the drawbacks of traditional methods, providing clear positive or negative results and reducing interference from large molecules.

Implementation Method 1

The antibody binding protein is binding to a receptor for the analyte and to the anti-species antibody

Methodology Applied
Scientific EffectAntibody-antigen binding:

Implementation Method 2

The detectable component is bound to the antibody binding protein

Methodology Applied
Scientific EffectDetectable component signal:

Implementation Method 3

the control area capture agent may be characterized by an affinity to the label complex that is independent of the label complex being bound by the analyte

Methodology Applied
Scientific EffectAffinity binding:

Data Source

PatentEP2715358B1Lateral flow test kit for detecting a high molecular weight substance
Publication Date: 2017.08.16 CHARM SCIENCES INC
  • EP2715358B1 patent drawingFigure 1
  • EP2715358B1 patent drawingFigure 2
  • EP2715358B1 patent drawingFigure 3

AI summary

Label complexes, lateral flow apparatus and methods of detecting a high molecular weight substance are shown and described. In one embodiment, the label complex includes an antispecies antibody and another antibody having sensitivity to both the antispecies antibody and to a control line capture agent, an antibody binding protein and a detectable component. Typically, the antibody binding protein may bind to a receptor for the analyte or to the anti-species antibody. In yet other embodiments, a lateral flow test strip includes the label complex and a solid support that traverses lateral flow of a liquid sample and provides a detectable signal.