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香槟分校CCSS-1509391 1-提案标题：用纳米光学机械流体实现无标记单病毒识别2-项目目标简介：我们的目标是实验演示对单病毒纳米颗粒的同时光学和机械检测，从而实现快速无标记识别。3摘要：3A非技术摘要纵观历史，病毒疾病对人类造成了巨大的损害。对病毒病原体的快速识别可以使医疗保健做出快速反应，以遏制重大疫情，甚至快速开发药物。过去十年爆发的H1N1、H5N1、SARS和埃博拉病毒突显了这一紧迫需求。同时检测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。与提供有限信息的现有光学或机械方法相比，这是一个新的视角。该方案通过一种新型的纳米流体光学机械谐振器解决了测量吞吐量、灵敏度和粒子识别等相关的基本问题。有朝一日，这种设备可能会被部署在现场，用于无标签识别病毒病原体，并产生医疗当局的快速反应。在药理学研究中，这些设备可以帮助药物发现。拟议的工作基本上是跨学科的，从教育角度来看具有很高的价值。该项目利用先进的实验工具，为光学物理、固体力学和流体力学的各个层次(研究生、本科生、高中生)的培训提供了丰富的机会。这项工作的STEM教育影响将通过发展和分布关于光学测量微粒布朗运动的教育活动来扩大。这些活动将面向当地学校的K-12学生，并通过现有的校园合作伙伴进行更广泛的分发。还将为研究和教育工作招聘一名本科生研究助理，优先考虑代表性不足的群体。3b技术摘要目前，用于检测病毒纳米颗粒的快速无标记技术依赖于光子传感或振动质量传感，但不能两者兼而有之，并且只能提供有限的一维信息。例如，机械方法主要根据谐振器的质量负载和相关频率的原理进行操作。通过这种方式，粒子的质量可以以极高的分辨率估计，但如果没有额外的假设，就无法获得大小和密度。相比之下，光子学方法依赖于光学共振频率的移动或光学模式分裂。这提供了有关纳米颗粒的极化率、大致大小的信息，但不允许进一步鉴定。因此，在没有使用特定抗体结合或化学过程的情况下，病原体的无标记鉴定(相对于单纯的检测)仍然存在模糊性。同时具有光学和机械性质可以揭示单个病毒粒子的大小、质量密度和光学密度(或偏振性)，并有助于缩小蛋白质折叠和病毒结构属性。该项目有多个目标(1)阐明使用纳米光机械流体设备同时进行光学机械测量来检测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)发展一种提高机械共振传感吞吐量的方法，利用同时的光学信息来在时空上定位纳米颗粒。(4)通过使用纳米光机械流体谐振器，不仅基于单个病毒颗粒的光学性质，而且基于其质量，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.