Plaque Detection Using Phase Field Imaging and Transport of Intensity Equation
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Solution Overview
Problem
Current cell culture imaging systems are laborious and require stringent aseptic conditions, lacking efficiency in distinguishing between live and lysed cells, and are not effective in detecting viral plaques, which complicates cell culture maintenance and analysis.
Innovation Solution
The system employs Phase Field in focus and non-focused images to detect cell objects and differentiate between live and lysed cells using phase behavior, and utilizes the Transport of Intensity Equation to recover phase information from bright field images, enabling plaque detection through adaptive thresholding and segmentation processes, and integrates machine learning for model building and augmentation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If bright field optics are used to image cells, then the imaging system is simple and easy to operate, but the contrast between cells and surrounding media is very low making it difficult to detect cell objects and distinguish between live and lysed cells
Solution Approach 1:
The patent segments the imaging process into multiple components: acquiring multiple images at different focus planes (above and below the focal plane), processing each image separately through thresholding and watershed algorithms, and combining results to produce final cell segmentation. This segmentation allows the simple bright field optics to achieve accurate cell detection by breaking down the complex detection task into manageable steps.
Solution Approach 2:
The patent introduces a new dimension by capturing images at multiple focus planes (z-axis) rather than relying on a single focused image. By acquiring images both above and below the focal plane and using the Transport of Intensity Equation to recover phase information from these out-of-focus images, the system transforms 2D bright field images into 3D phase information, enabling accurate distinction between live and lysed cells without complex optics.
2Productivity
If traditional imaging methods are used to detect viral plaques, then the process is straightforward, but the system cannot effectively distinguish plaque regions from normal cells due to lack of sensitivity to lysed cell materials
Solution Approach 1:
The patent extracts the phase information from the bright field images using the Transport of Intensity Equation, separating the useful phase data about cell structure from the harmful intensity variations caused by lighting and focus errors. This extraction enables the system to detect the subtle optical differences between intact cells and lysed cell regions, allowing accurate plaque detection without manual intervention.
Solution Approach 2:
The patent implements feedback through automated image processing that continuously refines cell segmentation and plaque detection. The watershed algorithm uses feedback from the distance transform and thresholding results to iteratively improve the segmentation, and the system provides feedback to users through quantitative measurements of cell confluence, morphology, and plaque detection results, enabling continuous optimization of detection accuracy.
3Reliability
If manual cell culture maintenance is performed, then aseptic conditions can be maintained, but the process is laborious and requires highly trained personnel reducing productivity
Solution Approach 1:
The patent enables cell culture self-monitoring and self-diagnosis through automated imaging and analysis. The system automatically detects cell confluence, morphology changes, and plaque formation, providing real-time feedback that reduces the need for manual intervention. This self-service capability maintains reliability through consistent monitoring while dramatically improving productivity by eliminating labor-intensive manual checks.
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 provides objective data and improved monitoring of cell cultures, enabling consistent treatment and tracking of cell growth, accurate confluence measurements, and enhanced imaging capabilities for cell status quantification and biological outcome analysis.
Implementation Method 1
Phase contrast optics utilizes the different phase delay of the inner material and the surrounding media. For live cells, the cell fluid is encased in a membrane that is under tension which results in the membrane and material organizing itself into compact shapes. When cells lyse, the membrane is compromised and the tension is lost resulting in the material losing its compact shape.
Implementation Method 2
This behavior is the phenomena behind the Transport of Intensity Equation methodology for recovering the phase of the bright field illuminated subjects.
Implementation Method 3
Normal image capture for bright field microscopic work attempts to seek the plane of best focus for the subjects. In some embodiments, images focused on planes that differ from the plane of best focus are used to define the phase behavior of the subject.
Data Source
AI summary
Method and apparatus for performing a plaque detection by using above focus and below focus images. Plaque is also detected by a method and apparatus using test and training data captured on an imaging system, building a new model for a specific virus/cell/protocol type to detect plaques, using the models in runtime systems to detect plaques and augmenting the models based on automatically calculated false positive and false negative counts and percentages taken from test runs and/or runtime data.