Towards label-free single virus identification with nano-optomechanofluidics

利用纳米光机械流体学实现无标记单一病毒识别

• 批准号: 1509391
• 负责人: Gaurav Bahl
• 金额: $ 36.18万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1509391&HistoricalAwards=false
• 关键词: Towards; label; free; single; virus

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.

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： 走向无标记的单病毒识别与nano-optomechanofluidics 2-项目目标的简要说明：我们的目标是实验证明同时光学和机械传感的单病毒纳米粒子，可以允许快速无标记识别。3-摘要：3A非技术摘要纵观历史，病毒性疾病对人类造成了巨大的损害。快速识别病毒病原体可以实现快速医疗响应，以阻止重大疫情，甚至快速药物开发。在过去十年中，H1N1、H5 N1、SARS和埃博拉病毒的爆发凸显了这一迫切需求。同时感测病毒的光学和机械特性可以允许快速识别单个病毒颗粒而无需任何化学测试。与现有的仅提供有限信息的仅光学或仅机械方法相比，这是一个新的视角。该建议解决了相关的基本问题的测量吞吐量，灵敏度和颗粒识别的装置的一种新型的纳米流体光机械谐振器。这样的设备有一天可以部署在现场，用于病毒病原体的无标签识别，并由医疗机构迅速做出反应。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，从教育的角度来看具有很高的价值。该项目为各级学生（研究生、本科生、高中生）在光学物理、固体力学和流体力学交叉领域的培训提供了丰富的机会，使用先进的实验工具。这项工作的STEM教育影响将通过开发和分发关于微粒布朗运动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发。一个本科生研究助理也将被招募的研究和教育工作，优先向代表性不足的群体。3B技术摘要目前，快速无标记技术检测病毒纳米粒子依赖于光子传感或振动质量传感，但不能两者兼而有之，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加载原理和相关频率进行操作。通过这种方式，粒子的质量可以用极高的分辨率来估计，但如果没有额外的假设，则无法获得尺寸和密度。相比之下，光子方法依赖于光学谐振频率的偏移或光学模式分裂。这提供了关于纳米颗粒的极化率、近似尺寸的信息，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，病原体的无标记鉴定（与仅仅检测相反）仍然存在模糊性。同时具有光学和机械特性可以揭示单个病毒粒子的大小，质量密度和光密度（或极化率），并可以帮助缩小蛋白质折叠和病毒结构特性。(2)建立光学和机械噪声源的模型，并考虑辐射压力和光学机械反作用的影响。(3)发展一种机械共振感测的处理量提升方法，借由同时使用光学资讯来时空定位奈米粒子。(4)通过使用纳米光机电流体谐振器，提高检测和识别单个病毒颗粒的能力，不仅基于其光学特性，还基于其质量。