A hybrid open-top light-sheet microscope for multi-scale imaging of cleared tissues

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a user-friendly system that can address diverse imaging applications with varied requirements in terms of resolution (mesoscopic to sub-micron), sample geometry (size, shape, and number), and compatibility with tissue-clearing protocols of different refractive indices. We present a hybrid system that combines a novel non-orthogonal dual-objective and conventional open-top light-sheet architecture for highly versatile multi-scale volumetric imaging. One sentence summary Glaser et al. describe a hybrid open-top light-sheet microscope to image cleared tissues at mesoscopic to sub-micron resolution and depths of up to 1 cm.