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The urgency to probe and understand dynamics in biology is impeded by a major challenge in bioinstrumentation development. The large dynamic range of biological processes—interactions of molecules within milliseconds result in changes across whole-organisms over years—calls for instruments with both high spatiotemporal resolution and large-scale long-term coverage. However, high resolution measurement often requires frequent and invasive sampling, which limits the spatiotemporal coverage of the instruments. In this seminar, I will present two independent yet complementary approaches that tackle this challenge. First, I will introduce a new paradigm—syringe-injectable mesh electronics—for seamlessly merging electronics with mammalian brains. The gliosis-free and three-dimensional interpenetrated brain-electronics interface enables stable stimulation and recording from the same neurons and neural circuits over a year. I will then discuss the application of mesh electronics to retina electrophysiology in awake mice. Second, I will describe a novel multimodal optical scope with adaptive imaging correction (MOSAIC) to observe subcellular dynamics inside multicellular organisms with high spatiotemporal resolution, large imaging depth and low phototoxicity. I will present applications of MOSAIC to various model organisms, including transcription factor kinetics in embryoid bodies, axonal targeting in Drosophila, cancer metastasis and embryogenesis in Caenorhabditis elegans and zebrafish. Both the electrical and optical approaches opened up new windows to probe dynamics in biology with minimum perturbation and expanded spatiotemporal ranges.

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