Scanning Molecule Counting for Low Concentration Particle Detection
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Solution Overview
Problem
Conventional optical analysis technologies, such as FCS and FIDA, struggle with detecting target particles at low concentrations due to the need for statistical processing of fluorescence intensity fluctuations, which becomes inaccurate when particles rarely enter the microregion, requiring higher concentrations and longer measurement times.
Innovation Solution
A scanning molecule counting method that uses a luminescent probe bound to target particles, allowing for their detection by moving a photodetection region and counting bound particles individually, even at low concentrations, by exploiting differences in luminescence properties between bound and unbound states.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional optical analysis technologies (FCS, FIDA) are used to detect target particles, then measurement can be performed with extremely low concentration samples and small sample amounts, but detection accuracy deteriorates when particle concentration is too low causing particles to rarely enter the microregion
Solution Approach 1:
The patent introduces a luminescent probe as an intermediary substance that binds to target particles to form particle-probe complexes. This mediator enhances the detectability of target particles by providing a luminescence signal that can be detected even when particles are present at very low concentrations, thus resolving the contradiction between low sample concentration and detection accuracy
Solution Approach 2:
The patent changes the detection parameter from direct particle detection to detection of luminescence properties. By measuring the luminescence intensity and characteristics of particle-probe complexes rather than relying on particle presence alone, the system achieves accurate detection even at low particle concentrations, resolving the contradiction between quantity and measurement precision
2Quantity of substance
If conventional statistical processing of fluorescence intensity fluctuations is used, then detection can be performed in a microregion, but measurement time increases when particles rarely enter the microregion requiring longer observation periods
Solution Approach 1:
The patent replaces the statistical processing mechanism with a direct counting mechanism. Instead of analyzing fluorescence intensity fluctuations over time, the system directly counts individual particle-probe complexes as they pass through the detection region, dramatically reducing measurement time while maintaining accuracy even at low particle concentrations
Solution Approach 2:
The patent creates a luminescence signal copy of the target particle by binding a luminescent probe to it. This luminescence copy provides a detectable signal that allows direct observation and counting of particles without requiring prolonged statistical analysis, thus reducing measurement time while maintaining detection sensitivity
3Measurement precision
If luminescent probe binding is used to enhance detection sensitivity, then detection at lower concentrations becomes possible, but device complexity increases due to additional binding steps and luminescence property analysis
Solution Approach 1:
The patent designs the luminescent probe to serve multiple functions: it binds specifically to target particles, provides a detectable luminescence signal, and enables both qualitative detection and quantitative counting. This multi-functionality reduces the need for separate detection systems and simplifies the overall device complexity while maintaining high detection sensitivity
Solution Approach 2:
The patent utilizes luminescence property changes (analogous to color changes) as a simple, direct detection method. By measuring the luminescence intensity and characteristics of particle-probe complexes, the system achieves high detection sensitivity without requiring complex analytical equipment, thus resolving the contradiction between sensitivity and device complexity
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 target particles at lower concentrations and in shorter measurement times by enhancing particle concentration prior to measurement, allowing for accurate quantitation of particle number density without statistical processing of fluorescence fluctuations.
Implementation Method 1
a luminescent probe that binds to the target particle, wherein luminescence properties of released light differ between a state in which the luminescent probe is bound to the target particle and a state in which the luminescent probe is present alone
Data Source
Figure 1A~1B
Figure 1C~2B
Figure 3A~4B
AI summary
Provided is a method for detecting a target particle, having (a) a step for concentrating a test sample so as to enhance the concentration of target particles in the test sample, (b) a step for preparing a sample solution containing the test sample concentrated in step (a) and a luminescent probe that binds to the target particle, and allowing the target particle and the luminescent probe to bind in the sample solution, and (c) a step for counting the number of target particles bound to the luminescent probe present in the sample solution according to a scanning molecule counting method, wherein the luminescence properties of the released light differ between the state in which the luminescent probe is bound to the target particle and the state in which the luminescent probe is present alone.