Point of Care Device for Molecular Detection of HIV

用于 HIV 分子检测的护理点设备

基本信息

批准号：
8541659
负责人：
Haim H Bau
金额：
$ 30万
依托单位：
AC DIAGNOSTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-20 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8541659
关键词：
Acquired Immunodeficiency Syndrome Acute Adherence Antibodies Biological Assay Blood Blood specimen Buffers Cellular Phone Characteristics Clinical Collaborations Communicable Diseases Complex DNA Detection Developed Countries Developing Countries Development Devices Diagnosis Diagnostic Diagnostic Reagent Kits Diagnostic tests Disease Drug resistance Early Diagnosis Early treatment Encapsulated Equipment Evaluation Fluorescence Food Safety Fostering Funding Future Generations HIV HIV-1 Healthcare Home environment Immobilization Individual Infection Lead Life Marketing Maternal antibody Measures Mediating Medical center Membrane Microfluidics Modification Molecular Monitor Mothers Newborn Infant Nucleic Acids Partner in relationship Patient Monitoring Patients Pennsylvania Performance Pharmaceutical Preparations Pharmacotherapy Phase Plants Plastics Preparation Prevention Process RNA Reagent Research Research Infrastructure Resources Reverse Transcription Risk Sampling Sensitivity and Specificity Small Business Technology Transfer Research Southern Africa Specimen Staging System Technology Test Result Testing Time Transportation United States National Institutes of Health Universities Validation Viral Load result Virus Virus Diseases Whole Blood antiretroviral therapy assay development base cost design experience improved instrument laboratory facility man novel nucleic acid detection nucleic acid purification operation pathogen point of care prevent product development public health relevance research study resistant strain scaffold screening solid state standard of care success viral RNA viral detection

项目摘要

DESCRIPTION (provided by applicant): According to recent estimates ~33 million people are living with HIV, with 96% residing in the developing world. While antiretroviral therapy is effective and increasingly available, the standard of care requires periodic monitoring of patients' viral load to individualize treatment and to control the emergence and spread of drug- resistant strains of HIV. Currently, viral-load is most commonly assessed with quantitative PCR-based or branched chain DNA assays, which require expensive equipment, infrastructure, and skilled technicians, which are not readily available in resource-limited settings. As a result, man HIV patients are not subjected to the recommended periodic, viral load testing. AC Diagnostics (ACD), in collaboration with University of Pennsylvania (UPenn), will develop inexpensive, automated, fully-integrated, point of care devices for molecular-based detection and quantification of HIV-1 in blood. The core of the technology is a novel, multifunctional, isothermal enzymatic amplification reactor for nucleic acid detection that utilizes a membrane capture scaffold to isolate nucleic acids from complex samples without prior purification and without a need for elution, thereby greatly simplifying flow control and enabling molecular diagnostic devices that are just slightly more complicated than dipsticks and, yet, have nearly comparable performance of benchtop equipment. Our preliminary experiments indicate that the proposed device can detect as few as 10 HIV copies per sample (i.e., less than 100 copies/ml of blood) in less than 60 minutes. Competing technologies currently under development utilize expensive and complex processors and may be unaffordable in many regions of the world. Phase I will provide proof of concept and target clade B and clade C HIV-1 subtypes. By appropriate selection of primers and without any modifications in hardware, the device can be modified to detect other clades according to the region of use. The proposed technology will also enable early detection of HIV-1 during the highly contagious pre- seroconversion acute-stage of infection to facilitate early treatment and minimize the spread of the disease (which is particularly important with increasing emphasize on "test-and-treat" and "treatment-as-prevention" concepts). Yet another important application is the diagnosis of infection in babies born to HIV-infected mothers since persistent maternal antibody makes traditional testing impossible. Such babies are typically started on therapy without testing, resulting in overtreatment of the majority to save the few infected. Our technology can help prevent unneeded exposure and expense. Although the proposed technology is particularly needed in developing countries, it is anticipated that both the instrumented (quantitative) and qualitative devices will also have market niche in the developed world, especially in places located far from major medical centers; in settings when "real-time" decisions based on viral load measures may be beneficial, and would likely improve efficiency, patients' convenience, adherence to drug therapy, and enable more timely, treatment decisions. Our devices can also be used for home testing to provide early detection.

描述（由申请人提供）：根据最近的估计，约有 3300 万人感染艾滋病毒，其中 96% 居住在发展中国家。虽然抗逆转录病毒疗法是有效的并且越来越容易获得，但护理标准要求定期监测患者的病毒载量，以进行个体化治疗并控制艾滋病毒耐药株的出现和传播。目前，病毒载量最常通过基于定量 PCR 或支链 DNA 测定进行评估，这需要昂贵的设备、基础设施和熟练的技术人员，而这些在资源有限的环境中并不容易获得。因此，男性艾滋病毒患者没有接受建议的定期病毒载量检测。 AC Diagnostics (ACD) 与宾夕法尼亚大学 (UPenn) 合作，将开发廉价、自动化、完全集成的护理点设备，用于血液中 HIV-1 的分子检测和定量。该技术的核心是一种用于核酸检测的新型多功能等温酶扩增反应器，它利用膜捕获支架从复杂样品中分离核酸，无需事先纯化，无需洗脱，从而大大简化了流量控制，使分子生物学成为可能。诊断设备仅比量油尺稍微复杂一些，但其性能几乎与台式设备相当。我们的初步实验表明，所提出的设备可以在不到 60 分钟的时间内检测到每个样本中少至 10 个 HIV 拷贝（即每毫升血液少于 100 个拷贝）。目前正在开发的竞争技术使用昂贵且复杂的处理器，并且在世界许多地区可能难以承受。第一阶段将提供概念验证并针对 B 型和 C 型 HIV-1 亚型。通过适当选择引物并且无需对硬件进行任何修改，可以修改该设备以根据使用区域检测其他进化枝。所提出的技术还将能够在感染的高度传染性血清转换前急性阶段早期检测出 HIV-1，以促进早期治疗并最大限度地减少疾病的传播（这对于日益强调“检测和治疗”尤为重要） ”和“治疗即预防”概念）。另一个重要的应用是诊断感染艾滋病毒的母亲所生婴儿的感染情况，因为持久的母体抗体使传统检测变得不可能。这些婴儿通常在没有进行检测的情况下就开始接受治疗，导致对大多数婴儿进行过度治疗以拯救少数感染者。我们的技术可以帮助防止不必要的暴露和费用。尽管发展中国家特别需要所提出的技术，但预计仪器化（定量）和定性设备在发达国家也将具有市场利基，特别是在远离主要医疗中心的地方；当基于病毒载量测量的“实时”决策可能是有益的，并且可能会提高效率、患者的便利性、药物治疗的依从性并实现更及时的治疗决策时。我们的设备还可用于家庭测试，以提供早期检测。