(6p) Optical Imaging of the Brain at Nanoscopic Resolution

Conventional fluorescence microscopy suffers from tradeoffs in resolution, imaging depth and photobleaching. In this work, we implement a novel scalable 3d imaging strategy to overcome these limitations by combining the physical expansion and clearing capabilities of hydrogel-based expansion microscopy (ExM) and the fast and high resolution imaging volumetric capabilities of advanced light microscopy. We show that (a) rational design of hydrogel monomers can lead to isotropic expansion of biological samples down to 10-100 nm length scale; (b) integration of expanded tissue-hydrogel composites with ultra-fast, low-photobleaching light-sheet microscopy can realize nanoscopic imaging of brain tissues up to 1000 times faster than electron microscopy (EM) and super-resolution light microscopy. Finally, we discuss tissue expansion/clearing technology’s broad implications for neuronal network tracing and functional omics.

Teaching Interests:

Broadly in the fields of material science, chemistry, nanoscience and nanotechnology, brain science, biomaterials and bioengineering. Five years of teaching experience at Harvard University as a Teaching Fellow.