A smartphone-based point-of-care test for detection of Neisseria gonorrhoeae

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ABSTRACT The ultimate goal of this project is CLIP-G, an FDA-cleared and CE-marked smartphone-based test (≤30 min) for Neisseria gonorrhoeae (NG) detection in women and men for use in over-the-counter (OTC) and point-of- care (POC) settings. NG causes the 2nd-most common bacterial sexually transmitted infection (STI) with over 550,000 new cases in the US annually. Untreated individuals are at high risk of serious sequelae including pelvic inflammatory disease, ectopic pregnancy, and infertility. Most NG infections are curable with antibiotics, but the fact that they cause no symptoms or non-specific symptoms in a majority of those infected necessitates accurate testing methods. Currently recommended Nucleic Acid Amplification Tests (NAATs) are expensive and have slow turnaround times; this limits their applicability for expanding testing coverage. Rapid POC tests can curb disease transmission by enabling a "test and treat" approach and immediate partner notification in a single clinic visit. An OTC test that can also be used in POC settings will expand testing to the at-risk individuals who do not currently seek testing due to the stigma around STIs. CLIP-G uses "nanophosphors" – persistent luminescent inorganic nanoparticles – as lateral flow assay (LFA) reporters in an immunoassay for NG-specific antigens in combination with a smartphone’s flash and camera and an inexpensive adapter for readout. The CLIP platform enables orders-of-magnitude better detection limits compared to traditional LFAs. Current antigen-based assays for NG are highly specific but have poor clinical sensitivity due to their high limit of detection (LOD). The central hypothesis of this project is that the vastly improved LOD of the CLIP-G immunoassay compared to existing NG immunoassays will result in clinical sensitivities >90% compared to NAATs without compromising on high specificity (>98%). In Phase I of this Fast-Track project, we will develop “v1 CLIP-G” benchtop prototypes for sensitive and specific NG detection and evaluate preliminary analytical inclusivity using sub-cultured clinical NG isolates; we will also evaluate the clinical feasibility of v1 CLIP-G prototypes in a small-N retrospective clinical study. Assuming we can obtain preliminary validation of the project’s central hypothesis in Phase I, we will move on to Phase II, in which we’ll first iteratively design and develop the ancillary hardware and software components of the fully integrated CLIP-G kit around the Phase I-developed assay. Thus-developed CLIP-G kits will be evaluated in usability studies, comprehensive analytical performance studies, and a large (n >1,000) clinical study using prospectively collected specimens. Luminostics has assembled a team of bioengineers, chemists, software engineers, microbiologists, clinicians, and manufacturing experts to maximize the odds of success. The expected outcome of this Fast-Track project is the significant de-risking of the final trial targeting FDA 510(k) OTC clearance for CLIP-G and the further validation of nanophosphor-LFAs as a platform technology with potential applications in a variety of medical conditions that could use more sensitive POC tests.