Oblique lightsheet STORM for tissue samples

Abstract

While single-molecule localization microscopy (SMLM) offers superior super-resolution for biology, typical SMLM system using highly-inclined off-axis illumination limits an imaging depth to only a few microns from a coverslip surface. Alternative SMLM system using light-sheet illumination has extended the accessible depth for whole cells or small embryos, but may be less practical as it requires specialized or dedicated sample devices. Furthermore, for typical tissue samples (laterally a few millimeters or wider), the lateral lightsheet illumination is no longer applicable. Here, we demonstrate oblique light-sheet SMLM (obSTORM) that provides a facile and practical platform with a full compatibility with tissue samples. By using a single-objective, inclined lightsheet and directly detecting single molecules along the oblique plane, obSTORM opens new doors for tissue-level super-resolution imaging.