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

该奖项由2021年美国救援计划法案提供全部或部分资金（Public Law 117-2）.曾经被认为是细胞排出废物的一种手段，近年来，人类几乎所有细胞释放的细胞外囊泡（EV）已被证明含有生物信息分子，如蛋白质和脱氧核糖核酸（DNA），通过这些通道，细胞可以与邻近的或远距离的细胞通信。这种EV介导的细胞间通讯与癌症等疾病向身体其他部位的传播和进展有关。目前用于EV分离和分析的金标准方法涉及测量来自多个细胞的EV，并且不能区分细胞之间EV分泌的量和表型的差异。解决这一知识差距是提高我们对电动汽车的理解并更好地使其在治疗和诊断中应用的关键。这项CAREER提案研究了受量子力学早期理论工作启发的新型光学纳米结构，当用光照射时，它将产生选择性捕获EV的力，因为它们被单细胞释放而不受损伤，并分析单细胞分泌的EV，以使EV的功能直接与其起源细胞相关联。PI沿着研究生和本科生将开展强有力的推广和教育活动，包括在田纳西州纳什维尔的冒险科学中心博物馆建造和放置一个与iPad连接的光学镊子系统，以教育K-12学生和游客如何利用光在细胞尺度上固定和移动小物体。研究生和研究生还将开展国际教育活动，使西非的本科生和研究人员接触到光学纳米结构的计算机辅助设计。该研究项目将研究连续统中光子束缚态的物理学，以产生纳米级的电磁场和光学力。连续体中的束缚态（BIC）最初是作为量子力学中的数学好奇心而引入的，最近已经成为一种新的方法来设计辐射损耗，用于在纳米尺度上对激光器，传感器和芯片级光通信中的各种应用进行鲁棒控制。该项目将BIC启发的元表面引入单细胞组学领域，对单细胞分泌型EV进行原位蛋白质组学分析，而不会受到其他细胞的任何交叉污染。计划活动的智力意义包括：（a）理解BIC超颖表面元件的几何形状在最小化面内和面外辐射损耗以实现对制造缺陷鲁棒的上级电磁场增强中的作用;（B）首次在电介质超颖表面中使用BIC演示纳米尺寸EV的纳米级光学捕获;（c）了解准BIC诱导的光学力，用于受体细胞捕获、三维运输、释放和控制EV摄取，这是迄今报道的任何方法都不可能实现的能力;和（e）了解argonaute蛋白是否是单细胞分泌型EV中的选择性货物。BIC介电超颖表面系统提供的独特功能将使PI和团队能够将电动汽车的特性直接与其电池源相关联，最高可达单个电池的分辨率，这一能力迄今为止仍然难以捉摸。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.