Development of a handheld rapid air sensing system to monitor and quantify SARS-CoV-2 in aerosols in real-time

开发手持式快速空气传感系统，实时监测和量化气溶胶中的 SARS-CoV-2

• 批准号: 10273983
• 负责人: Ricardo Mancebo
• 金额: $ 272.32万
• 依托单位: GENENDEAVOR, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10273983
• 关键词: 2019-nCoV; Address; Aerosols; Air; Applications Grants; Aspirate substance; Benchmarking; Biophotonics; COVID-19; COVID-19 detection; COVID-19 monitoring; COVID-19 pandemic; COVID-19 patient; Cell Culture Techniques; Cell Nucleus; Cessation of life; Chemicals; Collection; Communities; Contact Tracing; Country; DNA; Data; Detection; Development; Devices; Dose; Drops; Environment; Enzyme Inhibitor Drugs; Enzymes; Goals; Guidelines; Handwashing; Health; Hospitals; Hour; Human; Individual; Interdisciplinary Study; Investigation; Knowledge; Laboratories; Lead; Ligation; Lung; Masks; Measurement; Measures; Methods; Monitor; Nasal cavity; Onset of illness; Performance; Photons; Polymerase Chain Reaction; Predisposition; Preparation; Process; Protocols documentation; Quarantine; RNA; RNA-Directed DNA Polymerase; Reaction Time; Reading; Reagent; Reporting; Research; Research Proposals; Reverse Transcription; Risk; Risk Management; Role; SARS-CoV-2 infection; SARS-CoV-2 transmission; Safety; Sampling; Schools; Severity of illness; Signal Transduction; Social Distance; Speed; Standardization; Symptoms; System; Technology; Testing; Time; Uncertainty; Viral; Viral Load result; Virus; Virus Inactivation; Workplace; aerosolized; air monitoring; air sampling; base; chemical kinetics; design; detection platform; disease transmission; epidemiology study; foot; genomic RNA; high risk; human coronavirus; infection rate; infection risk; innovation; insight; knowledge base; laboratory equipment; monitoring device; novel; particle; photon-counting detector; portability; prevent; real time monitoring; sensor; solid state electronics; tissue culture; tool; transmission process; viral detection

Project Summary The ability to rapidly monitor SARS-CoV-2 in aerosol—drop particles <5 μm in size that evaporate into droplet nuclei and become suspended in air—at the point of presentation is critical to managing the risk of infection by airborne transmission as people return to their communities, workplaces, and schools during the COVID-19 pandemic. However, current enzyme-based methods lack sensitivity, speed, simplicity, and require lab equipment—hence, lack the capability for real-time point-of-presentation (POP) monitoring. In the absence of a real-time POP monitoring capability, SARS-CoV-2 transmission remains poorly understood. In this application, a multidisciplinary research approach that integrates innovations in rapid-kinetic chemical auto-ligation, non- enzymatic isothermal signal amplification, solid-state electronics, and biophotonics is proposed to enable the development of a novel air monitoring system (AMS) that detects and quantifies aerosolized SARS-CoV-2 at the point of presentation in real-time. Recent advances in viral culturing protocols, air sampling technology, and single-photon detection capability will provide the framework for a collaborative research endeavor to establish a new paradigm to address the knowledge gap between the spread of COVID-19 and SARS-CoV-2 aerosol transmission. Therefore, the proposal is aimed at transforming the way COVID-19 is currently researched by providing a tool to enable unparalleled studies that will significantly advance the current knowledgebase. These transformative studies could ultimately guide a new field of investigations that lead to a better understanding of COVID-19 spread, such as viral exposure vs. risk, viral decay rate vs. infectivity, and viral load vs. infectious dose in SARS-CoV-2 airborne transmission. At a minimum, the proposed three research objectives will provide a basic understanding of COVID-19 aerosol transmission. Firstly, current air sampling systems use a multi-step workflow that takes several hours to complete and requires lab equipment, reagents, and significant hands-on time. The goal of objective 1 is to combine air sampling and detection into a one-step real-time POP AMS device that yields SARS-CoV-2 quantification results in less than 5 minutes, without lab equipment or reagents. Secondly, viral inoculum, or initial dose of virus, aspirated into the nasal cavity and lungs has been associated with disease onset and severity. The goal of objective 2 is to optimize and validate AMS to correlate readings from the air monitoring device with tissue-culture infectious dose (TCID50) and reverse transcription polymerase chain reaction (RT-PCR) quantities. These parameters can then later be applied to Human studies to determine the Human infectious dose of SARS-CoV-2 by aerosol transmission. Thirdly, field-based testing in hospitals will provide a means to beta test AMS performance in high-risk environments. The goal of objective 3 is to calibrate AMS measurements with RT-PCR cycle-threshold (Ct) values and cell-culture TCID50 viability results and then benchmark with results from high-risk environments taken from around the world to correlate SARS-CoV-2 aerosol concentrations with global infection rate, as a potential for establishing threshold levels.

项目摘要 在气溶胶中快速监测SARS-COV-2的能力 - 蒸发成液滴的颗粒<5μm 核并被悬浮在空气中 - 在演示点，对于管理感染风险至关重要 随着人们在Covid-19期间返回社区，工作场所和学校的空气传播， 大流行。但是，当前基于酶的方法缺乏灵敏度，速度，简单性，并且需要实验室 设备 - 因此，缺乏实时露天点（POP）监视的能力。在没有 实时POP监视能力，SARS-COV-2传输仍然知之甚少。在此应用程序中 一种多学科研究方法，将创新整合到快速运动化学自动结合中，非 - 提出了酶等热信号扩增，固态电子设备和生物光谱剂以实现 开发一种新型的空气监测系统（AMS），该系统检测和量化了雾化的SARS-COV-2 AT 实时演示点。病毒文化方案，空气抽样技术和 单光子检测能力将为协作研究努力提供框架 一个新的范式来解决Covid-19和Sars-Cov-2气溶胶之间的知识差距 传播。因此，该提案旨在改变Covid-19当前研究的方式 提供一种工具来实现无与伦比的研究，从而大大推动当前知识库。 变革性研究最终可以指导一个新的调查领域，从而更好地理解 COVID-19传播，例如病毒暴露与风险，病毒衰减率与感染与病毒负荷与感染 SARS-COV-2空降传输中的剂量。拟议的三个研究目标至少将提供 对COVID-19的基本理解。首先，当前的空气采样系统使用多步 工作流程需要几个小时才能完成，需要实验室设备，试剂和重要的动手 时间。目标1的目的是将空气采样和检测结合到一步实时POP AMS中 产生SARS-COV-2定量的设备在不到5分钟的情况下，没有实验室设备或试剂。 其次，被吸入鼻腔和肺的病毒接种物或病毒初始剂量已与 疾病发作和严重程度。目标2的目的是优化和验证AMS以关联读数 从带有组织文化感染剂量（TCID50）和逆转录的空气监测装置。 聚合酶链反应（RT-PCR）量。然后可以将这些参数应用于人类研究 通过气溶胶传播确定SARS-COV-2的人类感染剂量。第三，基于现场测试 医院将为高风险环境中的Beta测试AMS表现提供一种手段。目标3的目标 是用RT-PCR周期阈值（CT）值和细胞培养物TCID50的活力来校准AMS测量值 结果，然后与来自世界各地的高风险环境的结果进行基准测试 SARS-COV-2气溶胶浓度具有全球感染率，是建立阈值水平的潜力。