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Abstract_Octavian Bucur
Optical microscopes are conventional tools required in most biomedical research fields and are indispensable in clinical disciplines, such as diagnostic pathology. These conventional microscopes, however, can’t reach a resolution less than 250 nm, making the use of more expensive microscopes, such as electron/super-resolution microscopes, required in certain diagnostic pathology areas, such as those related to diagnosis and/or confirmation of kidney nephrotic syndromes. In a Harvard-MIT collaborative team effort, we developed and patented a pathology-optimized physical tissue expansion technology called Expansion Pathology (ExPath) and a rapid ExPath variant (rExPath), which enable a symmetrical physical tissue expansion (fixed tissues) of about 100 times in volume (~ 4-5 times in one dimention), in this way being able to extend the resolution limit of an optical microscope to about 70-80 nm (from ~250 nm).
Through increasing the resolution of optical microscopy, ExPath and rExPath enable a high-resolution investigation of fixed cellular and tissue samples required in many research biomedical areas. Specifically, we demonstrated a high precision classification of the early breast neoplastic lesions that are hard to classify and, for the first time, the investigation of the tertiary foot processes of the podocyte and diagnoses of specific kidney nephrotic lesions with an optical microscope, previously diagnosed and/or confirmed only with an electron microscope.
We hope that Expansion Pathology will enable routine advanced investigation of clinical specimens and improved diagnosis of a wide range of pathologies, such as cancer.
References
- Bucur O, Fu F, Calderon M, Mylvaganam GH, Ly NL, Day J, Watkin S, Walker BD, Boyden ES, Zhao Y. Nanoscale imaging of clinical specimens using conventional and rapid-expansion pathology. Nature Protocols, 2020 May;15(5):1649-1672. doi: 10.1038/s41596-020-0300-1
- Bucur O, Zhao Y. Nanoscale Imaging of Kidney Glomeruli Using Expansion Pathology. Frontiers in Medicine (Lausanne). 2018 Nov 21;5:322. doi: 10.3389/fmed.2018.00322.
- Zhao Y, Bucur O, Irshad H, Chen F, Weins A, Stancu AL, Oh EY, DiStasio M, Torous V, Glass B, Stillman IE, Schnitt SJ, Beck AH, Boyden ES. Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy. Nature Biotechnology 2017 Aug;35(8):757-764. doi: 10.1038/nbt.3892.