A smartphone-enabled point of care HCV Ag diagnostics to reduce HCV-related health disparities

项目总结 丙型肝炎病毒(丙型肝炎病毒)感染是当前全球健康负担，据估计，全球更多 超过5800万人患有慢性丙型肝炎，每年约有150万新感染病例。如果离开 未经治疗的丙型肝炎病毒感染可能导致肝硬变和肝细胞癌。尽管最近有很大的 在开发高效和负担得起的丙型肝炎治疗方法方面取得了进展，这是 丙型肝炎病毒感染管理是对活动性丙型肝炎病毒感染的快速和早期诊断，特别是对那些资源丰富的人。 有限的设置。在世界范围内，只有21%的丙型肝炎病毒感染者得到了诊断。特别值得关注的是 美国印第安人和阿拉斯加土著(AI/AN)不成比例地感染新的丙型肝炎病毒感染率 非裔美国人为2.9例/10万人，非裔美国人为0.5例/10万人和1.2例/10万人 西班牙裔白人的死亡率明显高于非AI/AN族裔和种族群体。 先进行丙型肝炎病毒抗体检测，然后进行确诊的丙型肝炎病毒核糖核酸检测的两步检测流程如下 昂贵、耗时和不理想，这导致感染丙型肝炎病毒的人显著减少 在接受治疗之前从丙型肝炎病毒管理的级联中解脱出来。丙型肝炎病毒抗体检测不能用于 由于不能区分消解型丙型肝炎病毒(R-丙型肝炎病毒)和病毒型丙型肝炎病毒(V- 丙型肝炎病毒)。目前可用的丙型肝炎病毒核糖核酸检测方法，包括POC丙型肝炎病毒核糖核酸检测，仍然是以实验室为基础的。 而且价格昂贵，可能在大多数资源有限的环境中和那些与丙型肝炎病毒相关的健康状况下不可用 差异包括AIS/ANS。低成本、快速、敏感和特异的POC丙型肝炎病毒抗原检测是一种有吸引力的方法 另一种方法，为一步筛查和诊断丙型肝炎病毒提供了极大的希望。目前没有 市面上可买到FDA批准的POC丙型肝炎病毒抗原检测设备。已研制出的丙型肝炎病毒抗原 化验是以实验室为基础的，相对昂贵，更重要的是灵敏度/特异性不够高。 当检测与临床相关的低病毒载量(&lt；1000IU/mL)的样本时，这限制了他们的临床 公用事业。用丙型肝炎病毒血清检测Abbott Architect HCVcAg的敏感性为64.7%-81.9% 病毒载量为104IU/毫升的样本，与病毒载量为1000IU/毫升的丙型肝炎病毒血清样本进行检测时，病毒载量为0.0%-19.7% 病毒载量。因此，为了增加获得丙型肝炎病毒护理的机会，特别是那些受到不成比例影响的人，如 因此，迫切需要廉价、快速、灵敏、特异的丙型肝炎病毒抗原诊断。 测试。这个跨学科项目的主要目标是开发一个基于智能手机的诊断系统 用指纹量快速(30分钟)和灵敏(LOD为200IU/mL到1000IU/mL)检测丙型肝炎病毒 (&lt；100µL)全血样本放置在廉价(&lt；2美元材料成本)、一次性和大量- 可生产的基于微流控技术的墨盒。我们将用感染丙型肝炎病毒的患者的血液来验证所提出的装置 从AIS/ANS收集的样本。

PROJECT SUMMARY Infection due to Hepatitis C virus (HCV) is a current global health burden and is estimated that globally more than 58 million people have chronic HCV with about 1.5 million new infections occurring per year. If left untreated HCV infection can lead to cirrhosis and hepatocellular carcinoma. Despite significant recent advances in the development of highly effective and affordable HCV treatment, one of the major challenges in HCV infection management is rapid and early diagnosis of active HCV infection particularly those in resource- limited settings. Worldwide, only 21% of HCV-infected people are diagnosed. Of particular interest are the American Indians and Alaska Natives (AI/AN) who are disproportionally affected with new HCV infection rate of 2.9 cases/100,000 as compared to 0.5 cases/100,000 in African Americans and 1.2 cases/100,000 in non- Hispanic Whites with significantly higher mortality rates compared to non-AI/AN ethnic and racial groups. The two-step HCV testing process of HCV antibody testing followed by confirmatory HCV RNA testing is expensive, time-consuming, and suboptimal, which has led to significant drop out of HCV-infected individuals from the cascade of HCV management before receiving care. The HCV antibody testing cannot be used for detecting active infection due to its inability to distinguish between resolved HCV (R-HCV) and viremic HCV (V- HCV). The currently available HCV RNA testing assays including the POC HCV RNA assays are still lab-based and expensive and may not be available in most resource-limited settings and those with HCV-related health disparities including AIs/ANs. Low-cost, rapid, sensitive, and specific POC HCV antigen testing is an attractive alternative approach that holds great promise for one-step HCV screening and diagnosis. There is currently no commercially available and FDA-approved POC HCV Ag testing device. The already developed HCV Ag assays are lab-based, relatively expensive, and more importantly not sensitive/specific enough particularly when tested with samples with clinically relevant low viral loads (<1000 IU/mL), which has limited their clinical utilities. The Abbott Architect HCVcAg assay had a sensitivity of 64.7%-81.9% when tested with HCV serum samples with <104 IU/mL viral loads and 0.0%-19.7% when tested with HCV serum samples with <1000 IU/mL viral loads. Therefore, to increase access to HCV care particularly those disproportionally affected such as AIs/ANs, there is an urgent need for inexpensive, rapid, sensitive, and specific POC HCV Ag diagnostic testing. The main goal of this interdisciplinary project is developing a smartphone-based diagnostic system for rapid (<30 minutes) and sensitive (LoD of 200 IU/mL to 1000 IU/mL) HCV detection using fingerprick volume (<100 µL) of a whole blood sample placed on an inexpensive (<$2 material cost), disposable, and mass- producible microfluidic-based cartridge. We will validate the proposed device with HCV-infected patient blood samples collected from AIs/ANs.