Digital Holography for Non-Destructive 3D Cell Culture State Evaluation
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Solution Overview
Problem
Current methods for evaluating the state of three-dimensional cell cultures are invasive, time-consuming, and require significant manpower, as they often involve destructive processes or two-dimensional evaluations that struggle to assess cell density and survival within spheres of varying sizes in a three-dimensional space.
Innovation Solution
A non-destructive method using digital holography to generate phase difference images of cell aggregates, deriving an index value from these images to quantify the randomness of phase differences, allowing for easy determination of cell state, survival rate, and undifferentiated rates without destroying the cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional two-dimensional culture evaluation methods are applied to three-dimensional cell cultures, then cell state can be evaluated, but the evaluation process becomes time-consuming and requires significant manpower
Solution Approach 1:
The patent replaces manual mechanical evaluation processes with automated image processing and analysis systems. Conventional methods requiring human observation and manual counting of cells are substituted with computer-based algorithms that automatically analyze cell aggregate images, extract features, and determine cell states, thereby eliminating time-consuming manual operations while maintaining evaluation accuracy
Solution Approach 2:
The patent creates digital copies of cell aggregates through high-throughput imaging to replace physical manual examination. Multiple cell aggregates are imaged and analyzed simultaneously through computational methods, allowing parallel processing of numerous samples without requiring proportional increases in manual labor time
2Measurement precision
If destructive evaluation methods are used to assess cell density and survival, then accurate cell state information can be obtained, but the cells are destroyed in the process
Solution Approach 1:
The patent replaces destructive mechanical or chemical evaluation methods with non-invasive optical imaging and computational analysis. Instead of methods that require cell lysis, staining, or physical disruption to assess cell density and survival, the system uses light-based imaging to capture cell aggregate characteristics and employs algorithms to extract quantitative information about cell state without causing any harm to the cells
Solution Approach 2:
The patent introduces light as an intermediary medium to obtain cell information without direct contact or damage. Optical imaging serves as a mediator that allows remote, non-contact measurement of cell aggregate properties, enabling accurate assessment of cell density and survival rates while keeping the biological samples intact and viable for further experiments
3Productivity
If three-dimensional cell culture is used for mass production, then cell production capacity increases, but evaluation of cell quality becomes more difficult
Solution Approach 1:
The patent divides the complex task of three-dimensional cell aggregate analysis into multiple independent processing stages: image acquisition, preprocessing, feature extraction, and classification. By segmenting the evaluation process into discrete computational steps, the system can efficiently handle large numbers of cell aggregates while maintaining accurate quality assessment at each stage
Solution Approach 2:
The patent develops a universal evaluation system that can assess multiple cell quality parameters simultaneously using the same imaging and analysis platform. The system extracts various features from cell aggregate images including size, shape, texture, and optical properties, enabling comprehensive quality evaluation across different cell types and culture conditions without requiring separate specialized methods for each parameter
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 accurate, non-destructive evaluation of cell cultures by quantifying the randomness of phase differences in cell aggregates, reducing evaluation time and manpower while providing insights into cell state and survival rates within three-dimensional cultures.
Implementation Method 1
generating a phase difference image of an aggregate of a plurality of cells from a hologram obtained by imaging the aggregate
Implementation Method 2
generating a phase difference image of an aggregate of a plurality of cells from a hologram obtained by imaging the aggregate
Data Source
Figure 1
Figure 2A~2D
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AI summary
A determination method of non-destructively and easily determining a state of an aggregate of a plurality of cells formed by three-dimensional culture is provided. A determination method according to the disclosed technology includes generating a phase difference image of an aggregate of a plurality of cells from a hologram obtained by imaging the aggregate, deriving a first index value that indicates a randomness of an array of a phase difference amount in a plurality of pixels constituting the phase difference image, and determining a state of the cells constituting the aggregate on the basis of the first index value.