Brillouin Cytometry Imaging for Parallel Subcellular Cell Mapping

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Solution Overview

Problem

Current Brillouin microscopy setups are limited by the need for point-by-point scanning due to high background noise and low throughput, making it difficult to achieve high-resolution, high-density, and non-invasive subcellular mechanical mapping of cells, especially for understanding cell migration and metastatic potential in cancer cells.

Innovation Solution

A method and system utilizing a virtually imaged phased array (VIPA) or Fabry-Perot etalon with a CCD or CMOS camera for simultaneous measurement of multiple points in a sample, enabling high-resolution two-dimensional Brillouin imaging by reshaping the illuminating light beam and using a microfluidic device to analyze subcellular mechanical properties without contact.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If point-by-point scanning is used in conventional Brillouin spectroscopy, then measurement precision is improved, but productivity deteriorates

Engineering Contradiction:
ImproveBrillouin frequency shift measurement precisionVSAvoidThroughput efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent divides the sample into multiple measurement points arranged in a grid pattern, allowing parallel measurement of multiple locations simultaneously. This segmentation approach enables the system to maintain measurement precision at each point while dramatically increasing overall productivity by measuring many points in parallel rather than sequentially

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent transitions from one-dimensional point-by-point scanning to two-dimensional parallel imaging by using a camera detector to capture spatially-resolved Brillouin spectra across the entire sample area simultaneously. This dimensional change from sequential scanning to parallel imaging resolves the contradiction between measurement precision and productivity

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Measurement precision

If high-resolution spectrometer is used to separate Brillouin frequency shift, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
ImproveBrillouin frequency shift separation precisionVSAvoidSpectrometer complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical scanning spectrometers with a simpler optical system combining a diffraction grating and camera detector. This substitution maintains the ability to resolve Brillouin frequency shifts while dramatically reducing mechanical complexity and enabling parallel acquisition across multiple spatial points

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

3Measurement precision

If point-by-point scanning is used, then measurement precision is improved, but loss of time increases

Engineering Contradiction:
ImproveBrillouin spectrum analysis precisionVSAvoidAcquisition time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent implements continuous parallel measurement across the entire sample area using a camera detector that captures Brillouin spectra from all measurement points simultaneously. This eliminates the time loss associated with sequential scanning while maintaining spectral resolution through advanced signal processing of the parallel data

Inventive Principle:
Principle #20Continuity of useful 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 approach allows for rapid acquisition of subcellular mechanical information, enhancing throughput and reducing background noise, enabling the classification of cells based on their mechanical properties and providing insights into cell behavior and metastatic potential.

Implementation Method 1

Brillouin scattering is the phenomena of inelastic light scattering induced by acoustic phonon of a material

Methodology Applied
Scientific EffectBrillouin scattering: Brillouin Scattering

Implementation Method 2

an optical arrangement to induce a spectral dispersion

Methodology Applied
Scientific EffectSpectral dispersion: Dispersion (of waves)

Data Source

PatentEP3394939B1System and method of label-free cytometry based on brillouin light scattering
Publication Date: 2024.11.20 CANON US LIFE SCIENCES INC
  • EP3394939B1 patent drawingFigure 1~3
  • EP3394939B1 patent drawingFigure 4(a)~4(f)
  • EP3394939B1 patent drawingFigure 5~6

AI summary

The present invention relates to a method and system for a label-free cell analysis based on Brillouin light scattering techniques. Combined with microfluidic technologies according to the present invention, Brillouin spectroscopy constitutes a powerful tool to analyze physical properties of cells in a contactless non-disturbing manner. Specifically, subcellular mechanical information can be obtained by analyzing the Brillouin spectrum of a cell. Furthermore, a novel configuration of Brillouin spectroscopy is provided to enable simultaneous analysis of multiple points in a cell sample.