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

项目总结 NanoPin正在推进活动性结核病(TB)的诊断，以解决关键的未得到满足的临床需求 其创新和对患者的潜在影响已被FDA指定为突破性设备。 这种设备将在全球抗击结核病的努力中具有极高的价值，结核病现在是导致死亡的主要原因 传染病，估计每年新增结核病病例1000万例，与结核病相关的死亡150万例。钥匙 尚未满足的结核病诊断需求包括一种既不需要培养也不需要痰的可操作的快速检测方法 和信息，特别是在潜伏性结核病发病率较高的国家，可以准确地检测肺结核病和 肺外结核病，可以在整个患者范围内检测到，包括幼儿和艾滋病毒- 混合感染的病人。NanoPin的高灵敏度诊断平台快速检测特定物种的结核病抗原 直接从血样中提取。我们的技术与目前所有方法的不同之处在于，我们可以检测结核病 不管它在身体的什么地方，也不管它在谁的身体里。我们可以从肺、肾、脑中检测出结核病 而在整个身体中，即使目前的“黄金标准”不能。我们可以在困难的人群中检测到 包括幼儿，甚至婴儿和艾滋病毒混合感染者，所有这些在市场上都得到了很差的服务， 常规的化痰方法不可行的地方。最终，这项技术将使医疗保健 供应商最终缓解了持久的结核病流行。 成功完成这项提议的结果将把我们的结核病诊断设备引入 并通过评估其在井中的性能，使其在诊所和医院可供常规使用- 在多个知名医疗中心进行的结构化临床研究。我们提出了四个具体目标：1)。表演，表演 纳米结核分析试剂盒和多个LC-MS平台的分析验证。在启动临床研究之前， 我们将根据CLSI C62确定结核病检测试剂盒的关键量化值，包括LOD、LOQ和CUT-值。 答：我们将建立多个LC-MS平台，用于临床研究和监管批准，这将进一步推动我们的 商业化程度；2)。应用纳米结核诊断试剂盒检测活动性结核的临床研究 工具包。在这一目标中提出的临床研究将成为510k向fda申请监管的基础。 NanoDetect-TB设备的批准和营销。这些研究将纳入疑似结核病的患者。 并用我们的结核分枝杆菌检测方法和初步的AFB-培养参考法进行分析；若要与 FDA对临床研究和510k提交的指导。与FDA的互动将指导高效和 成功实施了拟议的工作。这一目标的结果是FDA批准了 通过De Novo途径的NanoDetectTB设备；以及4)。扩大儿科中心性和中枢性的临床研究 资源有限，关注重点。我们将进一步评估关键的儿科队列，并解决样本方面的挑战 在资源有限的地区收集和处理托运，以确保我们的应用可以扩展 给所有的病人。

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.