Rapid point-of-care test for hepatitis C virus (HCV) core antigen to screen active HCV infection

项目总结/摘要 在过去的十年中，丙型肝炎病毒（HCV）检测呈阳性的人数显著增加 年轻人感染病毒的情况也越来越普遍。现在，大约有50,000个感染者 预计每年都有40%的人没有意识到他们的感染。尽管，其中大约有一半 急性感染可以由个人清除，其余的将成为慢性感染。如果丙型肝炎是 如果未得到诊断和治疗，可能会发生严重的肝损伤和死亡。HCV相关的肝损害是 现在是美国的主要死因，每年夺去约15，000人的生命。虽然没有HCV疫苗， 目前，确实存在有效的抗逆转录病毒疗法，治愈率超过95%。 因此，识别丙型肝炎（慢性感染）患者是治疗和阻止HCV传播的关键任务。 目前，筛查和诊断活动性HCV感染需要两种测试。一个抗体测试，以确定 既往暴露和一次核酸检测（NAT）以确认活动性感染。然而，这两步程序 是繁琐的，严重依赖于临床实验室;此外，抗体在第一次检测中不敏感， 两个月的新的HCV感染和错过这些案件。因此，目前的测试程序已成为 丙型肝炎筛查的瓶颈 除了目前的两步法，HCV核心抗原（cAg）检测已被提出作为一种同样有效的方法。 用于筛查和诊断活动性HCV感染的方法。自2000年以来，许多临床研究 研究表明，高灵敏度的cAg检测可与NAT一样有效地用于筛查活动性HCV感染。 然而，目前所有可用的HCV cAg检测只能在实验室环境中进行，并且需要经过培训 操作和维护人员。因此，本第一阶段项目拟展示 开发一种高灵敏度的cAg检测的可行性，该检测可以在 通过利用基于现有血糖仪（BGM）硬件的检测平台和 一次性微流体测定盒。今天的BGM是几十年研发的结晶，专为小型 占地面积小，操作简单，成本低，可规模化生产。利用BGM技术和熟悉的 新应用的分析格式使我们能够降低与设备开发相关的风险和成本 和扩大生产。最终产品将是一个POC系统，由基于BGM的仪表和 用于测量高危个体中cAg水平的HCV cAg一次性检测盒。新的POC HCV cAg检测 将能够快速识别患有慢性HCV感染的个体，并允许早期治愈性治疗。的 拟议的产品也将大大有利于发展中国家的高HCV流行率，但缺乏测试 基础设施演进 该项目将包括三个发展目标，包括1）开发和优化高灵敏度的cAg 使用BGM平台进行测试; 2）验证生物样品中基于BGM的cAg测试;以及3）整合 用现有的原型系统优化测定。

Project Summary / Abstract The number of people testing positive for hepatitis C virus (HCV) has increased significantly in the last decade and younger adults contracting the virus has become more common. Now, roughly 50,000 infections are expected each year and about 40% of the people are not aware of their infections. Although, about half of these acute infections can be cleared by the individual, the remainder will become chronically infected. If hepatitis C is undiagnosed and remains untreated, severe liver damage and death can occur. HCV related liver damage is now a leading cause of death in the U.S., claiming ~15,000 lives annually. Although no vaccine for HCV is currently available, effective anti-retroviral treatment does exist to treat the disease with over 95% cure rate. Hence, identifying people with hepatitis C (chronic infection) is a critical task to treat and stop the spread of HCV. Currently, screening and diagnosing active HCV infection requires two tests. One antibody test to determine prior exposure and one nucleic acid test (NAT) to confirm an active infection. However, this two-step procedure is cumbersome and heavily relies on clinical laboratories; additionally, the antibody is not sensitive in the first two months of a new HCV infection and missing these cases. Hence, the current testing procedure has become the bottleneck for screening hepatitis C. Besides the current two-step approach, HCV core antigen (cAg) test has been proposed as an equally effective approach for screening and diagnosing active HCV infections. Numerous clinical studies since the 2000s have demonstrated a highly sensitive cAg test can be used to screen active HCV infection as effectively as NAT. However, all currently available HCV cAg test can only be performed in a laboratory setting and require trained personnel for operation and maintenance. As a result, this Phase I project is proposed to demonstrate the feasibility of developing a highly sensitive cAg test that can be performed quickly and accurately at the point-of- care (POC) by utilizing a detection platform based on the existing Blood Glucose Meter (BGM) hardware and a disposable microfluidic assay cartridge. Today’s BGM is the culmination of decades of R&D, designed for small footprint, simple operation, low cost and large-scale production. Leveraging the BGM technology with a familiar assay format for new applications allows us to reduce the risk and costs associated with device development and scale-up production. The final product will be a POC system composed of a BGM based meter and disposable cartridges for HCV cAg for measuring cAg levels in high risk individuals. The new POC HCV cAg test will be able to quickly identify individuals with chronic HCV infection and allow early curative treatment. The proposed product will also greatly benefit developing countries with high HCV prevalence but lacking testing infrastructure. The project will include three development goals, including 1) develop and optimize a highly sensitive cAg test using the BGM platform; 2) validate the BGM based cAg test in biological samples; and 3) integrating the optimized assay with an existing prototype system.