Flow Cytometer Angular Light Detection for Particle Characterization
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Solution Overview
Problem
Current flow cytometry techniques fail to effectively utilize the wealth of data obtained from particles, often losing valuable information by reducing complex waveform data to pulse height, area, and width, which can lead to misidentification of cell types and properties, especially when cells have similar morphology or refractive indices.
Innovation Solution
A method and system that detect radiated light from particles in multiple angular directions using multiple detectors, transforming the waveforms using basis functions to obtain coefficients that characterize particle properties, enabling detailed analysis of physical and biological properties without relying on fluorescence markers or cell fixation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If waveform data is reduced to pulse height, area, and width for analysis, then the complexity of data processing is reduced, but valuable information about particle properties is lost
Solution Approach 1:
The patent applies dimensionality change by transforming waveform data from the time domain to the frequency domain using Fourier transformation. This converts the complex time-dependent waveform into frequency spectrum components, allowing comprehensive particle characterization without reducing to simple pulse parameters. The frequency domain representation preserves all original information while enabling sophisticated multi-parametric analysis.
Solution Approach 2:
The patent changes the parameter representation by using multiple frequency components (spectral parameters) instead of traditional pulse height, area, and width. By analyzing the frequency spectrum of the waveform, the system extracts multiple independent parameters that collectively provide more comprehensive particle information while maintaining manageable data complexity through structured spectral analysis.
2Measurement precision
If multiple detectors are used to detect radiated light in multiple angular directions, then the measurement precision of particle properties is improved, but the device complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the detection task across multiple detectors positioned at different angular positions. Each detector captures radiated light from a specific angle, and the system processes each detector's waveform independently through Fourier transformation. This segmented approach enables comprehensive angular resolution for precise particle characterization while maintaining modular, manageable system complexity.
Solution Approach 2:
The patent implements multi-functionality by using the same signal processing methodology (Fourier transformation and spectral analysis) for all detectors regardless of their angular positions. This universal processing approach allows the system to handle multiple detectors efficiently, extracting particle properties from each angular perspective using identical algorithms, thereby managing complexity through standardized processing pipelines.
3Measurement precision
If Fourier transformation is applied to waveform data, then the analysis of particle properties such as size, shape, and refractive index is enhanced, but the computational requirements increase
Solution Approach 1:
The patent applies preliminary action by performing Fourier transformation on the waveform data immediately upon acquisition from each detector, before further analysis. This pre-processing step converts time-domain signals to frequency-domain spectra early in the measurement pipeline, enabling subsequent particle property analysis to proceed with already-transformed data, thereby optimizing the overall computational workflow and energy efficiency.
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 allows for accurate, label-free characterization and sorting of particles by providing a comprehensive analysis of particle properties, including refractive index and morphology, with improved discrimination between similar cell types and states, enhancing the precision and efficiency of flow cytometric analysis.
Implementation Method 1
The optical signals, derived from radiated light, for example from emission of fluorescence or from light scatter
Implementation Method 2
The optical signals, derived from radiated light, for example from emission of fluorescence or from light scatter
Data Source
AI summary
The invention relates to a method and system for characterizing particles using a flow cytometer comprising detecting radiated light from the particles using two or more detectors positioned to allow for the detection in two or more angular directions and generating a waveform, as a digital representation for the detected radiated light for each of said angulation direction. The waveforms are transformed using one or more basis functions to obtain one or more coefficients characterizing the waveform. The one or more coefficients characterizing the waveform preferably correspond to properties of the particle(s), thereby enabling analysis of physical properties of the particles (such as size, shape, refractive index) or biological properties of the particles (such as cell type, cell cycle state or localization or distribution of molecules within the cell and/or on the cell surface). In preferred embodiments the method and system are used for a label-free sorting of particles, in particular biological cells.