Antigen Detection via Antibody Supports for Sub-Nanomolar Sensitivity

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Solution Overview

Problem

Conventional methods for detecting pathogen proteins in human biological samples are incapable of detecting sub-nanomolar levels, which is critical for accurate infection diagnosis.

Innovation Solution

A method involving enzyme-digested biological samples contacted with antibody-modified solid supports (AMSS) under specific conditions, followed by mass spectrometry-based techniques to detect and identify disease-specific biomarkers, including disease-specific antigens, proteins, or peptides, with a concentration range of 0.1 pM to 6 μM, using techniques like MALDI-TOF MS and tandem mass spectrometry for precise identification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional detection methods are used, then the detection process is simple, but the detection sensitivity is insufficient and cannot detect sub-nanomolar levels

Engineering Contradiction:

Improvedetection sensitivityVSAvoiddetection system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The detection system is segmented into distinct functional modules: antibody-modified solid supports for specific binding, mass spectrometry for detection, and enzyme digestion for sample preparation. This segmentation allows each component to be optimized independently, achieving sub-nanomolar detection sensitivity while maintaining manageable system complexity through modular design

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Antibody-modified solid supports serve as intermediary elements between the biological sample and the mass spectrometry detector. These supports specifically bind to pathogen proteins, enriching them from the complex biological matrix and enabling sensitive detection at sub-nanomolar levels that would be impossible with direct detection methods

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If higher detection sensitivity is achieved, then accurate infection diagnosis becomes possible, but the detection method becomes more complex

Engineering Contradiction:

Improvediagnosis accuracyVSAvoiddetection method complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The method performs preliminary actions by using antibody-modified solid supports to capture and enrich pathogen proteins before mass spectrometry analysis. This pre-concentration step is critical for achieving accurate diagnosis at sub-nanomolar levels, as it prepares the sample in advance and reduces the complexity of the subsequent detection process

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The system changes key parameters including the use of specific antibody-antigen binding interactions, mass-to-charge ratio filtering, and enzymatic digestion conditions to optimize detection sensitivity. These parameter changes enable reliable diagnosis accuracy while maintaining methodological clarity and reducing overall complexity

Inventive Principle:

Principle #35Parameter changes

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 the detection and identification of disease-specific biomarkers at sub-nanomolar levels, allowing for accurate diagnosis of infections caused by pathogens such as bacteria, fungi, or viruses, including tuberculosis and HIV, with high sensitivity and specificity.

Implementation Method 1

contacting an enzyme-digested biological sample with an antibody-modified solid support (AMSS) under conditions that promote binding of the AMSS to its target if present in the contacted biological sample, wherein the antibodies bind specifically to a disease-specific biomarker

Methodology Applied

Scientific EffectAntibody-antigen binding: