Bioengineering Seminar: Exploring light and life: Nanophotonics and AI for molecular sequencing and single-cell phenotyping

Noon – 1 p.m.
Stanley Hall, Room 177

Jennifer ​(Jen) Dionne, PhD, Stanford University

Abstract:
The earth’s biosphere is incredibly information-rich, with estimated information transmission rates exceeding those of the technosphere by 9 orders of magnitude. Here, we present nanophotonic methods that may enable unprecedented data about biochemical systems, at rates previously unattainable. First, we describe our lab’s Si-photonic “Very-large-scale Integrated high-Q Nanophotonic Pixels” (VINPix). These photonic resonators achieve high-Q factors, subwavelength mode volumes, and controlled dipole-like radiation, with Q-factors from the thousands to millions, and resonator densities exceeding 10M/cm2. By combining VINPix arrays with acoustic bioprinting for local chemical functionalization, we develop Si-chip microsystems and the associated AI framework to detect multi-omic signatures on the same platform. As a first application, we describe integration of these sensors with autonomous underwater robots from Monterey Bay Aquarium Research Institute for targeted gene, protein, and metabolite detection. Then, we describe how these chips can be used for peptide and glycoconjugate sequencing. We tether peptides from major histocompatibility complex to each resonator, and use dynamic Raman spectroscopy to monitor the cleavage of each amino acid from the distal terminus. We also show how these resonators, combined with computational metadynamics, can be used to identify previously unseen molecular species. Finally, we show how these resonators enable subcellular differentiation and functional state characterization of cells in the tumor immune microenvironment (TIME), including the ability to predict drug resistance, macrophage polarization, and T-cell activation state. Collectively, we anticipate that these nanophotonic platforms can provide completely new data on the biosphere – from improved understanding of molecular communication systems, to optimization of novel biochemical sensing platforms for health and sustainability.