Fast 3D imaging of whole organs at cellular resolution by high-throughput muti-scale light sheet microscopy

Rapid 3D imaging of whole organs at cellular resolution is vital to pathological research, but this task remains challenging in light sheet microscopy due to the compromise between axial resolution and field of view. In the meanwhile, needed magnification varies when doing different analysis. Here, we report on a high-throughput multi-scale light sheet microscopy which combines adjustable beam shaping system providing continuous imaging magnification from 1.26X~12.6X, sample holding device for fast sample switching, modulation mask to generate thin optical sectioning and large illumination field, capable of imaging a lung lobe with cellular resolution (~2.8μm), centimeter-scale field of view (1.1cm×0.8cm) within 1 minute. We demonstrate the imaging of hundreds of lung lobes of mice and other large-scale tissue. Using our ultra-high throughput light sheet microscopy with multiple magnification, we are able to quickly get the 3D view of the whole tissue and the statistical data of the volume of tumors, the number tumor cells and so on for further biological analysis.