Flow Cytometry Cell Clustering for Reproducible Anomaly Detection
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Solution Overview
Problem
Conventional hematology analyzers are laborious, time-consuming, and dependent on operator expertise, lacking reproducibility and efficiency in analyzing biological samples, particularly in distinguishing between different cell populations and identifying anomalies.
Innovation Solution
A method utilizing flow cytometry to automatically group and characterize biological cells in N-dimensional space, comparing sample data with reference files to identify anomalies, optimizing data processing and reducing reliance on operator skill.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If visual analysis by an operator is used for grouping cells into clusters, then flexibility in handling complex cases is improved, but labor time and operator dependency increase significantly
Solution Approach 1:
The patent segments the analysis process into two distinct phases: an automatic preliminary grouping phase that handles routine cases using algorithmic clustering methods, and a manual review phase that only activates when anomalies are detected. This segmentation allows the system to achieve high-speed processing for normal samples while maintaining operator flexibility for complex cases, resolving the contradiction between speed and adaptability.
Solution Approach 2:
The system performs preliminary automatic grouping and anomaly detection before operator intervention is needed. By pre-processing the data through automated clustering algorithms and only presenting abnormal cases to operators, the system eliminates unnecessary manual analysis time while preserving operator expertise for cases that truly require it.
2Productivity
If conventional hematology analyzers are used for blood count analysis, then basic cell counting is achieved, but reproducibility and statistical reliability are compromised due to manual intervention
Solution Approach 1:
The system implements automated feedback loops where clustering results are continuously evaluated against statistical criteria and reference values. The algorithm automatically adjusts grouping parameters and validates results, ensuring consistent reproducible outcomes. This feedback mechanism eliminates operator variability while maintaining high productivity in cell counting and analysis.
3Measurement precision
If sample dilution is performed to enable distinct measurements of cells, then measurement accuracy is improved, but analysis time increases due to the need to process larger sample volumes
Solution Approach 1:
The patent replaces mechanical/time-consuming manual cell-by-cell examination with automated electronic detection systems including light scattering, fluorescence detection, and impedance measurement. These electronic systems can rapidly analyze diluted samples without requiring prolonged observation time, thus maintaining measurement precision while dramatically reducing analysis time.
4Measurement precision
If red blood cells are selectively lysed to concentrate leukocytes, then statistical representativeness of leukocyte populations is improved, but sample preparation complexity increases
Solution Approach 1:
The system uses automated lysis reagents as intermediaries that selectively destroy red blood cells while preserving leukocytes. This chemical intermediary approach simplifies the overall process by replacing complex mechanical separation methods with a single reagent addition step, thereby improving leukocyte concentration accuracy while actually reducing preparation 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
Enhances the reproducibility and speed of analyzing biological samples by providing relevant diagnostic recommendations with minimal operator intervention and cost, leveraging high-speed equipment.
Implementation Method 1
measurement of cell volume by impedance (Coulter effect)
Implementation Method 2
optical absorption measurements
Implementation Method 3
diffraction at different angles generated by the passage of each cell in a laser beam
Implementation Method 4
fluorescence measurement of nucleic acids made fluorescent by one or more fluorochromes
Implementation Method 5
flow cytometry consists of performing at least one hydrodynamic focusing and passing the blood cells one by one through a measuring device
Data Source
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AI summary
The invention relates to a method for analysing a biological sample containing biological cells, and an analysing device for implementing the analysing method. The analysing method comprises a step of measuring cytometry parameters for each biological cell contained in a biological sample; a step of determining, for each biological cell of the biological sample, a point in space with N dimensions, the coordinates of which are defined as a function of the cytometry parameters measured for the corresponding biological cell, wherein N is an integer greater than or equal to 3; a step of automatically grouping together the points in different clusters of cells as a function of the cytometry parameters measured, so as to define a sample cluster file; and a step of comparing the sample cluster file with reference cluster files, each of the reference cluster files being defined on the basis of cytometry parameters of a respective pathological or abnormal biological sample.