Novel disposable microchips for HIV-1 viral load

用于检测 HIV-1 病毒载量的新型一次性微芯片

• 批准号: 8411025
• 负责人: Utkan Demirci
• 金额: $ 44.63万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411025
• 关键词: AIDS/HIV problem; Accounting; Adherence; Anti-Retroviral Agents; Antibodies; Antigens; Biological Assay; Biological Markers; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Cessation of life; Clinical; Communicable Diseases; Complex; Detection; Developed Countries; Developing Countries; Disease Progression; Drug resistance; Electron Microscope; Ensure; Failure; Fingers; Guidelines; HIV; HIV Envelope Protein gp120; HIV-1; Hepatitis; Image; Imaging technology; Individual; Infant; Infection; Influenza; Life; Lymphocyte Count; Malaria; Metals; Microfluidics; Monitor; Morbidity - disease rate; Patients; Persons; Pharmaceutical Preparations; Quality of Care; Quality of life; RNA; RNA-Directed DNA Polymerase; Rural; Sampling; Scanning; Staging; Surface; Surface Plasmon Resonance; Symptoms; System; Technology; Testing; Tuberculosis; Vertical Disease Transmission; Viral Load result; Whole Blood; Work; World Health Organization; antiretroviral therapy; base; cost effective; improved; instrument; microchip; nanoparticle; novel; optical imaging; pandemic disease; point of care; resistant strain; response; tool

DESCRIPTION (provided by applicant): To reduce morbidity and improve quality of life for persons living with HIV/AIDS, the World Health Organization (WHO) is rapidly expanding access to antiretroviral therapy (ART) in developing countries. However, the expansion is significantly restricted by the lack of cost-effective point-of-care (POC) viral load assays that cn effectively reach patients living in rural, isolated settings. In developed countries, HIV-1 viral load is regularly used to closely monitor and assess the patient response to ART, to ensure drug adherence and to stage disease progression. In contrast, developing countries are using CD4+ cell count and clinical symptoms to guide ART following the WHO guidelines with the exception of infants, where viral load assays are required. This is because HIV-1 viral load assays are expensive ($50-200 per test), instrument-dependent, and technically complex. Recent studies, however, have shown that CD4 cell counting strategy cannot detect early virological failure. This failure leads to accumulation of drug-resistant strains in infected individuals and reduces the efficacy of first-line drugs. Thus, a rapid, inexpensive, and simple viral load test is urgently needed at the point of care (POC). Here, microfluidics and optical imaging technologies will be used to create a novel HIV-1 viral load microchip. It was hypothesized that the developed HIV-1 viral load microchip can: (i) selectively capture HIV from whole blood, (ii) be sensitive within the clinical cut-off (with ¿10% error range), inexpensive (<$1), rapid (within 15 minutes), and automated to handle finger-prick whole blood (100 ¿L) to aid in quality care and treatment at the POC. This is a technology driven proposal motivated by the urgent significant clinical need. Prior work has shown the proof-of-concept that HIV-1 can be captured and quantified from patient whole blood on-chip. The following distinct but interrelated specific aims are proposed: Aim 1: To build disposable microchips to capture HIV-1, Aim 2: To develop a portable system for on-chip HIV-1 viral load by integrating HIV-1 capturing microchips with a detection/quantification system, and Aim 3: To validate the microchip technology with 200 HIV-infected samples. This proposed technology is broadly applicable to other infectious diseases having a reasonably well-described biomarker available such as influenza, hepatitis, malaria and tuberculosis. PUBLIC HEALTH RELEVANCE: To reduce morbidity and to improve quality of life for people living with HIV/AIDS, the access to antiretroviral treatment is rapidly expanding in developing countries. However, this expansion is significantly restricted by the lack of cost-effective viral load monitoring tools. To aid in quality care and treatment of people living with HIV/AIDS, we propose a novel HIV viral load microchip, which is: (i) capable of selectively capturing HIV from whole blood, (ii) sensitive within the clinical cut-off (with ¿10%) error range, inexpensive (<$1), rapid (within 15 minutes), and automated to handle finger-prick whole blood (100 ¿L).

说明（由申请人提供）：为了降低发病率和改善艾滋病毒/艾滋病患者的生活质量，世界卫生组织（世卫组织）正在发展中国家迅速扩大获得抗逆转录病毒治疗的机会。然而，由于缺乏具有成本效益的即时护理（POC）病毒载量测定，无法有效地覆盖生活在偏远农村地区的患者，这一扩展受到了严重限制。在发达国家，经常使用HIV-1病毒载量来密切监测和评估患者对抗逆转录病毒治疗的反应，以确保药物依从性和疾病进展分期。相比之下，发展中国家正在使用CD4+细胞计数和临床症状来指导抗逆转录病毒治疗，但婴儿除外，因为婴儿需要进行病毒载量测定。这是因为HIV-1病毒载量检测价格昂贵（每次检测50-200美元），依赖仪器，技术复杂。然而，最近的研究表明，CD4细胞计数策略不能检测早期病毒学失败。这种失败导致耐药菌株在受感染个体中积累，并降低一线药物的疗效。因此，迫切需要在护理点（POC）进行快速、廉价和简单的病毒载量检测。在这里，微流体和光学成像技术将用于创建一个新的HIV-1病毒载量微芯片。假设开发的HIV-1病毒载量微芯片可以：(i)选择性地从全血中捕获HIV， （ii）在临床切断范围内敏感（误差范围为10%），价格低廉（< 1美元），快速（15分钟内），并自动处理手指刺破的全血（100¿L），以帮助POC的高质量护理和治疗。这是一项由迫切的临床需求驱动的技术提案。先前的工作已经证明，可以从芯片上的患者全血中捕获和量化HIV-1。提出了以下不同但相互关联的具体目标：目标1：构建一次性微芯片来捕获HIV-1，目标2：通过将HIV-1捕获微芯片与检测/定量系统集成，开发便携式芯片上HIV-1病毒载量系统，目标3：用200个hiv感染样本验证微芯片技术。这项提议的技术广泛适用于其他具有合理描述的生物标志物的传染病，如流感、肝炎、疟疾和结核病。