Single Particle Detection via Light Intensity Variation
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Solution Overview
Problem
Current optical systems used in single particle detection, such as confocal microscopes, face challenges in distinguishing between light-emitting and non-light-emitting particles when they have different intensities relative to the background light, making it difficult to detect non-light-emitting particles at low concentrations.
Innovation Solution
A single particle detection device that uses a confocal microscope or multiphoton microscope with a light detection region mover and signal processor to differentiate between light-emitting and non-light-emitting particles by detecting changes in light intensity, where light-emitting particles cause an increase and non-light-emitting particles cause a decrease in light intensity within the detection region, allowing for simultaneous detection and identification of both types of particles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional optical analysis techniques (FCS, FIDA) are used to detect particles in solution, then statistical calculation processes can be performed on light intensity data, but the detection limit is restricted and cannot detect particles at lower concentrations
Solution Approach 1:
The patent inverts the conventional detection approach by moving the light detection region through the sample solution instead of keeping the detection region stationary and measuring statistical fluctuations. This scanning approach allows individual particle detection by recording light intensity changes over time as particles pass through the detection region, enabling detection at much lower concentrations than conventional statistical methods
Solution Approach 2:
The patent replaces the statistical calculation mechanism with a direct temporal measurement approach. Instead of analyzing statistical properties of continuously detected light, the system uses a scanning mechanism that records light intensity variations over time, where each particle passage creates a distinct signal that can be individually identified and counted
2Measurement precision
If the light detection region is moved in the sample solution to scan and detect individual particles, then particle counting and concentration measurement become possible at lower concentrations, but the ability to distinguish between light-emitting and non-light-emitting particles with different intensities becomes difficult
Solution Approach 1:
The patent changes the detection parameter from static light intensity to dynamic light intensity variation over time. By analyzing the temporal profile of light intensity changes as particles pass through the scanning detection region, the system can distinguish between different particle types based on their characteristic signal patterns, even when their absolute light intensities differ
Solution Approach 2:
The patent implements signal processing that provides feedback on light intensity variations. The system continuously monitors light intensity changes during scanning and uses this feedback to identify and classify particles based on their characteristic signals, enabling differentiation between light-emitting and non-light-emitting particles
3Quantity of substance
If statistical calculation processes are performed on light intensity data from continuously measuring fluorescence molecules, then concentration and characteristics can be detected, but the measurement requires larger sample amounts and longer measuring times
Solution Approach 1:
The patent performs preliminary action by moving the light detection region through the sample solution before performing any particle detection or analysis. This scanning approach pre-positions the detection capability to encounter particles individually, eliminating the need for statistical accumulation over large sample volumes and long measurement times required by conventional methods
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 both light-emitting and non-light-emitting particles in the same solution, even at low concentrations, improving the accuracy and efficiency of particle analysis in biological and medical research.
Implementation Method 1
detecting light from a micro region in a sample solution... measuring with an optical system as described above a light intensity variation because of an existence of a single particle
Data Source
AI summary
There is provided a single particle detection technique based on the scanning molecule counting method which individually detects single particles using light measurement with a confocal or multiphoton microscope, where the existences of a non-light-emitting particle and a light-emitting particle can be detected while being discriminated from one another in a sample solution. The inventive technique of detecting a single particle detects light from a light detection region during moving the position of the light detection region of the microscope in a sample solution containing a non-light-emitting particle and a light-emitting particle to generate time series light intensity data; and detects in the time series light intensity data a light intensity increase relative to background light intensity as a signal indicating the existence of the light-emitting particle and a light intensity reduction relative to the background light intensity as a signal indicating the existence of the non-light-emitting particle.