Complex biological systems like the brain present a challenge: their molecular building blocks are organized with nanoscale precision, but support physiological processes and computations that occur over macroscopic length scales. Similarly, complex diseases like cancer exhibit pathological changes that are observable from the tissue level down to the molecular level. In the first part of the talk, I will introduce the Boyden lab’s technology suite for imaging large 3-D specimens with nanoscale precision. We embed a specimen in a swellable polymer, which upon exposure to water expands isotropically in size, enabling conventional diffraction-limited microscopes to do large-volume nanoscopy. We called this process expansion microscopy (ExM). We are developing strategies for multiplexed readout of anchored DNA barcodes, in order to identify and localize thousands of different kinds of biomolecule, with nanoscale precision, in cells throughout intact tissues -- a key step towards understanding the configuration of complex biological systems in normal and disease states. In the second part of the talk, I will focus on a newly developed ExM-based technology, expansion pathology (ExPath). ExPath allows examination of a broad range of clinical samples with unprecedented detail, using only conventional optical microscopes. ExPath opens up new opportunities for morphological and molecular cancer diagnosis. In addition, ExPath can serve as a powerful research tool to investigate the pathology of complex diseases such as cancers in nanoscale level.

Tools for mapping and understanding complex biological systems in normal and disease states

251st National Meeting (2016)

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