Digital Chromatographic Assay System for Ultra-Sensitive Analyte Detection

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Solution Overview

Problem

Current digital assay methods for analyte detection are cumbersome, time-consuming, and difficult to industrialize, limiting their suitability for on-site and rapid detection, and they struggle with achieving ultra-sensitive detection due to complex procedures and sensitivity restrictions.

Innovation Solution

An ultra-sensitive digital rapid chromatographic assay system combining a chromatography reaction system, an optical imaging system, and an image processing system, featuring a lateral or vertical flow chromatographic reaction system with immobilized capture biological ligands and tracer nanoparticles, and utilizing fluorescence or dark-field microscopy for single nanoparticle visualization and counting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If digital PCR or digital ELISA methods are used to achieve ultra-sensitive detection, then detection sensitivity is improved, but device complexity and ease of operation deteriorate due to complicated procedures and difficult standardization

Engineering Contradiction:
Improvedetection sensitivityVSAvoidprocedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent divides the sample into millions of femtoliter-sized microwells, distributing target molecules across micro-reaction units. This segmentation enables digital reading of single molecule signals while maintaining operational simplicity through automated processing.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces magnetic beads as intermediaries to capture and concentrate target analytes before detection. This intermediary step simplifies the detection procedure by pre-concentrating targets, thereby improving sensitivity without significantly increasing operational complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If single nanoparticle counting methods are used to achieve ultra-trace detection, then detection sensitivity is improved, but productivity deteriorates due to time-consuming procedures

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent performs preliminary concentration of target analytes using magnetic beads before the actual detection step. This preliminary action reduces the time required for single nanoparticle counting by pre-enriching targets, thereby improving productivity without sacrificing detection sensitivity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces manual single nanoparticle counting with automated optical detection systems that can rapidly image and count particles. This substitution of mechanical/manual operations with automated systems significantly improves detection speed while maintaining sensitivity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Ease of operation

If traditional immunoassays are used for analyte detection, then ease of operation is maintained, but measurement precision deteriorates due to inability to detect ultra-trace signals

Engineering Contradiction:
Improveoperational simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent transitions from detecting macroscopic overall signals to detecting single particle signals at the microscopic level. This dimensional change from bulk to single-particle detection enables ultra-trace sensitivity while maintaining operational simplicity through standardized protocols.

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

Solution Approach 2:

The patent changes the detection parameter from macroscopic signal intensity to single particle count. This parameter change enables detection of ultra-trace analytes while maintaining ease of operation through automated counting systems that simplify data interpretation.

Inventive Principle:
Principle #35Parameter changes

4Ease of operation

If macroscopic overall signal collection is used in immunochromatography, then ease of operation is maintained, but measurement precision deteriorates due to inability to recognize single particle signals

Engineering Contradiction:
Improvedetection simplicityVSAvoidsignal detection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent transitions from collecting macroscopic overall signals to visualizing and counting individual particles at the microscopic level. This dimensional change enables recognition of single particle signals while maintaining operational simplicity through standardized imaging and counting procedures.

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 system significantly enhances detection sensitivity, simplifies procedures, reduces detection time, and facilitates easy standardization, enabling fast, cost-effective, and industrializable on-site detection of analytes, improving upon traditional methods by allowing single particle counting and microscopic signal amplification.

Implementation Method 1

The optical imaging system is a fluorescence microscopy amplification or dark-field microscopy amplification optical system, which can visualize a single tracer nanoparticle specifically bound on the reaction membrane of the chromatography reaction system

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

The optical imaging system is a fluorescence microscopy amplification or dark-field microscopy amplification optical system, which can visualize a single tracer nanoparticle specifically bound on the reaction membrane of the chromatography reaction system

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 3

The chromatography reaction system is a lateral flow or vertical flow chromatographic reaction system

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 4

a detection area on the reaction membrane of the chromatography reaction system is immobilized with capture biological ligands, and the analytes to be detected is specifically captured and enriched by means of the biological ligands

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS20230305001A1Ultra-sensitive digital rapid chromatographic assay system and method for analytes detection
Publication Date: 2023.09.28 SHANGHAI DERMATOLOGY HOSPITAL
  • US20230305001A1 patent drawing
  • US20230305001A1 patent drawing
  • US20230305001A1 patent drawing

AI summary

An ultra-sensitive digital rapid chromatographic assay system includes a chromatography system, an optical imaging system, and an image processing system. The chromatography system is a lateral flow or vertical flow chromatography system. The detection area on a reaction membrane of the chromatography system is immobilized with capture biological ligands, the analytes to be detected is specifically enriched by means of the captured biological ligands, and the analytes enriched in the detection area is specifically recognized by the detection biological ligands labelled with tracer nanoparticles. The optical imaging system can visualize a single tracer nanoparticle specifically bound on the reaction membrane. The image processing system includes a detection area recognition module and a nanoparticle counting module, and the counted number of tracer nanoparticles specifically binding to the detection area and the concentration of the analytes to be detected are a proportional relationship.