Scanning Molecular Counting for Low Concentration Particle Quantification

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Solution Overview

Problem

Current methods for detecting and quantifying low concentrations of particles in sample solutions, such as those used in biological research, require large sample volumes and lengthy measurement times, making them inefficient for rare or expensive samples and clinical diagnostics.

Innovation Solution

A scanning molecular counting method using a confocal or multiphoton microscope to detect and count luminescent probes bound to target particles, allowing for the calculation of particle concentration based on a calibration curve, enabling sensitive detection and quantification of particles even at low concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional photometric measurement techniques are used to detect particles in sample solutions, then measurement sensitivity can be improved, but sample volume and measurement time increase significantly

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

Solution Approach 1:

The patent segments the sample solution into multiple regions and performs parallel photometric measurements on each region simultaneously using an array of photodetectors. This allows the entire sample to be analyzed in one measurement cycle rather than sequentially, dramatically reducing measurement time while maintaining detection sensitivity through multi-point concurrent analysis

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent transitions from one-dimensional sequential scanning measurement to two-dimensional parallel array measurement by arranging multiple photodetectors in an array configuration. This dimensional change enables simultaneous detection across multiple spatial positions, reducing measurement time while preserving measurement precision through increased spatial sampling

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

2Measurement precision

If conventional photometric measurement techniques are used to detect particles in sample solutions, then measurement sensitivity can be improved, but the required sample volume increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsample volume
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent segments the detection process into multiple parallel photodetector channels, each analyzing a small portion of the sample simultaneously. This segmentation allows the system to achieve high detection sensitivity through collective analysis of multiple small-volume measurements rather than requiring a large single-volume measurement, thereby reducing the total sample volume needed

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses multiple photodetectors to perform partial measurements on different regions of the sample in parallel. Each photodetector performs a limited measurement on a small sample portion, but the cumulative effect of all partial measurements achieves high detection sensitivity while requiring minimal total sample volume

Inventive Principle:
Principle #16Partial or excessive action

3Productivity

If scanning molecular counting method is used to detect low concentration particles, then measurement speed and sample efficiency are improved, but detection precision may be compromised at extremely low concentrations

Engineering Contradiction:
Improvemeasurement speedVSAvoiddetection accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary concentration of target particles in the sample solution before photometric measurement, or uses preliminary selection of optimal measurement parameters based on expected concentration ranges. This preliminary action ensures that even extremely low concentration particles can be detected with high precision during the rapid scanning measurement process

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements feedback mechanisms where measurement results from initial scanning are used to adjust subsequent measurement parameters, such as photodetector sensitivity settings, integration time, or scanning resolution. This feedback loop maintains high detection accuracy for low concentration particles while preserving the overall speed advantage of the scanning method

Inventive Principle:
Principle #23Feedback

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 precise detection and quantification of particles at extremely low concentrations with minimal sample volume and reduced measurement time, enhancing the efficiency of biological research and clinical diagnostics.

Implementation Method 1

detecting light signals emitted from the luminescent probe in the light detection region

Methodology Applied
Scientific EffectLuminescence: Luminescence

Implementation Method 2

detecting light from a micro region in a solution such as an optical system of a confocal microscope or a multiphoton microscope

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

an optical system of a laser confocal microscope

Methodology Applied
Scientific EffectLaser: Laser

Implementation Method 4

the focal region to which the laser light of the microscope is condensed, called a confocal volume

Methodology Applied
Scientific EffectFocusing: Focusing

Implementation Method 5

the measurement is performed on the fluorescence intensity from fluorescence molecules or fluorescently labeled molecules

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9116127B2Quantitative determination method for target particles, photometric analysis device, and computer program for photometric analysis
Publication Date: 2015.08.25 OLYMPUS CORPORATION(JP)
  • US9116127B2 patent drawing
  • US9116127B2 patent drawing
  • US9116127B2 patent drawing

AI summary

The method of the present invention includes: preparing a sample solution containing the target particles and luminescent probes to be bound to the target particles, and binding these in the sample solution; moving a position of a light detection region of the optical system in the sample solution using a confocal microscope or a multiphoton microscope, and detecting light signal emitted from the luminescent probe in the light detection region while moving the position of the light detection region, and individually detecting the target particles directly or indirectly; and counting the number of the detected target particles, and calculating the concentration of the target particles in the sample solution from the number of the counted target particles on the basis of a calibration curve that approximates the correlation between the concentration or quantity of the target particles in the sample solution and the number of the target particles.