Quantitative Phase Microscopy for Noninvasive Glycogen Detection
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Solution Overview
Problem
Current methods for determining cell type based on glycogen content, such as PAS staining and Raman spectroscopic imaging, are invasive, prone to cell damage, and face challenges in distinguishing glycogen-specific signals from other medium components, limiting noninvasive and accurate assessment of pluripotent stem cell differentiation states.
Innovation Solution
A cell determination method utilizing optical path length data measured by quantitative phase microscopy to differentiate between high and low glycogen content cells, allowing noninvasive and easy identification of pluripotent stem cell types, including undifferentiated and differentiated states, by correlating glycogen content with optical path length and using this indicator to distinguish between cell types in a medium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PAS staining method is used to detect glycogen, then glycogen content can be detected, but cells cannot be observed noninvasively and require staining treatment
Solution Approach 1:
The patent replaces the chemical staining mechanism of PAS staining with an optical measurement mechanism using quantitative phase microscopy. The QPM system measures optical path length differences caused by glycogen accumulation without requiring chemical stains, thereby achieving noninvasive detection while maintaining measurement capability.
Solution Approach 2:
The patent introduces optical path length as an intermediary parameter to indirectly measure glycogen content. Instead of directly detecting glycogen through chemical staining, the system measures the optical path length difference caused by glycogen accumulation in cells, which serves as a noninvasive proxy for glycogen quantification.
2Ease of operation
If Raman spectroscopic imaging is used to observe cells without staining, then noninvasive observation is achieved, but the intensity of illuminated light is strong causing cell damage
Solution Approach 1:
The patent replaces the Raman spectroscopy mechanism with quantitative phase microscopy. QPM uses phase information of transmitted light rather than Raman scattering, allowing observation with much lower light intensity that does not damage cells, while still achieving noninvasive imaging capability.
Solution Approach 2:
The patent changes the detection parameter from Raman scattering intensity to optical path length phase difference. This parameter change enables observation using lower light intensity since phase microscopy detects phase shifts rather than requiring strong illumination for scattering signal detection.
3Ease of operation
If Raman spectroscopic imaging is used to observe cells in medium, then cells can be observed without staining, but it is difficult to analyze Raman scattering light specific to cells from medium components
Solution Approach 1:
The patent uses optical path length as an intermediary that is specifically sensitive to glycogen accumulation in cells. Since glycogen has distinct optical properties that affect phase shift, the optical path length measurement selectively detects glycogen-related changes in cells while being less affected by surrounding medium components.
Solution Approach 2:
The patent focuses on measuring local optical path length changes within the cell cytoplasm where glycogen accumulates. By analyzing phase differences specifically in cellular regions rather than the entire field of view including medium, the system achieves specificity for glycogen detection even when cells are in medium.
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 noninvasive and accurate determination of cell types based on glycogen content, effectively distinguishing between undifferentiated and differentiated pluripotent stem cells, reducing the risk of cell damage and improving the quality control of stem cell cultures.
Implementation Method 1
an acquisition step of acquiring optical path length data by measuring an optical path length of the cell
Implementation Method 2
the greater the glycogen content in the cell, the longer the optical path length
Data Source
AI summary
The present invention relates to a cell determination method for determining a cell type based on a content of glycogen in a cell, including: an acquisition step of acquiring optical path length data by measuring an optical path length of the cell; a calculation step of calculating an optical path length indicator correlated with the optical path length of the cell from the obtained optical path length data; a comparison step of comparing the calculated optical path length indicator with a threshold; and a determination step of determining whether the cell is a cell type having a high glycogen content in the cell or a cell type having a low glycogen content in the cell, based on the comparison result.