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 platformto develop a rapid smartphone-based point-of-care (POC) diagnostic for the detection of SARS-CoV-2 antigensfrom respiratory specimens. Luminostics' CLIP technology enables high-sensitivity lateral flow immunoassays(LFAs) using proprietary "nanophosphors" in combination with consumer smartphone optics and advanced signalprocessing algorithms for readout. As there is an immediate need for validated tools for rapid POC detection ofactive COVID-19 disease, this project will expeditiously adapt CLIP technology for detection of SARS-CoV-2antigens. While nucleic acid amplification tests (NAATs) have high accuracy, they can take days to return aresult, increasing the potential for continued transmission. In addition, most NAATs must be processed in alaboratory setting using expensive equipment. POC tests approved under the FDA's emergency useauthorization (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 testfor the detection of active COVID-19 infection based on an ultrasensitive immunoassay for SARS-CoV-2antigens in respiratory samples, including remnant viral transport media (VTM), nasopharyngeal/nasal swabs,nasal aspirate, saliva, and sputum. When used as labels in LFAs, Luminostics' patented persistent luminescentinorganic nanophosphors enable orders-of-magnitude lower limits of detection (LODs)-and therefore higherclinical sensitivities-on the CLIP platform compared to traditional visually-read LFAs, using only a smartphone'soptics, 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 CLIPplatform has been previously optimized to detect bacterial and viral pathogens has returned-for our Chlamydiatest-a clinical sensitivity of ~90%, specificity of 99%, and room temperature-stability for >15 months, enablingthe easy transport, storage, and stockpiling of test kits. This project seeks to develop, validate, and obtain FDAEUA for a CLIP-COVID diagnostic test through the following aims: 1) Screening of a large number of mAbs forspecific binding to SARS-CoV-2 antigens and selection of 2-3 preferred sandwich mAb pairs; 2) Developmentand optimization of CLIP-COVID components, including assay design, buffer/conjugate chemistry, and otherancillary 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-19detection with FDA EUA submission completed within 6 months of project initiation.