Spatial Domain Phase Matrix for Biological Cell Analysis
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Solution Overview
Problem
Current methods for analyzing biological tissue cells are destructive, time-consuming, and prone to background noise, especially when using Fourier transforms to solve the transport of intensity equation, which can lead to inaccurate phase information.
Innovation Solution
A method involving the acquisition of two images with different focal heights, computation of a contrast matrix, and subsequent phase matrix to assess cell characteristics, working in the spatial domain rather than the frequency domain, which simplifies the phase information deduction and reduces noise.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Fourier transform is used to solve the transport of intensity equation, then phase information can be obtained, but background noise in the digital image leads to inaccurate phase information
Solution Approach 1:
The patent extracts only the essential information needed for phase calculation by using a simplified spatial domain approach. Instead of processing the entire frequency spectrum with Fourier transform, the method extracts phase information directly from intensity variations in the spatial domain, effectively removing the noise component that affects frequency domain transformations.
Solution Approach 2:
The patent creates a simplified mathematical model that copies only the necessary relationships between intensity and phase. By using a direct spatial domain relationship rather than a full Fourier transform, the method replicates the essential phase information without copying the noise artifacts that occur in frequency domain processing.
2Difficulty of detecting and measuring
If manual counting of cells is performed, then cell visibility is improved through staining, but the process becomes tedious, time consuming and costly
Solution Approach 1:
The patent replaces the mechanical process of manual cell counting with an automated optical measurement system. Instead of manually examining and counting stained cells, the system uses light transmission measurements and computational algorithms to automatically determine cell characteristics, eliminating the time-consuming manual process while maintaining measurement accuracy.
Solution Approach 2:
The patent changes the measurement parameter from visual inspection of stained cells to quantitative light transmission measurements. By measuring the phase shift or intensity variation of light passing through cells, the system obtains quantitative data about cell properties without requiring staining or manual counting, thus reducing time consumption while improving measurement objectivity.
3Difficulty of detecting and measuring
If staining is applied to make cells visible, then cells can be counted and studied, but the staining influences the cells and alters the study results
Solution Approach 1:
The patent uses the cells' natural optical properties to generate the measurement signal. Instead of requiring external staining agents to make cells visible, the method exploits the inherent refractive index differences between cells and the surrounding medium, allowing cells to 'serve themselves' as the measurement target without external modification that could alter their behavior or structure.
Solution Approach 2:
The patent replaces the chemical staining process with a physical optical measurement process. Instead of using chemical agents that may interact with and alter cell properties, the system uses light transmission measurements that physically interact with cells without chemical modification, thereby maintaining cell integrity and study result reliability.
4Measurement precision
If more than two images are acquired for phase information, then measurement accuracy may improve, but the process becomes more complex and time consuming
Solution Approach 1:
The patent applies partial action by using only the minimum necessary number of images (two images) to obtain accurate phase information. Instead of acquiring multiple images at different focal planes or using complex multi-step procedures, the method achieves sufficient measurement precision with just two images, avoiding the excessive complexity that would arise from more extensive image acquisition sequences.
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 non-destructive, accurate, and efficient analysis of biological tissue cells by deriving phase information without the need for complex noise filtering, enhancing flexibility and reducing time consumption.
Implementation Method 1
When radiation, such as a beam of light, passes through a cell in a culture medium having a different refractive index to the cell, there is a phase change which depends on the relative refractive index of the cell and the thickness of the cell.
Implementation Method 2
When radiation, such as a beam of light, passes through a cell in a culture medium having a different refractive index to the cell
Data Source
AI summary
At least first and second digital images of the sample are acquired having different focal heights relative to a platform on which the cells are disposed. A contrast matrix is produced having elements computed in dependence upon the difference between the values of the corresponding pixels in the first and second images. A phase matrix is produced by convolution of the contrast matrix with a predetermined distance matrix. The phase matrix is used to assess characteristics of the sample, such as the presence of cells in the sample or the heights of cells in the sample.