Fluorescence microscopy helps observe specific labeled molecules but has some limitations. First, the need for labeling can affect the physiological function of targets and is incompatible with clinical applications. Phototoxicity is not negligible in high-speed, high-resolution imaging. Illumination with longer wavelengths can mitigate phototoxicity, but it results in lower spatial resolution. Photobleaching also restricts the observation duration and quantification of signals. Phase contrast imaging has a long history of label-free, live cell imaging, including Zernike phase contrast (ZPC) and differential interference contrast (DIC) microscopy. ZPC usually has a limited spatial resolution, and fine structures in the cells are often hidden by the halo artifact. Orientation dependency of DIC causes information loss. Moreover, phase shifts obtained by ZPC and DIC are not quantitative. Here, we report our computational approach to quantitative phase microscopy. Our method allows us to observe fine structures and rapid dynamics for a long time with minimal modifications to the optics of commercial microscopes.
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