Reflective Ultrathin Light-Sheet Microscopy with Isotropic 3D Resolutions

Light-sheet fluorescence microscopy (LSFM) has played an important role in bio-imaging due to its advantages of high photon efficiency, fast speed and long-term imaging capabilities. The perpendicular layout between LSFM excitation and detection often limits the 3D resolutions as well as their isotropy. Here, we report on a reflective light-sheet microscope with a mini-prism used as optical path reflector. The conventional high NA objectives can be used both in excitation and detection with this design. Isotropic resolutions in 3D down to 300nm could be achieved without deconvolution. The proposed method also enables easy transform of conventional flrorescence microscope to high performance light-sheet microscopy.