Glaser, A. K. et al. Nat. Commun. 10, 2781 (2019).

Tissue-clearing methods enable imaging within large, otherwise intact samples, such as whole tissues and even animals. Light-sheet microscopy has become a method of choice for imaging cleared samples, due to its high speed and relatively low light doses. However, existing light-sheet microscopes can place severe constraints on sample size and mounting geometry, and can be challenging to adapt to different sample-clearing methods due to differences in the samples’ refractive indices. Glaser et al. have developed an open-top light-sheet microscope that bypasses these challenges to facilitate high-throughput imaging of any type of cleared tissue. The open top geometry enables large samples to simply be placed above the objectives, and the multi-immersion capability of the detection objective covers the refractive index range of published clearing methods. As a demonstration, the researchers imaged a range of cleared and expanded samples.