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

基于智能手机的淋病奈瑟菌即时检测

• 批准号: 10011617
• 负责人: Andrew Slator Paterson
• 金额: $ 25.21万
• 依托单位: LUMINOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011617
• 关键词: Affect; African American; Alabama; Antibiotics; Antigens; Archives; Bedside Testings; Biological Assay; Biology; Biomedical Engineering; Cellular Phone; Chlamydia trachomatis; Clinic; Clinic Visits; Clinical; Clinical Research; Clinical Sensitivity; Collection; Computer software; County; Custom; Data; Detection; Development; Diagnostic; Diagnostics Research; Early treatment; Ectopic Pregnancy; Evaluation; GTP-Binding Protein alpha Subunits, Gs; Genital system; Genome; Goals; Gonorrhea; Health Personnel; High Prevalence; Home environment; Human; Immunoassay; Incidence; Individual; Infection; Infertility; Label; Lateral; Light; Medical; Methods; Monoclonal Antibodies; Multi-Drug Resistance; Multi-Institutional Clinical Trial; Neisseria gonorrhoeae; Nucleic Acid Amplification Tests; Optics; Outcome; Partner Notification; Pelvic Inflammatory Disease; Performance; Phase; Physicians; Prevalence; Probability; Process; Production; Public Health; Publishing; Reporter; Resources; Risk; Sampling; Schedule; Sensitivity and Specificity; Sexual Health; Sexually Transmitted Diseases; Software Engineering; Source; Specificity; Specimen; Swab; Symptoms; Technology; Testing; Time; Training; Universities; Vagina; Validation; Vendor; Woman; Work; base; chronic pelvic pain; cost; cross reactivity; design; disease transmission; high risk; high risk population; improved; innovation; iterative design; luminescence; meetings; men; men who have sex with men; mobile application; nanoparticle; penis; point of care; programs; prospective; prototype; rectal; research clinical testing; screening; sensor; social stigma; success; transmission process; usability; user-friendly; waiver

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.

抽象的 该项目的最终目标是 CLIP-G，这是一种经 FDA 批准和 CE 标记的基于智能手机的测试（≤30 分钟） 用于女性和男性的淋病奈瑟菌 (NG) 检测，用于非处方药 (OTC) 和点药店 护理 (POC) 设置。 NG 导致第二常见的细菌性性传播感染 (STI)，超过 美国每年新增病例 55 万例。未经治疗的个体存在严重后遗症（包括骨盆）的高风险 炎症性疾病、宫外孕和不孕症。大多数 NG 感染可以用抗生素治愈，但 事实上，它们在大多数感染者中不会引起任何症状或非特异性症状，因此需要准确的 测试方法。目前推荐的核酸扩增测试 (NAAT) 价格昂贵且具有 周转时间慢；这限制了它们扩大测试覆盖范围的适用性。快速 POC 测试可以遏制 通过在单个诊所中启用“测试和治疗”方法并立即通知合作伙伴来传播疾病 访问。也可在 POC 环境中使用的 OTC 测试将把测试范围扩大到不具备检测能力的高危个体。 由于性传播感染的耻辱，目前正在寻求检测。 CLIP-G 使用“纳米磷光体”——持久发光 无机纳米颗粒——作为 NG 特异性抗原免疫测定中的侧流测定 (LFA) 报告基因 与智能手机的闪光灯和相机以及廉价的读出适配器相结合。 CLIP平台 与传统的 LFA 相比，可以实现更好的数量级检测限。当前基于抗原的检测 NG 具有高度特异性，但由于其检测限 (LOD) 高，临床敏感性较差。中央 该项目的假设是，与现有的 NG 相比，CLIP-G 免疫测定的 LOD 大大提高 与 NAAT 相比，免疫测定的临床灵敏度 >90%，且不影响高灵敏度 特异性（>98%）。在这个快速通道项目的第一阶段，我们将开发“v1 CLIP-G”台式原型 使用传代培养的临床 NG 进行灵敏且特异的 NG 检测并评估初步分析包容性 隔离；我们还将评估 v1 CLIP-G 原型在小 N 回顾性临床中的临床可行性 学习。假设我们能够在第一阶段获得项目中心假设的初步验证，我们将采取行动 进入第二阶段，我们将首先迭代设计和开发辅助硬件和软件组件 围绕 I 期开发的检测完全集成的 CLIP-G 试剂盒。由此开发的 CLIP-G 套件将 在可用性研究、综合分析性能研究和大型 (n >1,000) 临床研究中进行评估 使用前瞻性收集的标本进行研究。 Luminostics 组建了一支由生物工程师、化学家、 软件工程师、微生物学家、临床医生和制造专家最大限度地提高成功几率。这 该快速通道项目的预期成果是显着降低针对 FDA 510(k) 的最终试验的风险 CLIP-G 的 OTC 审批以及纳米磷-LFA 作为平台技术的进一步验证 在各种可以使用更灵敏的 POC 测试的医疗条件下的潜在应用。