Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy
Boyden, Edward S.Note: Order does not necessarily reflect citation order of authors.
MetadataShow full item record
CitationZhao, Y., O. Bucur, H. Irshad, F. Chen, A. Weins, A. L. Stancu, E. Oh, et al. 2017. “Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy.” Nature biotechnology 35 (8): 757-764. doi:10.1038/nbt.3892. http://dx.doi.org/10.1038/nbt.3892.
AbstractExpansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding the specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin (H&E), and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ~70 nm resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes, and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, which previously required electron microscopy (EM), and demonstrate high-fidelity computational discrimination between early breast neoplastic lesions that to date have challenged human judgment. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34868849
- HMS Scholarly Articles