Potassium (Poly)acrylate-Enhanced Expansion Microscopy (KA-ExM): Bridging Optical and Electron Microscopy for High-Resolution Biological Imaging｜Institute of Cellular and Organismic Biology, Academia Sinica

This study introduces a novel approach to high-resolution biological imaging by combining potassium polyacrylate-based hydrogels with Bessel lightsheet microscopy. The expansion microscopy (ExM) method achieves a 40-fold linear expansion, corresponding to a volumetric enlargement of 64,000 times. Using an axicon-based Bessel lightsheet microscope, this technique enables three-dimensional imaging at nanoscale resolution, rivaling that of electron microscopy. As demonstrated with expanded Drosophila brains, the method allows visualization of synaptic scaffold protein structures (~10 nm) across whole-brain volumes, while preserving the advantages of multicolor fluorescent labeling inherent to optical microscopy. The simplicity and speed of "Potassium Polyacrylate Expansion Lightsheet Microscopy" facilitate systematic, multicolor analyses of fixed thick biological samples, offering a powerful tool for exploring biological structures and advancing disease research with unprecedented efficiency.