Single-frame wide-field nanoscopy based on ghost imaging via sparsity constraints

Single-molecule, localization-based, wide-field nanoscopy often suffers from low time resolution because the localization of a single molecule with high precision requires a low emitter density of fluorophores. In addition, to reconstruct a super-resolution image, hundreds or thousands of image frames are required, even when advanced algorithms, such as compressive sensing and deep learning, are applied. These factors limit the application of these nanoscopy techniques for living cell imaging. In this study, we developed a single-frame, wide-field nanoscopy system based on ghost imaging via sparsity constraints (GISC), in which a spatial random phase modulator is applied in a wide-field microscope to achieve random measurement of fluorescence signals. This method can effectively use the sparsity of fluorescence emitters to enhance the imaging resolution to 80 nm by reconstructing one raw image using compressive sensing. We achieved an ultrahigh emitter density of 143 mu m(-2) while maintaining the precision of single-molecule localization below 25 nm. We show that by employing a high-density of photo-switchable fluorophores, GISC nanoscopy can reduce the number of sampling frames by one order of magnitude compared to previous super-resolution imaging methods based on single-molecule localization. GISC nanoscopy may therefore improve the time resolution of super-resolution imaging for the study of living cells and microscopic dynamic processes. (c) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement