Single Particle Detection via Light Intensity Reduction

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Solution Overview

Problem

Current single particle detection techniques using optical systems like confocal microscopes struggle to detect non-light-emitting particles or those with low light intensity, as they are prone to errors from stray light and Raman scattering, and require labeling which can denature the particles, limiting their concentration detection capabilities.

Innovation Solution

A single particle detection device that moves a light detection region within a sample solution, detecting a reduction in background light intensity as a signal for individual particles, allowing for the detection of non-light-emitting particles without labeling, by utilizing a confocal or multiphoton microscope with a mechanism to move the light detection region and process time series light intensity data to identify particle presence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescent labeling is used to detect single particles, then detection sensitivity is improved, but particle denaturation and loss of native state occur

Engineering Contradiction:

Improvedetection sensitivityVSAvoidparticle native state

Core Design Contradiction:

Measurement precisionVSStability of the object's composition

Solution Approach 1:

The invention extracts the detection target from light-emitting particles to non-light-emitting particles by detecting the absence or reduction of light (shadow effect) rather than presence of light, thereby eliminating the need for fluorescent labeling and preserving the native state of particles

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of detecting light emitted by labeled particles, the invention inverts the approach by detecting the reduction or absence of light when non-labeled particles pass through the confocal volume, thereby detecting particles without labeling that would cause denaturation

Inventive Principle:

Principle #13The other way round (Inversion)

2Quantity of substance

If statistical analysis methods (FCS, FIDA) are used to detect particles, then concentration information can be obtained, but detection reliability deteriorates at low particle concentrations due to statistical fluctuations

Engineering Contradiction:

Improveconcentration informationVSAvoiddetection reliability

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The invention replaces statistical mechanical analysis methods (FCS, FIDA) with direct event counting of individual particle passages through the confocal volume, eliminating statistical fluctuations and enabling reliable detection even at very low concentrations where traditional methods fail

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Difficulty of detecting and measuring

If conventional light detection is used in solutions with light-emitting substances, then detection capability is improved, but measurement precision deteriorates due to stray light and Raman scattering errors

Engineering Contradiction:

Improvedetection capabilityVSAvoidmeasurement accuracy

Core Design Contradiction:

Difficulty of detecting and measuringVSMeasurement precision

Solution Approach 1:

The invention converts the harmful effect of light-emitting substances (stray light, Raman scattering) into a beneficial reference signal by using them as a background light source, where particle passages are detected as reductions or absences of this background light, thereby eliminating interference from the light-emitting substances

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 of single particles at lower concentrations without statistical fluctuations, reducing errors from stray light and Raman scattering, and eliminating the need for labeling, thus improving the accuracy and applicability of particle concentration analysis.

Implementation Method 1

by using an optical system of a confocal microscope or a multiphoton microscope, which can detect light from a micro region in a solution

Methodology Applied

Scientific EffectConfocal microscopy: Focusing

Implementation Method 2

the light from the light detection region includes substantially constant background light; and the signal indicating an existence of each single particle is a reduction of the light intensity detected with the light detector, which reduction occurs when the single particle enters into the light detection region

Methodology Applied

Scientific EffectLight absorption: Absorption (EM radiation)

Data Source

PatentUS9488578B2Single particle detection device, single particle detection method, and computer program for single particle detection, using optical analysis

Publication Date: 2016.11.08 OLYMPUS CORPORATION(JP)

AI summary

There is provided a single particle detection technique based on a scanning molecule counting method, enabling individual detection of a single particle using light measurement with a confocal or multiphoton microscope, and quantitative observation of conditions or characteristics of the particle. The inventive technique of detecting a single particle in a sample solution detects light containing substantially constant background light from a light detection region with moving the position of the light detection region of the microscope in a sample solution to generate time series light intensity data; and detects individually a light intensity reduction occurred when a single particle which does not emit light (or a particle whose emitting light intensity in a detected wavelength band is lower than the background light) enters in the light detection region in the time series light intensity data as a signal indicating the existence of each single particle.