Vastly improved influenza diagnostics through the development of a handheld thermal contrast reader

VIGILANT DIAGNOSTICS NIAID/NIH STTR Phase I Application Vastly improved influenza diagnostics through the development of a portable thermal contrast reader PROJECT SUMMARY/ABSTRACT Despite recent advances in rapid influenza diagnostic tests, false negatives stemming from poor sensitivity contribute to nosocomial transmission and prevent thousands from receiving appropriate antiviral treatment. Among vulnerable populations, the consequences can be grave. The population under five years of age experienced hospitalization rates of 46.9/100,000, with 96 influenza-associated pediatric deaths during the 2013- 2014 influenza season and 348 deaths in the 2009 pandemic. Influenza-associated hospitalization rates were 54.3/100,000 for those 50-64 years and 88.1/100,000 for those over 65 years. We have developed a desktop system that uses a thermal contrast assay (TCA) reader to detect gold nanoparticles used in nearly all lateral flow assays (LFAs) for influenza. With this TCA reader, we have demonstrated an 8-fold improvement in sensitivity over results from the industry-leading handheld BD Veritor? system in a flu A antigen dilution study. We propose to begin commercializing this TCA reader technology by 1) Building a prototype portable TCA reader that is functionally equivalent to the existing desktop TCA reader and 2) Testing this prototype portable TCA reader alongside an existing visual flu LFA (i.e. BD Veritor? or other) system, the desktop TCA reader, and polymerase chain reaction (PCR) testing in a clinical setting. To build a prototype of the portable TCA reader, we will first test and validate new (and cheaper) handheld components for functional equivalency with the corresponding fully characterized component in the desktop TCA reader. We will then assemble the parts with a custom-designed LFA holder into a functioning portable TCA reader. Further, we will work to develop proprietary Windows based software and algorithms for control of the prototype. The prototype TCA reader will be tested on up to 400 discarded influenza LFAs. We will also compare to the corresponding nasopharyngeal samples that generated the LFAs to allow for correlative ?gold standard? PCR testing. The visual results of these LFAs will be known. We will then test the visually negative LFAs with the portable TCR reader prototype. After the corresponding nasopharyngeal swabs undergo PCR testing, all results will be compared. This portable TCA reader system will then be a prototype for a low-cost, high-sensitivity, easy-to-use point- of-care influenza diagnostic system that will reduce false negatives over today?s industry-leading handheld BD Veritor? and other visual based flu LFAs.