Early and accurate diagnosis of pulmonary and extrapulmonary tuberculosis in all patient groups using a circulating pathogen-derived antigen

项目摘要 NanoPin正在推进活动性结核病（TB）的诊断，以解决关键的未满足的临床需求 其创新性和潜在的患者影响已被FDA指定为突破性设备。 这种设备在全球抗击结核病的努力中将非常有价值，结核病现在是导致死亡的主要原因。 传染病，估计每年有1000万新结核病病例和150万结核病相关死亡。关键 尚未满足的结核病诊断需求包括一种快速检测，这种检测既不需要培养，也不需要痰液， 特别是在潜伏性结核病发病率高的国家， 肺外结核，并可以检测整个患者谱，包括幼儿和艾滋病毒- 合并感染的病人NanoPin的高灵敏度诊断平台可快速检测物种特异性结核抗原 直接从血液样本中提取我们的技术与目前所有的方法不同， 不管它在身体的哪个部位，在谁的身体里我们可以在肺、肾、脑中检测出结核病 甚至在目前的“黄金标准”无法做到的情况下。我们可以在困难的群体中发现 包括幼儿，甚至婴儿和艾滋病毒合并感染，所有这些都是在市场上服务差， 传统的痰液检查方法不可行。最终，这项技术将使医疗保健 最终缓解结核病的流行。 成功完成该提案的结果将把我们的结核病诊断设备引入 市场，并通过评估其在井中的性能，使其可用于诊所和医院的日常使用， 在多个知名医疗中心进行结构化临床研究。我们提出了四个具体目标：（1）。执行 NanoTB检测试剂盒和多重LC-MS平台的分析验证。在开始临床研究之前， 我们将根据CLSI C62确定TB检测试剂盒的关键定量值，包括LoD、LoQ和临界值- A.我们将建立多个LC-MS平台用于临床研究和监管批准，这将进一步促进我们的 商业化程度; 2）.开展NanoTB诊断检测试剂盒检测活动性TB的临床研究 套件在这一目标中提出的临床研究将是向FDA申请510 k的基础， NanoDetect-TB设备的批准和上市。这些研究将招募疑似结核病患者 用我们的TB检测法和原代AFB培养参考方法进行分析; 3）.以连通 FDA的临床研究和510 k提交指南。与FDA的互动将指导有效和 顺利开展拟议工作。这一目标的结果是FDA批准了 NanoDetectTB装置通过De Novo途径;和4）.扩展以儿科为中心的临床研究， 资源有限的重点。我们将进一步评估关键儿科队列，并解决样本的挑战 在资源有限的地区收集和处理运输，以确保我们的应用程序可以扩展 所有患者。

PROJECT SUMMARY NanoPin is advancing a diagnostic for active tuberculosis (TB) that addresses critical unmet clinical needs and its innovation and potential patient impact has resulted in designation as a breakthrough device by the FDA. This device will highly valuable in the global effort to combat TB, which is now the leading cause of death from infectious disease, with an estimated 10.0 million new TB cases and 1.5 million TB-related deaths annually. Key unmet needs for TB diagnosis include a rapid test that is both culture-free and non-sputum-based, is actionable and informative especially in countries with high latent TB rates, can accurately detect both pulmonary and extrapulmonary TB, and can detect across the entire patient spectrum including young children and HIV- coinfected patients. NanoPin’s highly sensitive diagnostic platform rapidly detects species-specific TB antigens directly from blood samples. Our technology is differentiated from all current methods in that we can detect TB no matter where it is in the body and whose body it is in. We can detect TB based in the lungs, kidneys, brain and throughout the body, even when the current “gold standard” cannot. We can detect in difficult cohorts including young children and even infants and HIV co-infected, all of which are poorly served in the market and where conventional sputum methods are not feasible. Ultimately, this technology will enable health care providers to finally mitigate the enduring TB epidemic. The outcomes of successful completion of this proposal will introduce our TB diagnostic device into the market and make it available for routine use in clinics and hospitals by evaluating its performance in a well- structured clinical study in multiple high profile medical centers. We propose four specific aims: 1). To perform analytical validation of the NanoTB Assay Kit and Multiple LC-MS Platforms. Prior to initiating clinical studies, we will determine key quantitative values for the TB assay kits including LoD, LoQ, and cut-values per CLSI C62- A. We will establish multiple LC-MS platforms for clinical studies and regulatory approval which will further our commercialization reach; 2). To perform clinical studies for detection of active TB with NanoTB diagnostic assay kits. The clinical studies proposed in this aim will be the basis for 510k application to the FDA for regulatory approval and marketing of the NanoDetect-TB device. The studies will enroll patients suspected of TB disease and analyze with our TB assay and the primary AFB-culture reference method; 3). To communicate with the FDA for guidance for clinical studies and 510k submission. Interactions with the FDA will guide the efficient and successful implementation of the proposed work. The outcome of this aim is the FDA clearance of the NanoDetectTB device via the De Novo pathway; and 4). To extend clinical studies for pediatric centric and resource limited focus. We will further evaluate the critical pediatric cohort and address challenges for sample collection and handling shipping in resource limited regions in order to ensure our application can be extended to all patients.