In Situ Super-Resolution Imaging of Organoids and Extracellular Matrix Interactions via Phototransfer by Allyl Sulfide Exchange-Expansion Microscopy (PhASE-ExM).

3D organoid models have recently seen a boom in popularity, as they can better recapitulate the complexity of multicellular organs compared to other in vitro culture systems. However, organoids are difficult to image because of the limited penetration depth of high-resolution microscopes and depth-dependent light attenuation, which can limit the understanding of signal transduction pathways and characterization of intimate cell-extracellular matrix (ECM) interactions. To overcome these challenges, phototransfer by allyl sulfide exchange-expansion microscopy (PhASE-ExM) is developed, enabling optical clearance and super-resolution imaging of organoids and their ECM in 3D.