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: 8943940
• 负责人: Utkan Demirci
• 金额: $ 41.64万
• 依托单位: STANFORD UNIVERSITY
• 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/8943940
• 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.

描述(由申请人提供)：为了减少艾滋病毒/艾滋病患者的发病率并提高他们的生活质量，世界卫生组织(WHO)正在迅速扩大发展中国家获得抗逆转录病毒疗法(ART)的机会。然而，由于缺乏成本效益高的护理点(POC)病毒载量分析，可以有效地接触到生活在农村、与世隔绝的患者，这一推广受到了显著限制。在发达国家，艾滋病毒-1病毒载量经常用于密切监测和评估患者对抗逆转录病毒疗法的反应，以确保药物依从性和疾病进展。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，遵循世卫组织的指南，但婴儿除外，因为婴儿需要进行病毒载量分析。这是因为HIV-1病毒载量分析昂贵(每次测试50-200美元)，依赖于仪器，而且技术复杂。然而，最近的研究表明，CD4细胞计数策略不能检测到早期的病毒学故障。这一失败导致耐药菌株在感染者体内积累，并降低了一线药物的疗效。因此，在护理点(POC)迫切需要一种快速、廉价和简单的病毒负载测试。在这里，微流控和光学成像技术将被用来创造一种新型的HIV-1病毒载量微芯片。据推测，开发的艾滋病毒-1病毒载量微芯片可以：(I)选择性地从全血中捕获艾滋病毒，(Ii)在临床截止范围内敏感(�10%误差范围)，廉价(1美元)，快速(15分钟内)，并自动处理指刺全血(100�L)，以帮助POC提供高质量的护理和治疗。这是一项技术驱动的提案，其动机是迫切而重要的临床需求。先前的工作已经证明，可以在芯片上从患者的全血中捕获和量化HIV-1。提出了以下不同但相互关联的具体目标：目标1：制造捕获艾滋病毒-1的一次性微芯片，目标2：通过将捕获艾滋病毒-1的微芯片与检测/量化系统相结合，开发一个便携系统，用于芯片上的艾滋病毒-1病毒载量，以及目标3：用200个艾滋病毒感染样本验证微芯片技术。这项拟议的技术广泛适用于具有合理描述的生物标记物的其他传染病，如流感、肝炎、疟疾和结核病。