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Traditional optical microscopy struggles with nanoscale structures due to the diffraction limit. A research team led by Dr. Bi-Chang Chen at the Research Center for Applied Sciences, Academia Sinica, demonstrated an innovative approach for nanoscale super-resolution imaging of large biological samples using potassium (poly)acrylate-based expansion microscopy (KA-ExM) and a Bessel lightsheet microscope (ΔBLX). The research team developed a novel chemical method that physically magnifies biological specimens, such as fruit fly brains, up to 40-fold using superabsorbent potassium (poly)acrylate hydrogels with excellent mechanical strength. This allows a ~500 µm fruit fly brain to expand to ~5 mm or more, even maintaining structural integrity through iterative expansion. This technique boosts resolution to an effective 10 nm, enabling clear visualization of subcellular structures like synaptic scaffold proteins in the fruit fly brain, while retaining the advantages of multi-color fluorescence labeling. This technological leap significantly enhances research efficiency, providing robust support for exploring complex biological structures and understanding disease mechanisms in neuroscience, cell biology, and drug discovery. The research has been published on Dec 30, 2024 in Nature Communications. The research was supported by Academia Sinica, and the National Science and Technology Council.