A smartphone-based rapid point-of-care test for SARS-CoV-2 detection from respiratory samples

Abstract In this Emergency Supplemental project, Luminostics will leverage our de-risked and scale-ready CLIP platform to develop a rapid smartphone-based point-of-care (POC) diagnostic for the detection of SARS-CoV-2 antigens from respiratory specimens. Luminosticsandapos; CLIP technology enables high-sensitivity lateral flow immunoassays (LFAs) using proprietary “nanophosphors” in combination with consumer smartphone optics and advanced signal processing algorithms for readout. As there is an immediate need for validated tools for rapid POC detection of active COVID-19 disease, this project will expeditiously adapt CLIP technology for detection of SARS-CoV-2 antigens. While nucleic acid amplification tests (NAATs) have high accuracy, they can take days to return a result, increasing the potential for continued transmission. In addition, most NAATs must be processed in a laboratory setting using expensive equipment. POC tests approved under the FDAandapos;s emergency use authorization (EUA) for COVID-19 also require the purchase of specialized equipment, limiting widespread use. Thus, this project will develop, validate, and obtain FDA EUA for CLIP-COVID, a rapid smartphone-based test for the detection of active COVID-19 infection based on an ultrasensitive immunoassay for SARS-CoV-2 antigens in respiratory samples, including remnant viral transport media (VTM), nasopharyngeal/nasal swabs, nasal aspirate, saliva, and sputum. When used as labels in LFAs, Luminosticsandapos; patented persistent luminescent inorganic nanophosphors enable orders-of-magnitude lower limits of detection (LODs)—and therefore higher clinical sensitivities—on the CLIP platform compared to traditional visually-read LFAs, using only a smartphoneandapos;s optics, paired with an inexpensive adapter and mobile app, for unambiguous readout. The assay will use high- affinity monoclonal antibodies (mAbs) specific to SARS-CoV-2 antigens as diagnostic reagents. The CLIP platform has been previously optimized to detect bacterial and viral pathogens has returned—for our Chlamydia test—a clinical sensitivity of ~90%, specificity of 99%, and room temperature-stability for andgt;15 months, enabling the easy transport, storage, and stockpiling of test kits. This project seeks to develop, validate, and obtain FDA EUA for a CLIP-COVID diagnostic test through the following aims: 1) Screening of a large number of mAbs for specific binding to SARS-CoV-2 antigens and selection of 2–3 preferred sandwich mAb pairs; 2) Development and optimization of CLIP-COVID components, including assay design, buffer/conjugate chemistry, and other ancillary components; and 3) Analytical/clinical validation studies, manufacturing transfer, and EUA submission. The expected outcome of this project is an affordable, shelf-stable, rapid, user-friendly test for POC COVID-19 detection with FDA EUA submission completed within 6 months of project initiation.Narrative While over 2 million cases of SARS-CoV-2 have now been confirmed worldwide, many sources suggest that the true number of positive cases may be much higher, as healthcare systems worldwide have struggled to effectively monitor, diagnose, and report cases in a timely manner. This has limited the ability to track transmission in real time, and accurately estimate the number of cases that will require treatment, and effectively allocate healthcare resources accordingly. The proposed project will result in an affordable, shelf-stable, 15-min POC test for COVID-19 that will enable more widespread testing, helping to combat transmission and better track disease dynamics.