Towards label-free single virus identification with nano-optomechanofluidics

PI: Gaurav Bahl，机械科学与工程伊利诺伊大学厄巴纳-香槟分校CCSS-1509391 1-提案标题：用纳米光力学流体技术实现无标签单病毒鉴定2-项目目标简述：我们的目标是通过实验证明单病毒纳米颗粒的同时光学和机械传感，可以实现快速无标签鉴定。摘要：历史上，病毒性疾病对人类造成了巨大的危害。对病毒病原体的快速识别可以使医疗保健快速反应，以遏制重大疫情，甚至可以快速开发药物。在过去十年中，H1N1、H5N1、SARS和埃博拉病毒的爆发突出了这一迫切需要。同时感知病毒的光学和机械特性，可以在不进行任何化学测试的情况下快速识别单个病毒颗粒。与现有的仅提供有限信息的光学或机械方法相比，这是一个新的视角。本提案通过一种新型纳米流体光机械谐振器解决了测量吞吐量，灵敏度和颗粒识别的相关基本问题。这样的设备可能有一天会被部署在现场，用于病毒病原体的无标签识别，并由卫生保健当局产生快速反应。在药理学研究中，这些装置可以帮助药物发现。建议的工作基本上是跨学科的，从教育的角度来看具有很高的价值。本项目为各级学生（研究生、本科生、高中生）提供了丰富的机会，利用先进的实验工具，在光学物理、固体力学和流体力学的交叉领域进行训练。这项工作的STEM教育影响将通过发展和分发关于微观粒子布朗运动的光学测量的教育活动来扩大。这些活动将针对当地学校的K-12学生，并通过现有的校园合作伙伴进行更广泛的分销。还将征聘一名本科生研究助理，负责研究和教育工作，优先考虑代表性不足的群体。目前，检测病毒纳米颗粒的快速无标签技术要么依赖光子传感，要么依赖振动质量传感，但不能两者兼得，而且只能提供有限的一维信息。例如，机械方法主要是根据谐振器的质量负载和相关频率的原理进行操作的。用这种方法，可以以极高的分辨率估计粒子的质量，但如果没有额外的假设，就无法获得粒子的大小和密度。相反，光子方法依赖于光共振频率的移位或光模分裂。这提供了关于极化率的信息，纳米颗粒的大致尺寸，但不允许进一步鉴定。因此，在不使用特异性抗体结合或化学过程的情况下，对病原体的无标签识别（与仅仅检测相反）仍然存在歧义。同时具备光学和机械特性可以揭示单个病毒粒子的大小、质量密度和光学密度（或极化率），并有助于缩小蛋白质折叠和病毒结构特性的范围。本项目有多个目标：(1)阐明利用纳米光力学流体装置同时进行光力学测量来感知单个病毒粒子的基本限制。(2)建立光学和机械噪声源的模型，并考虑辐射压力和光机械反作用的影响。(3)利用同步光学信息对纳米粒子进行时空定位，开发一种提高机械共振传感吞吐量的方法。(4)利用纳米光机电流谐振器，不仅根据单个病毒颗粒的光学性质，而且根据它们的质量，提高检测和识别单个病毒颗粒的能力。

PI: Gaurav Bahl, Mechanical Science and EngineeringUniversity of Illinois at Urbana-Champaign CCSS-1509391 1- Proposal Title: Towards label-free single virus identification with nano-optomechanofluidics2- Brief description of project goals:We aim to experimentally demonstrate simultaneous optical and mechanical sensing of single virus nanoparticles that can permit rapid label-free identification.3- Abstract:3a Nontechnical abstractThroughout history, viral diseases have inflicted great damage to human populations. Swift identification of a viral pathogen can enable a rapid healthcare response for arresting major outbreaks, and even for speedy drug development. This pressing need is highlighted by outbreaks of H1N1, H5N1, SARS, and Ebolavirus over the last decade. Simultaneous sensing of optical and mechanical properties of viruses could permit the rapid identification of individual virus particles without any chemical tests. This is a new perspective in comparison to existing optical-only or mechanical-only methods that provide limited information. This proposal addresses the associated fundamental problems of measurement throughput, sensitivity, and particle identification by means of a novel nanofluidic opto-mechanical resonator. Such devices could some day be deployed in the field for the label-free identification of viral pathogens, and for generating a swift response by healthcare authorities. In pharmacological studies, these devices could assist in drug discovery.The proposed work is fundamentally interdisciplinary and of high value from an educational perspective. This project provides rich opportunities for the training of students at alllevels (graduate, undergraduate, high school) at the intersection of optical physics, solid mechanics, and fluid mechanics, using advanced experimental tools. The STEM education impact of this work will be broadened through the development and distribution of educational activities on the optical measurement of Brownian motion of microparticles. These activities will betargeted towards K-12 students at local schools, with wider distribution through existing on-campus partners. An undergraduate research assistant will also be recruited for the research and educational efforts with preference towards underrepresented groups.3b Technical abstractCurrently, fast label-free techniques for detecting viral nanoparticles rely on either photonic sensing or on vibrational mass sensing, but not both, and can only provide limited one-dimensional information. For instance, mechanical methods primarily operate on the principle of mass-loading of a resonator and the associated frequency. In this manner, the mass of a particle can be estimated with extremely high resolution, but size and density are not obtainable without additional assumptions. Photonic methods, in contrast, rely on the shift of optical resonance frequency or optical mode splitting. This provides information on the polarizability, approximate size of a nanoparticle, but does not permit further identification. As a result, there remains an ambiguity in the label-free identification of a pathogen (as opposed to mere detection) without the use of specific antibody binding or chemical processes. Having both optical and mechanical properties can shed much needed light on a single virion's size, mass density, and optical density (or polarizability), and could help narrow down the protein folding and virus structural properties.This project has multiple objectives (1) Elucidate the fundamental limits of sensing single virions with simultaneous optomechanical measurements using a nano-optomechanofluidic device. (2) Develop models of optical as well as mechanical noise sources, and incorporate the effects of radiation pressure and optomechanical back-action.(3) Develop a method of throughput enhancement in mechanical resonance sensing, by using simultaneous optical information to spatiotemporally locate the nanoparticles.(4) Improve the ability to detect and identify single virus particles, not only based on their optical properties but also their mass, through the use of nano-optomechanofluidic resonators.