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

职业：用于单细胞胞外囊泡 (EV) 分析的共振介电光学超表面

• 批准号: 2143836
• 负责人: Justus Ndukaife
• 金额: $ 50.8万
• 依托单位: Vanderbilt University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2143836&HistoricalAwards=false
• 关键词: CAREER; Resonant; Dielectric; Optical; Metasurfaces

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.

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.这种EV介导的细胞对细胞通信与癌症等疾病的扩散和进展有关。电动汽车分离和分析的当前黄金标准方法涉及对多个细胞造成的电动汽车的测量，并且无法区分细胞之间EV分泌的数量和表型的差异。在知识中解决这一差距是增强我们对电动汽车的理解并更好地实现其在治疗和诊断方面的应用的关键。该职业建议调查了受量子力学早期理论作品启发的新型光学纳米结构，当用光照射时，该纳米结构将产生力量，以选择性地捕获电动汽车，因为它们被单个电池释放而没有损坏，并分析单细胞分泌的EVS以启用将电动汽车的功能直接与原始源相关联。 PI与研究生和本科生一起将在田纳西州纳什维尔的Adventure Science Center Museum与iPad连接的光学镊子系统进行强大的宣传和教育活动，包括田纳西州纳什维尔的iPad与iPad接触，以教育K-12学生和访客如何使用光线来握住和移动小物体。 PI和研究生还将开发国际教育活动，将西非的本科生和研究人员暴露于光学纳米结构的计算机辅助设计中。该研究项目将研究纳米凯斯莱舞会的电磁场和电磁场和光学力量的连续体的光子结合状态的物理。最初将连续体（BIC）中的结合状态作为量子力学中的数学好奇心引入，最近已成为一种新的方法，用于设计辐射损失，以在纳米级在纳米级的光线控制光线，传感器和Chip-Scale Scale-Scale Optical Communications中的各种应用。该项目将受BIC启发的元面条带到单细胞OMIC的领域，用于对单细胞分泌EV的原位蛋白质组学分析，而无需其他细胞的交叉污染。计划活动的智力意义包括：（a）理解BIC跨表面元素在最小化平面内和平面外辐射损失方面的作用，以实现对制造不完美不完美的优质电磁场增强的优势电磁场增强； （b）首次使用介电上部中的BICS纳米级纳米级EV的纳米级光捕获； （c）对准BIC诱导的光学作用的理解，用于捕获，三维运输，释放和受控电动室的摄取电动电动机的摄取，迄今为止报告的任何方法都无法使用能力； （d）原位蛋白质组学分析，以介绍单细胞分泌的EV分子cargos； （e）了解在单细胞分泌的电动汽车中是否选择了Argonaute蛋白。 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.

项目成果

Merging toroidal dipole bound states in the continuum without up-down symmetry in Lieb lattice metasurfaces

• DOI: 10.1515/nanoph-2023-0686
• 发表时间: 2023-07
• 期刊: Nanophotonics
• 影响因子: 7.5
• 作者: Guodong Zhu;Sen Yang;Justus C. Ndukaife

Hybrid Optical and Diffusiophoretic Nanomanipulation Using All-Dielectric Anapole-Enhanced Thermonanophotonics

• DOI: 10.1021/acsphotonics.3c00983
• 发表时间: 2023-09
• 期刊: ACS Photonics
• 影响因子: 7
• 作者: I. Hong;Theodore Anyika;Chuchuan Hong;Sen Yang;Justus C. Ndukaife

Single-peak and narrow-band mid-infrared thermal emitters driven by mirror-coupled plasmonic quasi-BIC metasurfaces

• DOI: 10.1364/optica.514203
• 发表时间: 2023-10
• 期刊: Optica
• 影响因子: 10.4
• 作者: Sen Yang;Mingze He;Chuchuan Hong;Josh Nordlander;Jon-Paul Maria;J. Caldwell;Justus C. Ndukaife