Multi-immersion oblique plane microscope (miOPM): a reconfigurable platform for high-resolution light-sheet fluorescence microscopy.

Light-sheet fluorescence microscopy (LSFM) enables gentle, rapid and efficient volumetric imaging of biological specimens. Despite its potential, LSFM has fragmented into multiple variants, each narrowly optimized for specific samples or imaging regimes, limiting its broad applicability. Here we introduce the multi-immersion oblique plane microscope (miOPM), an adaptable LSFM platform for high-resolution imaging ranging from subcellular dynamics to whole organisms and cleared tissues. miOPM supports seamless interchangeability of oil, water and air objectives and maintains diffraction-limited performance across a refractive index range of 1.33 to 1.51. It is compatible with standard sample mounting, current clearing protocols and high-throughput 3D imaging. We leverage miOPM to image diverse biological specimens at multiple spatial scales. By expanding the adaptability and ease of use of LSFM, miOPM is poised to democratize advanced 3D imaging.