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Updated: Feb 7, 2026

Nano-fEM: Protein Localization Using Photo-activated Localization Microscopy and Electron Microscopy
Published on: December 3, 2012
Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections
Michael J Mlodzianoski1,2, Paul J Cheng-Hathaway3,4, Shane M Bemiller5
1Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
Abstract:
Application of single-molecule switching nanoscopy (SMSN) beyond the coverslip surface poses substantial challenges due to sample-induced aberrations that distort and blur single-molecule emission patterns. We combined active shaping of point spread functions and efficient adaptive optics to enable robust 3D-SMSN imaging within tissues. This development allowed us to image through 30-μm-thick brain sections to visualize and reconstruct the morphology and the nanoscale details of amyloid-β filaments in a mouse model of Alzheimer's disease.
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