Cell Analysis Apparatus Fluorescence Waveform Differentiation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing cell analysis methods face challenges in accurately distinguishing between aggregating cells and non-aggregating cells due to unclear signal waveforms from forward-scattered light, which affects the accuracy of cell size and shape measurements.

Innovation Solution

A cell analysis apparatus and method that uses fluorescence signals from stained nuclei to determine the height and length of waveforms, allowing for the differentiation between aggregating and non-aggregating cells by calculating a ratio of difference integration value to peak value, enabling precise classification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If forward-scattered light is used to distinguish aggregating cells from non-aggregating cells, then cell differentiation is possible, but signal waveform clarity deteriorates due to height variations and flow direction effects

Engineering Contradiction:
Improvecell differentiation accuracyVSAvoidsignal waveform clarity
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The invention changes the detection parameter from forward-scattered light to fluorescence signal. By using fluorescence emission from stained cell nuclei instead of light scattering, the signal waveform clarity is significantly improved, eliminating the problems of height variations and ambiguous peaks/troughs that occurred with forward-scattered light detection.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the optical scattering detection mechanism with fluorescence detection mechanism. Instead of measuring how cells scatter incident light (mechanical/optical interaction), the system uses fluorescent stains that emit light when excited, providing clearer signal waveforms that accurately reflect cell aggregation states.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If cells are arranged in one straight line using sheath flow cell, then simultaneous passage of multiple cells is suppressed, but cell aggregation still occurs affecting measurement accuracy

Engineering Contradiction:
Improvecell size and shape measurementVSAvoidcell distribution uniformity
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The invention uses fluorescent staining as an intermediary to mark cell nuclei, which then emits fluorescence signals that can clearly distinguish individual cells even when aggregated. The fluorescence signal acts as a mediator that provides unambiguous information about cell presence and aggregation state, overcoming the limitations of scattered light detection.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If fluorescence signal waveform analysis is performed to distinguish aggregating cells, then differentiation accuracy is improved, but signal processing complexity increases

Engineering Contradiction:
Improveaggregating cell differentiationVSAvoidsignal processing complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts the key distinguishing feature by analyzing the presence or absence of troughs in the fluorescence signal waveform. This extraction of the critical waveform characteristic (trough detection) provides a simple binary classification method that clearly distinguishes aggregating cells from non-aggregating cells without requiring complex analysis algorithms.

Inventive Principle:
Principle #2Taking out (Extraction)

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 provides clear and accurate differentiation between aggregating and non-aggregating cells, improving measurement accuracy and reducing noise, thereby enhancing the detection of cancer and atypical cells.

Implementation Method 1

irradiating the measurement sample flowing in the flow cell with laser beam, and detecting fluorescence from the nucleus of the cell in the measurement sample

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2204643B1Cell analysis apparatus and cell analysis method
Publication Date: 2019.08.21 SYSMEX CORP
  • EP2204643B1 patent drawingFigure 1
  • EP2204643B1 patent drawingFigure 2
  • EP2204643B1 patent drawingFigure 3

AI summary

A cell analysis apparatus that can accurately distinguish between an aggregating cell and a non-aggregating cell is provided. The cell analysis apparatus (10) includes: an optical detection section (3) for flowing a measurement sample obtained from a biological sample and a pigment into a flow cell (51), irradiating the measurement sample flowing in the flow cell (51) with laser beam and detecting fluorescence from the measurement sample; a signal processing circuit (4) for acquiring, based on a fluorescence signal outputted from the detection section (3), a value reflecting the height of a waveform of the signal and a value reflecting the length of a ridge line of the waveform of the signal; and a system control section (13) for distinguishing between an aggregating cell formed by aggrefation of a plurarity of cells and a non-aggregating cell, based on the value reflecting the height of the waveform of the fluorescence signal and the value reflecting the length of the ridge line of the waveform of the fluorescence signal obtaind by the signal processing circuit (4).