Adaptive optics correction of specimen-induced aberrations in single-molecule switching microscopy

Single-molecule switching (SMS) microscopy is a super-resolution method capable of producing images with resolutions far exceeding that of the classical diffraction limit. However, like all optical microscopes, SMS microscopes are sensitive to, and often limited by, specimen-induced aberrations. Adaptive optics (AO) has proven beneficial in a range of microscopes to overcome the limitations caused by aberrations. We report here on new AO methods for SMS microscopy that enable the feedback correction of specimen-induced aberrations. The benefits are demonstrated through two-dimensional and three-dimensional STORM imaging. We expect that this advance will broaden the scope of SMS microscopy by enabling deep-cell and tissue-level imaging.