Nanomagnetic isolation and sensing for mobile HIV-1 self-testing

用于移动 HIV-1 自检的纳米磁隔离和传感

基本信息

批准号：
10224709
负责人：
David Aaron Issadore
金额：
$ 46.39万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-26 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224709
关键词：
Acids Acquired Immunodeficiency Syndrome Advanced Development Antigens Benchmarking Biological Markers Blood Blood Volume Car Phone Clinical Complex Coupled Data Analyses Detection Development Devices Diagnostic Disease Disease Progression Disease remission Drug resistance Early Diagnosis Elements Equipment Evaluation Fingers Future Geometry Goals Gold HIV HIV-1 Hand Home Human Label Laboratories Liquid substance Magnetism Methods Modeling Modification Monitor Nucleic Acids Oligonucleotides Outcome Patients Performance Plasma Preparation Procedures Reaction Recurrence Research Risk Sampling Specificity Specimen System T-Lymphocyte Technology Testing Time Variant Vesicle Viral Viral Load result Viremia Virus antibody detection antibody test antiretroviral therapy base clinically relevant commercialization cost design detection limit detection method drug efficacy graphene handheld mobile device individual patient innovation innovative technologies instrumentation manufacturability nanomagnetic nanopore nanoscale nanosensors noninvasive diagnosis novel nucleic acid detection point of care portability prototype self testing sensor tissue culture transmission process treatment strategy viral detection viral rebound

项目摘要

Project Summary Antiretroviral treatment (ART) requires close monitoring of HIV-1 plasma viremia to confirm viral suppression, and to identify viral rebound due to nonadherence or drug resistance to initiate timely treatment modification. Thus, frequent efficient monitoring for HIV in blood via methods that are accessible for home self-testing is a critical need. Current self-detection strategies only detect antibody, and existing virus detection methods require extensive equipment and expertise (RNA) and/or have limited sensitivity (antigen). We aim to fill this gap with the development of an inexpensive, automated, portable system that will detect new or recurrent plasma viremia with high specificity and sufficient sensitivity for self-monitoring in these contexts. The ultimate goal of this project is to develop a platform technology for low-cost (< $2/test) point-of-care nucleic acid diagnostics for use on crude human samples (plasma) to quantitate viral RNA with a detection limit < 10 virus / sample (equivalent to a clinically-relevant threshold of 1000 copy/ml on 10 ul finger prick blood). The method will be simple to perform and will not require complex amplification procedures such as PCR. The novelty of our approach is to combine two innovative technologies invented by our team - one for target separation and concentration suitable for any starting blood volume, and one for label-free nucleic acid detection without amplification – into an integrated device. The goal of our R66 is to design a laboratory-based integrated system to demonstrate quantitation of HIV viral load on tissue culture derived virus spiked into healthy plasma. The goals of our R33 are advanced development of our technology into a fully-automated handheld mobile-phone based device to be used by non-microfluidic experts, and evaluation using banked clinical samples through partnership with Penn's Center for AIDS Research.

项目摘要抗逆转录病毒治疗（ART）需要密切监测HIV-1血浆病毒血症以证实病毒抑制，并确定由于不遵守或耐药性而引起的病毒反弹及时的治疗修饰。那是通过方法经常有效地监测血液中艾滋病毒的艾滋病毒可以自我测试可以访问的是迫切需要。仅当前自我检测策略检测抗体，现有的病毒检测方法需要广泛的设备，并且专业知识（RNA）和/或具有有限的灵敏度（抗原）。我们的目的是用开发便宜，自动化的便携式系统，该系统将检测到新的或经常性的具有高特异性和足够灵敏度自我监测的血浆病毒率上下文。该项目的最终目标是为低成本开发平台技术（< $ 2/测试）用于在原油样品（等离子体）中使用的核酸诊断点定量具有检测极限<10病毒 /样品的病毒RNA（相当于临床上的 10 ul手指刺血上的1000副本/ml的阈值）。该方法将易于执行，并且不需要复杂的放大程序，例如PCR。我们方法的新颖性是结合我们团队发明的两种创新技术 - 一个用于目标分离和浓度适用于任何起始血容量，一种用于无标签的核酸检测无扩增的检测 - 进入集成设备。我们R66的目标是设计一个基于实验室的集成系统，以证明在组织上定量HIV病毒负荷培养的病毒刺激到健康的血浆中。我们R33的目标是提前的将我们的技术开发到完全自动的手持手机设备中由非微流体专家使用，并通过银行临床样本进行评估与宾夕法尼亚州艾滋病研究中心的合作伙伴关系。