Lensless Cell State Discrimination via Digital Reconstruction
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Solution Overview
Problem
Current methods for monitoring cell development in incubators or biological reactors are cumbersome, expensive, and can affect cell development due to the need for microscopes and fluorescent labeling, and are limited by lensless imaging techniques when particle concentration increases.
Innovation Solution
A method using a light source and a matrix photodetector to acquire images of cells, applying a digital reconstruction algorithm to determine characteristic quantities of the light wave at various distances, allowing classification of cells as alive or dead based on profile changes along the propagation axis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If lensless imaging is used to simplify the observation system, then device complexity is reduced, but measurement precision deteriorates when particle concentration increases
Solution Approach 1:
The patent transitions from 2D image plane analysis to 3D spatial analysis by performing digital reconstruction at multiple distances along the propagation axis. This dimensional extension allows the system to maintain measurement precision in lensless imaging by capturing depth information through characteristic quantity profiles at different reconstruction distances, thereby resolving the precision limitation when particle concentration increases.
2Measurement precision
If fluorescent labeling is used to monitor cell state, then measurement precision is improved, but object-affected harmful factors increase due to impact on cell development
Solution Approach 1:
The patent enables cells to serve as their own labels by utilizing their intrinsic optical properties (refractive index, absorption characteristics) to generate diffraction patterns and characteristic quantity profiles. This self-service approach eliminates the need for external fluorescent tags, thereby maintaining measurement precision while avoiding harmful effects on cell development.
Solution Approach 2:
The patent replaces the chemical/biological labeling mechanism (fluorescent tags) with a physical optical measurement mechanism (diffraction-based lensless imaging). This substitution eliminates the need for chemical modifiers that could affect cell viability, while maintaining detection accuracy through physical optical property analysis.
3Measurement precision
If microscope-based observation is used to achieve accurate cell analysis, then measurement precision is improved, but device complexity and cost increase
Solution Approach 1:
The patent extracts and removes the complex optical components (lenses, objectives, eyepieces) from the traditional microscope system, retaining only the essential function of image formation through direct propagation. By taking out the unnecessary complex elements and using simple lensless geometry with digital reconstruction, the system achieves comparable measurement precision with dramatically reduced device complexity.
Solution Approach 2:
The patent creates a digital copy of the optical field information through computational reconstruction algorithms. Instead of relying on complex optical magnification and image formation, the system captures the optical field directly and reconstructs the cell images computationally, achieving accurate cell analysis with a simplified optical setup that eliminates traditional microscope complexity.
4Area of stationary object
If traditional lensless imaging is used to extend field of observation, then area of observation is improved, but measurement precision deteriorates due to insufficient characterization at high particle concentration
Solution Approach 1:
The patent extends the observation capability from 2D spatial distribution to 3D spatial-frequency space by performing digital reconstruction at multiple distances along the propagation axis. This dimensional extension provides depth discrimination and enables accurate particle characterization even at high concentrations, maintaining measurement precision across the extended field of observation.
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
Enables simple, inexpensive, and reliable discrimination between living and dead cells without labeling, providing an extended field of observation and accurate cell state determination.
Implementation Method 1
illumination of said sample using a light source, the light source producing an incident light wave propagating towards the sample along a propagation axis
Implementation Method 2
the matrix photodetector is exposed to a light wave comprising interference between the incident light wave and a diffraction wave produced by each cell
Implementation Method 3
the matrix photodetector is exposed to a light wave comprising interference between the incident light wave and a diffraction wave produced by each cell
Data Source
Figure 1
Figure 2~3C
Figure 4A~4B
AI summary
The invention is a method for identifying the state of a cell (1, 2, 3, 4, 5) contained in a sample (14) including illuminating the sample using a light source (11), the latter producing an incident light wave (12) propagating toward the sample (14), then acquiring, using a matrix-array photodetector (16), an image of the sample (14), the sample (14) being placed between said light source (11) and the matrix-array photodetector (16) in such a way that the matrix-array photodetector (16) is exposed to a light wave (22) that is the result of interference between the incident light wave (12) and a diffraction wave produced by each cell (1, 2, 3, 4, 5). The method is characterised in that it includes applying a numerical reconstruction algorithm to the image acquired by the matrix-array photodetector (16), in order to estimate a characteristic quantity of the light wave reaching the matrix-array detector (16), at a plurality of distances (z) from the matrix-array photodetector (16). The value of the characteristic quantity, or its variation as a function of distance (z), allowing the state of the cell (1, 2, 3, 4, 5) to be determined from among predetermined states.