Light-Sheet Fluorescence Microscopy for Multiscale Biological Imaging

Fluorescence microscopy, through fluorescent fusion proteins and indirect immunofluorescence, has transformed imaging in biology. However, the diffraction limit of light prevents interrogation of cellular structures beyond the diffraction limit. In this chapter, we explore a particular super-resolution imaging technology, Expansion Microscopy (ExM), and how it can be used to optically clear biological specimens, as well as increase the resolution of conventional microscopes through physical magnification. Lastly, we cover how ExM can be combined with light-sheet fluorescence microscopy to provide high speed and high spatial resolution volumetric imaging of biological samples.