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（由适用提供）：为了减少艾滋病毒/艾滋病患者的发病率和改善生活质量，世界卫生组织（WHO）正在迅速扩大发展中国家接受抗逆转录病毒疗法（ART）的机会。但是，由于缺乏具有成本效益的护理点（POC）病毒负荷测定法，CN有效地吸引了生活在农村，孤立的环境中的患者，因此显着限制了这种扩张。在发达国家，HIV-1病毒负荷经常用于密切监测和评估患者对ART的反应，以确保药物依从性和疾病进展。相比之下，发展中国家使用CD4+细胞计数和临床症状来指导ART遵循WHO指南，而婴儿需要进行病毒载荷评估。这是因为HIV-1病毒负荷评估价格昂贵（每次测试50-200美元），依赖仪器和技术复杂。然而，最近的研究表明，CD4细胞计数策略无法检测到早期的病毒学衰竭。这种失败导致感染个体中抗药性菌株的积累，并降低一线药物的有效性。在护理点（POC）迫切需要快速，廉价且简单的病毒负荷测试。在这里，将使用微流体和光学成像技术来创建一种新型的HIV-1病毒载荷微芯片。假设开发的HIV-1病毒载荷微芯片可以：（i）在临床截止中有选择地捕获HIV，（ii）在临床截止期内（误差范围为10％），廉价（<$ 1），快速（15分钟内），自动化以自动化手指 - 纯种血液（100°L）以帮助质量护理和治疗。这是由紧急临床需求促进的技术驱动的建议。先前的工作表明，概念概念可以从患者全血片中捕获并量化HIV-1。提出了以下独特但相互关联的特定目的：目标1：构建一次性微芯片以捕获HIV-1，AIM 2：通过将HIV-1捕获HIV-1用检测/量化系统整合HIV-1来开发用于芯片HIV-1病毒载荷的便携式系统，AIM 3：以3：与200 HIV验证的Microchip技术与200 HIV感染的样品验证。这项提出的技术广泛适用于其他具有相当描述性生物标志物的传染病，例如影响力，肝炎，疟疾和结核病。