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

支持智能手机的 HCV Ag 护理点诊断，可减少与 HCV 相关的健康差异

• 批准号: 10570705
• 负责人: Hadi Shafiee
• 金额: $ 85.4万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570705
• 关键词: Acute Hepatitis C; Affect; African American population; Alaska Native; Algorithms; American Indians; Artificial Intelligence; Biological Assay; Blood specimen; Caring; Cellular Phone; Chemistry; Chronic Hepatitis C; Cirrhosis; Clinical; Consumption; Detection; Development; Development Plans; Devices; Diagnosis; Diagnostic; Diagnostic tests; Drops; Early Diagnosis; Ethnic group; FDA approved; Gases; Generations; Glycerol; Goals; HCV screening; Hemodialysis; Hepatitis C; Hepatitis C Antibodies; Hepatitis C Therapy; Hepatitis C virus; Hydrogen Peroxide; Image; Immunocompromised Host; Incidence; Individual; Infection; Label; Lead; Left; Machine Learning; Magnetism; Microfluidics; Molecular Conformation; Monitor; Native Americans; Not Hispanic or Latino; Pathogen detection; Patients; Persons; Primary carcinoma of the liver cells; Process; Publishing; Race; Resource-limited setting; Sampling; Serum; Surface; Telephone; Testing; Therapeutic immunosuppression; Time; Viral Load result; Virus; Water; Whole Blood; World Health Organization; antigen test; base; clinically relevant; cost; design; diagnostic platform; follow-up; global health; health disparity; improved; infection management; infection rate; interest; microchip; mortality; nanoparticle; nanoprobe; point of care; rapid diagnosis; scale up; smartphone Application; viral RNA; viral detection

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.

项目概要 丙型肝炎病毒 (HCV) 感染是当前的全球健康负担，估计全球范围内更多 超过 5800 万人患有慢性 HCV，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导致肝硬化和肝细胞癌。尽管最近发生了重大 在开发高效且负担得起的丙肝病毒治疗方面取得进展，这是人类面临的主要挑战之一 HCV 感染管理是对活动性 HCV 感染的快速和早期诊断，特别是在资源匮乏的地区。 有限的设置。在全球范围内，只有 21% 的 HCV 感染者得到诊断。特别令人感兴趣的是 美洲印第安人和阿拉斯加原住民 (AI/AN) 受到新 HCV 感染率的影响尤为严重 2.9 例/100,000 例，而非裔美国人为 0.5 例/100,000 例，非裔美国人为 1.2 例/100,000 例 与非 AI/AN 族裔和种族群体相比，西班牙裔白人的死亡率明显更高。 HCV 抗体检测和确认性 HCV RNA 检测的两步 HCV 检测过程是 昂贵、耗时且不理想，导致 HCV 感染者大幅减少 接受护理之前的 HCV 管理级联。 HCV 抗体检测不能用于 由于无法区分已消退的 HCV (R-HCV) 和病毒血症 HCV (V- 丙肝病毒）。目前可用的 HCV RNA 检测方法（包括 POC HCV RNA 检测方法）仍然是基于实验室的 而且价格昂贵，并且在大多数资源有限的环境和患有 HCV 相关健康的环境中可能无法获得 差异，包括 AI/AN。低成本、快速、灵敏、特异的 POC HCV 抗原检测是一种有吸引力的方法 一种为一步式 HCV 筛查和诊断带来巨大希望的替代方法。目前没有 市售且 FDA 批准的 POC HCV Ag 检测设备。已开发的 HCV Ag 测定是基于实验室的，相对昂贵，更重要的是不够灵敏/特异性，特别是 当使用临床相关的低病毒载量（<1000 IU/mL）的样本进行测试时，这限制了其临床 公用事业。使用 HCV 血清进行测试时，Abbott Architect HCVcAg 检测的灵敏度为 64.7%-81.9% 病毒载量 <104 IU/mL 的样品，当使用 <1000 IU/mL 的 HCV 血清样品进行测试时，病毒载量为 0.0%-19.7% 病毒载量。因此，为了增加获得丙肝病毒护理的机会，特别是那些受到不成比例影响的人，例如 AI/AN，迫切需要廉价、快速、灵敏、特异的 POC HCV Ag 诊断 测试。这个跨学科项目的主要目标是开发基于智能手机的诊断系统 使用指尖采血体积快速（<30 分钟）且灵敏（LoD 为 200 IU/mL 至 1000 IU/mL）HCV 检测 (<100 µL) 全血样本放置在廉价（<2 美元材料成本）、一次性、大规模的 可生产的基于微流体的盒。我们将使用 HCV 感染患者的血液验证所提出的装置 从 AI/AN 收集的样本。