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 smartphones 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 projects central hypothesis in Phase I, we will move on to Phase II, in which well 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.
Public Health Relevance Statement: NARRATIVE The lack of an accurate, inexpensive and rapid test for gonorrhea in point-of-care (POC) and over-the- counter (OTC) settings represents a significant obstacle to managing the public health burden of this infertility-causing sexually transmitted infection that disproportionately affects women, men who have sex with men, and African- Americans. The opportunistic screening of high-risk populations using highly sensitive POC and OTC tests presents the best chance of reducing its prevalence. In this Fast-Track project, Luminostics will develop a rapid smartphone-based test for gonorrhea detection in women and men designed to give at-home users as well as physicians/minimally trained healthcare workers an unambiguous positive or negative result from non- invasive samples in less than 30 minutes.
Project Terms: Affect; African American; Alabama; Antibiotics; Antigens; Archives; base; Bedside Testings; Biological Assay; Biology; Biomedical Engineering; Cellular Phone; Chlamydia trachomatis; chronic pelvic pain; Clinic; Clinic Visits; Clinical; Clinical Research; Clinical Sensitivity; Collection; Computer software; cost; County; cross reactivity; Custom; Data; design; Detection; Development; Diagnostic; Diagnostics Research; disease transmission; Early treatment; Ectopic Pregnancy; Evaluation; Genital system; Genome; Goals; Gonorrhea; GTP-Binding Protein alpha Subunits, Gs; Health Personnel; High Prevalence; high risk; high risk population; Home environment; Human; Immunoassay; improved; Incidence; Individual; Infection; Infertility; innovation; iterative design; Label; Lateral; Light; luminescence; Medical; meetings; men; men who have sex with men; Methods; mobile application; Monoclonal Antibodies; Multi-Drug Resistance; Multi-Institutional Clinical Trial; nanoparticle; Neisseria gonorrhoeae; Nucleic Acid Amplification Tests; Optics; Outcome; Partner Notification; Pelvic Inflammatory Disease; penis; Performance; Phase; Physicians; point of care; Prevalence; Probability; Process; Production; programs; prospective; prototype; Public Health; Publishing; rectal; Reporter; research clinical testing; Resources; Risk; Sampling; Schedule; screening; Sensitivity and Specificity; sensor; Sexual Health; Sexually Transmitted Diseases; social stigma; Software Engineering; Source; Specificity; Specimen; success; Swab; Symptoms; Technology; Testing; Time; Training; transmission process; Universities; usability; user-friendly; Vagina; Validation; Vendor; waiver; Woman; Work
