Super-solution fluorescence microscopy, such as single-molecule localization microscopy (SMLM), is effective in observing subcellular structures and achieving excellent enhancement in spatial resolution in contrast to traditional fluorescence microscopy. Recently, deep learning has demonstrated excellent performance in SMLM in solving the trade-offs between spatiotemporal resolution, phototoxicity, and signal intensity. However, most of these researches rely on sufficient and high-quality datasets. Here, we propose a physical priors-based convolutional super-resolution network (PCSR), which incorporates a physical-based loss term and an initial optimization process based on the Wiener filter to create excellent super-resolution images directly using low-resolution images. The experimental results demonstrate that PCSR enables the achievement of a fast reconstruction time of 100 ms and a high spatial resolution of 10 nm by training on a limited dataset, allowing subcellular research with high spatiotemporal resolution, low cell phototoxic illumination, and high accessibility. In addition, the generalizability of PCSR to different live cell structures makes it a practical instrument for diverse cell research.
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