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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要由于丙型肝炎病毒（HCV）引起的感染是目前的全球健康燃烧，据估计，全球范围内更多超过5800万人患有慢性HCV，每年发生约150万个新感染。如果离开未处理的HCV感染会导致肝硬化和肝细胞癌。尽管最近有很多发展高效且负担得起的HCV治疗方面的进步，这是主要挑战之一 HCV感染管理是活跃HCV感染的快速和早期诊断，特别是资源中的HCV感染 - 有限的设置。在全球范围内，只有21％的HCV感染者被诊断出。特别感兴趣的是美国印第安人和阿拉斯加原住民（AI/AN）受到新的HCV感染率不成比例的 2.9案例/100,000，而非洲裔美国人为0.5例/100,000例，非案例/100,000例与非族/种族和种族群体相比，死亡率显着更高的西班牙白人。 HCV抗体测试的两步HCV测试过程，然后进行确认HCV RNA测试是昂贵，耗时和次优的，这导致了HCV感染者的大量辍学在接受护理之前，请从HCV管理级联。 HCV抗体测试不能用于由于无法区分已分辨的HCV（R-HCV）和病毒HCV而引起的活性感染（V-） HCV）。当前可用的HCV RNA测试测定法，包括POC HCV RNA分析仍然是基于实验室的又昂贵，并且可能在大多数资源有限的设置中不可用，并且患有HCV相关的健康包括AIS/ANS在内的差异。低成本，快速，敏感和特定的POC HCV抗原测试是一个吸引人的替代方法对一步HCV筛查和诊断具有巨大的希望。目前没有市售和FDA批准的POC HCV AG测试设备。已经开发的HCV AG 测定是基于实验室的，相对昂贵的，更重要的是尤其不是敏感/特定当用具有临床相关的低病毒载荷（<1000 IU/mL）的样品测试时，该样品限制了临床公用事业。使用HCV串行测试时，Abbott Architect HCVCAG分析的灵敏度为64.7％-81.9％用<104 IU/ml病毒载荷的样品和0.0％-19.7％的样品用<1000 IU/ml的HCV血清样品进行测试时病毒载荷。因此，为了增加获得HCV护理的访问，特别是那些受到不成比例影响的人，例如 AIS/ANS，迫切需要廉价，快速，敏感和特定的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快速（<30分钟）和敏感（LOD为200 IU/ml至1000 IU/ml）HCV检测使用指纹体积（<100 µl）的全血样品，放置在廉价的（<$ 2的材料成本），一次性和质量可生产的基于微流体的墨盒。我们将用HCV感染的患者血液验证所提出的设备从AIS/ANS收集的样品。