Grid-Free Localization Algorithm Using Low-Rank Hankel Matrix for Super-Resolution Microscopy

Localization microscopy, such as STORM/PALM, can reconstruct super-resolution images with a nanometer resolution through the iterative localization of fluorescence molecules. Recent studies in this area have focused mainly on the localization of densely activated molecules to improve temporal resolutions. However, higher density imaging requires an advanced algorithm that can resolve closely spaced molecules. Accordingly, sparsity-driven methods have been studied extensively. One of the major limitations of existing sparsity-driven approaches is the need for a fine sampling grid or for Taylor series approximation which may result in some degree of localization bias toward the grid. In addition, prior knowledge of the point-spread function (PSF) is required. To address these drawbacks, here we propose a true grid-free localization algorithm with adaptive PSF estimation. Specifically, based on the observation that sparsity in the spatial domain implies a low rank in the Fourier domain, the proposed method converts source localization problems into Fourier-domain signal processing problems so that a truly grid-free localization is possible. We verify the performance of the newly proposed method with several numerical simulations and a live-cell imaging experiment.