RAPID:Antibody-Based Nanoplasmonic Barcode Biosensors for COVID-19 Detection

最近几周和几个月，COVID-19的出现成为全球范围内健康的重大威胁。与这种疾病作斗争的一个主要挑战是缺乏快速诊断设备。虽然目前的检测很灵敏，但它们需要配备特殊设备的实验室，并且可能需要几天才能提供结果。该项目旨在识别和验证抗体，以用于实时、即时护理的COVID-19生物传感器设备。这种设备可以让医生和其他医疗保健专业人员立即诊断出受感染的人，并为他们提供所需的治疗，同时更有效地遏制这种流行病的传播。SARS-CoV-2是COVID-19疾病的病毒病因。一种基于抗体的纳米等离子体条形码生物传感器可以提供实时、即时的诊断设备。本项目将开发这样一种传感器。第一个目标是发现SARS-CoV-2结合抗体。为了确保鉴定出的抗体具有足够的多样性，将寻求三个平行的发现途径：1)鉴定与SARS-CoV-2和MERS-CoV刺突蛋白交叉反应的抗体，2)抗SARS-CoV-1抗体结合SARS-CoV-2的合理工程设计，以及3)新型SARS-CoV-2抗体的从头设计。将从通过三种互补方法发现的抗体中选择约四对抗体。根据ELISA和表面等离子体共振测量的亲和力，以及竞争ELISA监测的它们与独特表位结合的选择性，这些对将用于SARS-CoV-2检测。最后，抗体对将用于SARS-CoV-2纳米等离子体生物传感器的设计和评价。纳米粒子信号只有在病毒存在的情况下才会被生物传感器检测到。与目前的诊断测试相比，拟议的研究将能够更快地检测到SARS-CoV-2，从而更好地了解其传播并更有效地遏制疫情。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Recent weeks and months have seen the emergence of COVID-19 as a major threat to health on a global scale. One major challenge associated with combating this disease is the lack of a rapid diagnostic device. Although current tests are sensitive, they require specially equipped laboratories and can take several days to provide results. This project aims to identify and validate antibodies for use in real-time, point-of-care, COVID-19 biosensor devices. Such devices could allow doctors and other healthcare professionals to immediately diagnose infected individuals and get them the treatment they need while more effectively containing the spread of this pandemic.SARS-CoV-2 is the viral cause of the COVID-19 illness. An antibody-based nanoplasmonic barcode biosensor could a provide real-time, point-of-care diagnostic device. This project will develop such a sensor. The first objective is the discovery of SARS-CoV-2 binding antibodies. To ensure a sufficient diversity of antibodies are identified, three parallel discovery pathways will be pursued: 1) the identification of antibodies that cross-react with SARS-CoV-2 and MERS-CoV spike proteins, 2) the rational engineering of anti- SARS-CoV-1 antibodies to bind SARS-CoV-2, and 3) the in silico, de novo design of novel SARS-CoV-2 antibodies. About four antibody pairs will be selected from the antibodies discovered through the three complementary approaches. The pairs will be used for SARS-CoV-2 detection on the basis of their affinity measured by ELISA and surface plasmon resonance and of the selectivity of their binding to unique epitopes, as monitored by competition ELISA. Finally, the antibody pairs will be used in the design and evaluation of SARS-CoV-2 nanoplasmonic biosensors. Nanoparticle signals will only be detected by the biosensors in the presence of virus. The proposed research will enable the more rapid detection of SARS-CoV-2 compared to current diagnostic tests, resulting in a better understanding of its spread and more effective containment.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.