Blind Sparse Inpainting Reveals Cytoskeletal Filaments with Sub-Nyquist Localization

Single molecule location microscopy (SMLM) such as STORM and (F)PALM has enabled super-resolution microscopy beyond the diffraction limit. However, the temporal resolution of SMLM is limited by the time needed to acquire sufficient sparse single-molecule activation events to successfully construct a super-resolution image. Here a novel fast SMLM technique is developed to achieve super-resolution imaging within a much shortened duration. This technique does not require faster switching rate or higher activation density which may cause signal degradation or photo damage/bleaching, but relies on computational algorithms to reconstruct a high-density super-resolution image from a low-density one using the concept of blind image inpainting. Our results demonstrate that the technique reduces the acquisition time by up to two orders of magnitude compared to the conventional method while achieving the same high resolution. We anticipate our technique to enable future real-time live cell imaging with even higher resolution.