1State Key Laboratory for Mesoscopic Physics, Department of Physics, Peking University, Beijing 100871, China
2State Key Laboratory of Membrane Biology, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China
3School of Physics, Xi’an Jiaotong University, Xi’an 710049, China
4Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, China
5Peking University Yangtze Delta Institute of Optoelectronics, Nantong 226010, China
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 type light-sheet microscope with a mini-prism used as an 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 300 nm could be achieved without deconvolution. The proposed method also enables easy transform of a conventional fluorescence microscope to high performance light-sheet microscopy.