Rapid detection of infectious viral particles by cluster induced exhaustive reaction

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.