Cell Identification via Fluorescence and White Light Imaging

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Solution Overview

Problem

Current methods for identifying rare cells in blood samples, such as circulating tumor cells and fetal nucleated red blood cells, suffer from low accuracy due to the low ratio of target cells to background cells and suboptimal binding rates of antibodies.

Innovation Solution

A cell identification method utilizing fluorescent markers to differentiate target cells from non-target cells through fluorescence scanning and subsequent white light imaging to confirm cell phenotype and shape, achieving high accuracy in rare cell identification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If blood smears with chemical staining are used to identify rare cells, then the identification process is simple and fast, but the identification accuracy is low due to the low ratio of target cells to background cells

Engineering Contradiction:
Improveidentification accuracyVSAvoididentification process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses fluorescent markers that emit different colors/wavelengths of light when excited, allowing target cells to be distinguished from background cells through fluorescence imaging. The fluorescent markers bind specifically to target cells, causing them to glow under fluorescent microscopy, which dramatically improves detection sensitivity and accuracy compared to conventional chemical staining.

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent introduces fluorescent markers as intermediary substances that mediate between the target cells and the detection system. These markers bind to specific antigens or structures on target cells, converting biological specificity into optical signals that can be detected and quantified, thereby resolving the contradiction between simple detection and high accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If antibody-based fluorescent markers are used to mark target cells, then the specificity of target cell identification is improved, but the binding rate of antibodies is suboptimal leading to reduced identification accuracy

Engineering Contradiction:
Improveidentification accuracyVSAvoidantibody binding rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent employs composite fluorescent markers consisting of antibodies conjugated to fluorescent dyes. This composite structure combines the specific binding capability of antibodies with the detectable optical signal of fluorescent markers, achieving both high specificity and high detection accuracy. The composite material approach overcomes the limitation of suboptimal antibody binding by enhancing the signal-to-noise ratio through fluorescent amplification.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent optimizes various parameters including antibody concentration, incubation time, temperature, and pH conditions to maximize antibody binding efficiency. By systematically adjusting these parameters, the patent achieves optimal binding rates that improve identification accuracy while maintaining the specificity of antibody-target cell interactions.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If multiple fluorescent markers with different wavebands are used to differentiate target cells from non-target cells, then the identification accuracy is significantly improved, but the device complexity and analysis time increase

Engineering Contradiction:
Improveidentification accuracyVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the detection process into distinct fluorescent channels, each optimized for detecting specific markers. By dividing the complex multi-parameter detection into separate wavelength-specific channels, the system can simultaneously analyze multiple markers without overwhelming the detection system, thereby reducing analysis time while maintaining high identification accuracy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary co-staining of cells with multiple fluorescent markers before imaging, allowing simultaneous detection of multiple cell characteristics. This preliminary action eliminates the need for sequential staining and imaging steps, significantly reducing analysis time while preserving the ability to differentiate target cells from non-target cells with high accuracy.

Inventive Principle:
Principle #10Preliminary action

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 significantly enhances the accurate identification of rare cells by leveraging the specificity of fluorescent markers and the precision of white light imaging, thereby improving clinical diagnostics and research applications.

Implementation Method 1

fluorescent markers include a first fluorescent marker for marking nuclei, a second fluorescent marker for marking the target cells, and a third fluorescent marker for marking the target cells or the non-target cells

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

A fluorescence scan is performed on the analysis sample respectively with a first fluorescence waveband corresponding to the first fluorescent marker, a second fluorescence waveband corresponding to the second fluorescent marker, and a third fluorescence waveband corresponding to the third fluorescent marker

Methodology Applied
Scientific EffectFluorescence excitation: Fluorescence

Data Source

PatentEP4564006A1Cell identification method
Publication Date: 2025.06.04 TSENG FAN GANG
  • EP4564006A1 patent drawingFigure 1
  • EP4564006A1 patent drawingFigure 2
  • EP4564006A1 patent drawingFigure 3

AI summary

Provided are a cell identification method for identifying target cells by combining the results of fluorescence intensity analysis, fluorescence image analysis, and white light image analysis.