Oblique plane single-molecule localization microscopy for thick samples

We introduce single-molecule oblique plane microscopy (obSTORM) to directly image oblique sections of thick samples into depth without lengthy axial stack acquisition. Using oblique light-sheet illumination and oblique fluorescence detection, obSTORM offers uniform super-resolution throughout imaging depth in diverse biological specimens from cells to tissues. In particular, we demonstrate an isotropic resolution of ∼51 nm over a depth of 32 μm for a tissue sample, and comparable resolution over a depth of 100 μm using fluorescent beads.