Single-shot computational phase nanoscopy visualizing organelles

Fluorescence microscopy is a powerful bioimaging technique for specific labeling and observing targeted structures. However, there are limitations when observing living cells, including phototoxicity, which damages cells; photobleaching, which restricts observation time; and the necessity to stain specific structures, which limits its application scope. On the other hand, phase contrast imaging has a long history of label-free, live-cell imaging, including techniques like Zernike phase contrast (ZPC) and differential interference contrast (DIC) microscopy. However, ZPC has the limitation of constraining the illumination aperture, thereby limiting spatial resolution, and the orientation dependency of DIC can result in information loss. Furthermore, the phase shifts obtained by ZPC and DIC are not quantitative. Here, we implement single-shot computational phase nanoscopy on a commercial microscope using a camera with filter arrays. We report on a variety of organelles observed with this microscope.