Cell Selection Using Dual-Wavelength Fluorescence for Genomic Detection

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Solution Overview

Problem

In situ hybridization methods often result in poorly stained cells and nonspecific probe binding, which complicates the accurate detection of abnormal cells, as these cells can interfere with the analysis and lead to incorrect identification of genomic abnormalities.

Innovation Solution

A cell selection method using fluorescent dyes that emit different wavelengths for staining nucleic acids and hybridization with evaluation probes, allowing for the selection of analysis target cells based on fluorescence intensity and brightness, thereby excluding poorly stained cells and detecting abnormal cells with genomic abnormalities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If in situ hybridization is performed to detect abnormal cells, then genomic abnormalities can be identified, but poorly stained cells and nonspecific probe binding occur which reduce detection accuracy

Engineering Contradiction:
Improvedetection accuracyVSAvoidstaining quality
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent segments the detection process into two distinct stages: first, quality control through evaluation probe hybridization to identify properly stained cells; second, actual detection using detection probes on the selected subset. This segmentation separates quality assurance from detection, eliminating the interference of poorly stained cells from the analysis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary action by conducting evaluation probe hybridization and cell selection before the actual detection process. Cells are pre-screened based on their staining quality using evaluation probes, and only cells meeting the quality criteria are selected for subsequent detection with detection probes, ensuring high-quality input for the detection stage.

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If all cells are analyzed for genomic abnormalities, then detection coverage is maximized, but poorly stained cells interfere with accurate detection

Engineering Contradiction:
Improveabnormal cell detection accuracyVSAvoidinterference from poorly stained cells
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and removes poorly stained cells from the analysis pool through a selection process. By using evaluation probes to identify and select only properly stained cells, the harmful factor of poor staining is extracted away from the detection process, allowing accurate analysis of genomic abnormalities without interference.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the potential harm of having poorly stained cells in the sample into a benefit by using the evaluation probe hybridization as a quality control mechanism. The presence of evaluation targets allows the system to identify and select only high-quality cells, turning what could be a source of error into a means of ensuring detection accuracy.

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

3Adaptability or versatility

If fluorescent dyes with different wavelengths are used for nucleic acid staining and probe hybridization, then cell selection based on fluorescence intensity is enabled, but the system complexity increases

Engineering Contradiction:
Improvecell selection capabilityVSAvoidfluorescence detection system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies multi-functionality by using the fluorescence detection system to perform two distinct functions: first, quality control through evaluation of nucleic acid staining intensity; second, detection of probe hybridization signals. The same fluorescence detection apparatus handles both evaluation and detection tasks, reducing the need for separate systems while enabling comprehensive cell selection and analysis.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 approach enables accurate detection of abnormal cells by distinguishing between appropriately stained and unstained cells, improving the specificity and sensitivity of genomic abnormality detection, such as gene amplification, deletion, inversion, and translocation.

Implementation Method 1

a first fluorescent dye that emits fluorescence having a first wavelength

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

an evaluation probe including a second fluorescent dye that emits fluorescence having a second wavelength different from the first wavelength

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

a light receiving step of applying light to the sample and receiving fluorescence from the first fluorescent dye and fluorescence from the second fluorescent dye

Methodology Applied
Scientific EffectFluorescence excitation: Fluorescence

Data Source

PatentUS11060134B2Cell selection method, cell detection method, cell selection apparatus, and cell detection apparatus
Publication Date: 2021.07.13 SYSMEX CORP
  • US11060134B2 patent drawing
  • US11060134B2 patent drawing
  • US11060134B2 patent drawing

AI summary

Disclosed is a cell selection method including a sample preparation step of preparing a sample by performing staining of nucleic acid in each of cells by a first fluorescent dye; and hybridization with respect to an evaluation target region in DNA in each cell by an evaluation probe including a second fluorescent dye; a light receiving step of applying light to the sample and receiving fluorescence from the first fluorescent dye and fluorescence from the second fluorescent dye; and a selection step of selecting an analysis target cell on the basis of intensity of the fluorescence from the first fluorescent dye and intensity of the fluorescence from the second fluorescent dye, wherein the first fluorescent dye is a dye that emits fluorescence having a first wavelength, and the second fluorescent dye is a dye that emits fluorescence having a second wavelength different from the first wavelength.