Abstract
Expansion microscopy enables conventional diffraction limit microscopy to achieve super-resolution imaging. However, the enlarged tissue lacks an objective lens with sufficient working distance that can image tissues with whole-brain-scale coverage. Here, we present expansion tomography (ExT) to solve this problem. We have established a modified super-absorbent hydrogel (ExT gel) that possesses high mechanical strength and enables serial sectioning. ExT gel enables tissue and cell imaging and is compatible with various fluorescent labeling strategies. Combining with the high-throughput light-sheet tomography (HLTP) system, we have shown the capability of large volume imaging with nanoscale resolution of mouse brain intact neuronal circuits. The ExT method would allow image samples to support super-resolution imaging of intact tissues with virtually unlimited axial extensions.