Rapid detection of infectious viral particles by cluster induced exhaustive reaction

总结 2019冠状病毒病大流行对中国的卫生、经济、环境和移民构成了巨大挑战， 美方诊断能力的提高和限制政策得到了广泛实施， 遏制病毒的传播然而，美国仍有超过20万人死亡，50万人住院治疗 一个人该病毒，严重急性呼吸道综合征冠状病毒2（SARS-CoV-2），具有高度传染性， 早期感染，特别是年轻人，在他们积极传播病毒时往往没有症状 通过说话和呼吸在社区中传播。这两种传输方法通常会产生大量 与咳嗽和打喷嚏相比，气溶胶中的病毒颗粒数量较少，因此难以检测。尽管 虽然有许多类型的诊断工具可用，但目前的现场诊断技术还不足以 检测感染者散发的气溶胶中少量病毒颗粒的灵敏度和速度。黄金 标准方法聚合酶链反应（PCR）及其变体仅在实验室环境中对 检测低拷贝数病毒。散发的气溶胶是临床诊断的有吸引力的目标，因为采样 没有侵入性，检测结果直接决定一个人是否在传播病毒。到 针对上述挑战，我们将开发基于聚类诱导穷举的快速诊断技术， 反应（CIER）与几个病毒的敏感性和一次性设备的成本便士，使这种 纸装置可以在任何地方频繁使用，以在他/她即将感染之前识别感染性个体。 进一步向社区传播SARS-CoV-2。CIER理论上能够无限放大信号， 保持高特异性，因此高度适用于检测SARS-CoV-2颗粒， 抗原簇可以触发CIER传感器。提出了两个具体目标：（1）构建CIER传感器， 组装抗体、间隔区和HRP部分，优化CIER检测SARS-CoV-2的设计 超高灵敏度的病毒颗粒，以及（2）快速定量呼吸和呼吸中的SARS-CoV-2病毒颗粒 表面进行POC诊断，并通过多重检测区分流感病毒和SARS-CoV-2。这 变革性的诊断技术将具有检测SARS-CoV-2的高灵敏度和特异性 同时成本低，任何人都可以简单地使用。CIER纸的使用不仅 立即识别病毒传播者，还可节省巨大的资源浪费， 少数传染性个体。

Summary The COVID-19 pandemic has posed enormous challenges to health, economy, environment and immigration in the US. Enhancement of diagnosis capacity together with restriction policies has been widely implemented to contain the virus spreading. However, there are still over 200,000 deaths and half million hospitalized in the US alone. The virus, Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), is highly contagious while early infection particularly in young adults often exhibits no symptoms when they are actively transmitting viruses in the community through speaking and breathing. These two transmission approaches normally emit much lower number of virus particles in aerosols than coughing and sneezing, and thus are difficult to detect. Despite many types of diagnostic tools available, current on-site diagnostic technologies do not have the sufficient sensitivity and speed to detect low number of virus particles in aerosols emitted by infected people. The gold standard method, polymerase chain reaction (PCR), and its variants are only ultrasensitive in the lab setting to detect low copy number of viruses. Emitted aerosols are attractive target for clinical diagnosis because sampling is not invasive, and the detection results directly determine whether a person is spreading viruses or not. To address the above challenge, we will develop a rapid diagnostic technology based on cluster induced exhaustive reaction (CIER) with the few virus sensitivity and disposable device with the cost of pennies, so that this kind of paper device can be used frequently anywhere to identify an infectious individual immediately before he/she further spreads SARS-CoV-2 to the community. CIER enables theoretically unlimited amplification of signal while maintaining high specificity, and thus is highly applicable to detect SARS-CoV-2 particles where only the compact cluster of antigens can trigger the CIER sensor. Two specific aims are proposed: (1) Construct CIER sensor by assembling antibodies, spacer and HRP moieties, and optimize CIER’s design for detecting of SARS-CoV-2 virus particles with ultra-high sensitivity, and (2) Rapidly quantify SARS-CoV-2 virus particles in breath and on surface for POC diagnosis, and distinguish influenza virus from SARS-CoV-2 by multiplexed detection. This transformative diagnostic technology will possess ultrahigh sensitivity and specificity to detect SARS-CoV-2 viruses in exhaled air while in low cost and simple to use by any person. The use of CIER paper will not only immediately identify virus spreading people, but also save huge waste of resources to contain pandemic by a small percentage of contagious individuals.