Rapid detection of infectious viral particles by cluster induced exhaustive reaction

通过簇诱导穷举反应快速检测感染性病毒颗粒

• 批准号: 10443877
• 负责人: Jun Wang
• 金额: $ 23.59万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-02 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10443877
• 关键词: 2019-nCoV; Address; Aerosols; Affinity; Air; American; Antibodies; Antigens; Binding; Biological Assay; Blood; Breathing; COVID-19; COVID-19 detection; COVID-19 pandemic; Cessation of life; Communicable Diseases; Communities; Coronavirus; Coughing; Deposition; Detection; Devices; Diagnosis; Diagnostic Equipment; Ensure; Environment; Enzyme-Linked Immunosorbent Assay; Epitopes; Evaluation; Exhalation; Exhibits; Goals; Gold; Government; Health; Horseradish Peroxidase; Hospitals; Human; Immigration; Immunoglobulin G; Immunoglobulin M; Individual; Infection; Length; Life; Lifting; Location; Measures; Methods; Nebulizer; Paper; Patients; Persons; Policies; Polymerase Chain Reaction; Population; Rapid diagnostics; Reaction; Recording of previous events; Resources; Safety; Sampling; Sensitivity and Specificity; Signal Transduction; Site; Sneezing; Societies; Specificity; Speed; Spottings; Surface; Symptoms; Tannic Acid; Techniques; Technology; Testing; Time; Variant; Viral; Virion; Virus; Visualization; base; clinical diagnosis; cost; design; detection limit; diagnostic technologies; diagnostic tool; exhaustion; flu; influenzavirus; innovation; instrument; multiplex detection; nanoparticle; pandemic disease; particle; pathogen; rapid detection; rapid test; reconstitution; respiratory aerosol; respiratory virus; screening; sensor; transmission process; wasting; young adult

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.

概括 COVID-19 大流行给各国的健康、经济、环境和移民带来了巨大挑战 美国广泛实施了提高诊断能力和限制政策 然而，美国仍有超过20万人死亡，50万人住院。 严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 单独存在时具有高度传染性。 早期感染，尤其是年轻人，在活跃传播病毒时通常不会表现出任何症状 在社区中，通过说话和呼吸这两种传播方式通常会排放大量污染物。 气溶胶中的病毒颗粒数量少于咳嗽和打喷嚏，因此很难检测到。 可用的诊断工具种类较多，目前的现场诊断技术不具备足够的能力 检测感染者排放的气溶胶中少量病毒颗粒的灵敏度和速度。 标准方法、聚合酶链式反应 (PCR) 及其变体仅在实验室环境中具有超灵敏性 检测散发的气溶胶是临床诊断的有吸引力的目标，因为采样。 不具有侵入性，检测结果直接决定一个人是否传播病毒。 针对上述挑战，我们将开发一种基于簇诱导穷举的快速诊断技术 反应（CIER）具有很少的病毒敏感性和成本几分钱的一次性设备，因此这种 纸质设备可以在任何地方经常使用，以在感染者出现之前立即识别他/她 CIER 进一步将 SARS-CoV-2 传播到社区，同时理论上可以无限放大信号。 保持高特异性，因此非常适用于检测 SARS-CoV-2 颗粒，其中只有紧凑的颗粒 抗原簇可以触发 CIER 传感器，提出了两个具体目标：（1）通过构建 CIER 传感器。 组装抗体、间隔基和 HRP 部分，并优化 CIER 的设计以检测 SARS-CoV-2 具有超高灵敏度的病毒颗粒，以及 (2) 快速定量呼吸中和体中的 SARS-CoV-2 病毒颗粒 用于 POC 诊断，并通过多重检测区分流感病毒和 SARS-CoV-2。 革命性诊断技术将具有检测 SARS-CoV-2 的超高灵敏度和特异性 CIER 纸的使用不仅可以降低呼出空气中的病毒，而且成本低廉且易于任何人使用。 立即识别病毒传播者，同时也节省了遏制疫情的巨大资源浪费 传染性个体的比例很小。