Novel disposable microchips for HIV-1 viral load

描述（由申请人提供）：为了降低艾滋病毒/艾滋病感染者的发病率并提高其生活质量，世界卫生组织（世卫组织）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，由于缺乏能够有效覆盖生活在农村、隔离环境中的患者的具有成本效益的护理点（POC）病毒载量检测，这种扩展受到了显着限制。在发达国家，HIV-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对疾病进展进行分期。相比之下，发展中国家正在使用CD 4+细胞计数和临床症状来指导遵循世卫组织指南的抗逆转录病毒疗法，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病毒载量检测昂贵（每次检测50 -200美元），依赖于仪器，技术复杂。然而，最近的研究表明，CD 4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感染个体中积累，并降低一线药物的疗效。因此，在护理点（POC）迫切需要快速，廉价和简单的病毒载量测试。在这里，微流体和光学成像技术将用于创建一种新型的HIV-1病毒载量微芯片。据推测，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）在临床截止值内敏感（误差范围为10%），便宜（<1美元），快速（15分钟内），并自动处理手指穿刺全血（100 L），以帮助POC的优质护理和治疗。这是一项技术驱动的提案，其动机是迫切的重大临床需求。先前的工作已经证明了可以从患者全血芯片上捕获和定量HIV-1的概念。提出了以下不同但相互关联的具体目标：目标1：构建一次性微芯片以捕获HIV-1，目标2：通过将HIV-1捕获微芯片与检测/定量系统集成，开发用于芯片上HIV-1病毒载量的便携式系统，以及目标3：用200个HIV感染样本验证微芯片技术。该技术可广泛应用于具有合理描述的生物标志物的其他传染病，如流感、肝炎、疟疾和结核病。 公共卫生相关性：为了降低艾滋病毒/艾滋病患者的发病率并提高其生活质量，发展中国家正在迅速扩大获得抗逆转录病毒治疗的机会。然而，这种扩展受到缺乏具有成本效益的病毒载量监测工具的严重限制。为了帮助艾滋病毒/艾滋病患者的高质量护理和治疗，我们提出了一种新型的艾滋病毒载量微芯片，它：（i）能够选择性地从全血中捕获艾滋病毒，（ii）在临床截止值（约10%）误差范围内敏感，便宜（<1美元）， 快速（15分钟内），并自动处理手指穿刺全血（100 L）。

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).