CAREER: Resonant Dielectric Optical Metasurfaces for Single-Cell Extracellular Vesicles (EV) Analysis

Vanderbilt University, Nashville TN

Investigators

Abstract

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Once thought of as a means for cells to expel wastes, in recent years, extracellular vesicles (EVs) released by virtually all cells in humans have been shown to contain biological information molecules such as proteins and deoxyribonucleic acid (DNA), through which cells can communicate with neighboring or distant cells. This EV-mediated cell-to-cell communication has been implicated in the spread and progression of diseases such as cancer to other parts of the body. Current gold standard methods for EV isolation and analysis involve measurement of EVs contributed from multiple cells and cannot distinguish the differences in the quantity and phenotypes of EV secretion between cells. Addressing this gap in knowledge is key to enhancing our understanding of EVs and better enabling their applications in therapeutics and diagnostics. This CAREER proposal investigates novel optical nanostructures inspired by early theoretical works in quantum mechanics, which when illuminated with light will generate forces to selectively capture EVs as they are released by a single cell without damage, and analyze the single-cell secreted EVs to enable correlating the function of the EVs directly to their cells of origin. The PI along with graduate and undergraduate students will carry out strong outreach and education activities including the construction and placement of an optical tweezer system interfaced with an iPad at the Adventure Science Center museum in Nashville, Tennessee to educate k-12 students and visitors on how light can be used to hold and move small objects on a cellular scale. The PI and graduate students will also develop international education activities that will expose undergraduate students and researchers in West Africa to the computer-aided design of optical nanostructures. The research project will investigate the physics of photonic Bound States in the Continuum for the generation of electromagnetic fields and optical force at the nanoscale. Bound States in the Continuum (BIC) was initially introduced as a mathematical curiosity in quantum mechanics and has recently emerged as a new way to engineer radiative losses for robust control of light at the nanoscale for a variety of applications in lasers, sensors, and chip-scale optical communications. This project brings BIC-inspired metasurfaces to the domain of single-cell omics towards the in-situ proteomics analysis of single-cell secreted EVs without any cross-contamination from other cells. The intellectual significance of the planned activities includes: (a) an understanding of the role of the geometry of the BIC metasurface elements in minimizing the in-plane and out-of-plane radiative losses to achieve superior electromagnetic field enhancements that is robust to fabrication imperfections; (b) demonstration of nanoscale optical trapping of nanosized EVs using BICs in dielectric metasurfaces for the first time; (c) an understanding of quasi-BIC induced optical force for trapping, three-dimensional transport, release and controlled uptake of EVs by a recipient cell, a capability not possible with any approach reported to date; (d) the in-situ proteomic analysis to profile single-cell secreted EV molecular cargos; and (e) an understanding of whether argonaute proteins are selected cargos in single-cell secreted EVs. The unique capabilities provided by the proposed BIC dielectric metasurface system will allow the PI and the team to associate the properties of EVs directly to their cell sources up to the resolution of single cells, a capability that has so far remained elusive. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.