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dc.contributor.authorZhao, Yongxin
dc.contributor.authorBucur, Octavian
dc.contributor.authorIrshad, Humayun
dc.contributor.authorChen, Fei
dc.contributor.authorWeins, Astrid
dc.contributor.authorStancu, Andreea L
dc.contributor.authorOh, Eun-Young
dc.contributor.authorDiStasio, Marcello
dc.contributor.authorTorous, Vanda
dc.contributor.authorGlass, Benjamin
dc.contributor.authorStillman, Isaac E
dc.contributor.authorSchnitt, Stuart J
dc.contributor.authorBeck, Andrew H
dc.contributor.authorBoyden, Edward S
dc.date.accessioned2021-10-27T19:57:33Z
dc.date.available2021-10-27T19:57:33Z
dc.date.issued2017
dc.identifier.urihttps://hdl.handle.net/1721.1/133995
dc.description.abstractExpansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a 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, 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, a process that previously required electron microscopy, and we demonstrate high-fidelity computational discrimination between early breast neoplastic lesions for which pathologists often disagree in classification. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research.
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.relation.isversionof10.1038/NBT.3892
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.sourcePMC
dc.titleNanoscale imaging of clinical specimens using pathology-optimized expansion microscopy
dc.typeArticle
dc.relation.journalNature Biotechnology
dc.eprint.versionAuthor's final manuscript
dc.type.urihttp://purl.org/eprint/type/JournalArticle
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.date.updated2019-07-19T13:27:29Z
dspace.orderedauthorsZhao, Y; Bucur, O; Irshad, H; Chen, F; Weins, A; Stancu, AL; Oh, E-Y; DiStasio, M; Torous, V; Glass, B; Stillman, IE; Schnitt, SJ; Beck, AH; Boyden, ES
dspace.date.submission2019-07-19T13:27:30Z
mit.journal.volume35
mit.journal.issue8
mit.metadata.statusAuthority Work and Publication Information Needed


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