Direct physiological observation of subcellular dynamics is now feasible using the Lattice Light-Sheet Microscopy. It is a transformative imaging technology that spans the relevant scales in space and time because of the wide resolution range and large volumetric acquisition capability. This new imaging method allows us to record dynamics at a scale of nanometers and milliseconds, determine their consequences at a scale of microns and hours, and visualize their long-term outcome at a scale of up to several millimeters over several days.
I’ll present our past work on combined lattice light sheet microscopy with adaptive optics to achieve (Science, 2018), across large multicellular volumes, noninvasive aberration-free imaging of subcellular dynamics in vivo. Next, I’ll discuss the combination of lattice light-sheet with the physical expansion of samples (Expansion Microscopy) that enables scalable super-resolution volumetric imaging of large tissues (Science, 2019) including the complete fly brain, columns of mouse brain – datasets spanning several hundred terabytes. Finally, I will introduce our next-generation microscope design– dubbed the “Swiss army knife microscope”, which combines at least ten different modes of imaging with integrated light paths. In essence, this new microscope is designed to seamlessly switch between modes of imaging in order to alleviate the tradeoffs related to resolution, speed, invasiveness and imaging depth, which precludes any single optical microscopy to function optimally for a diverse set of biological specimens.