Scanning Molecule Counting for Low-Concentration Particle Detection

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Solution Overview

Problem

Current optical measurement technologies require high concentrations of target particles in a sample solution for accurate detection, making it difficult to analyze scarce or expensive samples effectively, especially when the concentration of particles is low.

Innovation Solution

The scanning molecule counting method uses a luminescent probe bound to target particles, allowing for the detection of individual particles through light detection with a confocal microscope or multi-photon microscope, enabling the measurement of low-concentration particles by forming a complex and performing solid-liquid separation treatment to isolate and count the particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional optical measurement technology is used, then measurement accuracy is maintained, but the target particle concentration must be high

Engineering Contradiction:
Improvedetection accuracyVSAvoidtarget particle concentration
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent introduces a luminescent probe as an intermediary substance that binds to target particles. This probe acts as a mediator between the target particle and the detection system, converting the detection problem from directly detecting faint light from particles to detecting bright luminescence from probes, thereby enabling accurate detection at low concentrations

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the optical parameters of the target particles by attaching luminescent probes with high quantum yield. This transforms the detection parameter from relying on intrinsic particle light emission to detecting probe luminescence intensity, allowing detection sensitivity to function at much lower particle concentrations

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If conventional optical measurement is used, then detection is possible, but sample amount and measurement time are large

Engineering Contradiction:
Improvedetection capabilityVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The luminescent probe serves as a signal amplifier that produces strong luminescence signals even from single particles. This intermediary enables the detection system to achieve high signal-to-noise ratios with minimal integration time, dramatically reducing measurement duration while maintaining detection accuracy

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces conventional mechanical scanning or flow-based detection methods with a stationary confocal detection system that uses optical sectioning. This substitution eliminates the need for mechanical movement or large sample volumes, enabling rapid measurement of minute samples

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

3Device complexity

If conventional optical measurement is used, then equipment is simple, but detection sensitivity is insufficient for low concentration particles

Engineering Contradiction:
Improvesystem simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The luminescent probe acts as a signal transducer that converts the detection task from directly observing faint particle light to detecting intense probe luminescence. This intermediary approach maintains relative system simplicity while achieving ultra-sensitive detection capabilities through the probe's high quantum yield and specific binding to target particles

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs confocal optical sectioning to create a localized detection volume with high spatial resolution. This local quality enhancement concentrates the detection sensitivity in a specific three-dimensional region, enabling sensitive detection of individual particles or complexes without requiring complex whole-sample analysis systems

Inventive Principle:
Principle #3Local quality

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 method allows for the accurate detection and quantification of target particles at extremely low concentrations, reducing the sample amount required and measurement time, enhancing the efficiency and accuracy of biochemical analyses.

Implementation Method 1

uses a luminescent probe bound to target particles, allowing for the detection of individual particles through light detection

Methodology Applied
Scientific EffectLuminescence: Luminescence

Implementation Method 2

optical system of a confocal microscope and multi-photon microscope capable of detecting light from a microregion in the solution

Methodology Applied
Scientific EffectConfocal microscopy: Focusing

Implementation Method 3

ultra-high-sensitivity photodetection technology capable of performing photon counting (detecting individual photons)

Methodology Applied
Scientific EffectPhoton counting: Photoelectric Effect

Implementation Method 4

a particle for separation and recovery that is capable to be bound to a complex composed of the target particle and the luminescent probe

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS9841418B2Method for detecting target particle
Publication Date: 2017.12.12 OLYMPUS CORPORATION(JP)
  • US9841418B2 patent drawing
  • US9841418B2 patent drawing
  • US9841418B2 patent drawing

AI summary

This method for detecting a target particle comprises (a) preparing a solution containing a target particle, a luminescent probe that binds to the target particle and a particle for separation and recovery, or containing the target particle bound to the luminescent probe, the luminescent probe and the particle for separation and recovery, and forming a complex composed of the target particle, the luminescent probe and the particle for separation and recovery in the solution, (b) recovering the particle for separation and recovery from the solution by solid-liquid separation treatment after the (a) and preparing a sample solution containing the particle for separation and recovery, and (c) calculating the number of the complex present in the sample solution according to a scanning molecule counting method, wherein the particles for separation and recovery bind to a complex composed of the target particles and the luminescent probe.