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3,300万人患有艾滋病毒，其中96％的人居住在发展中国家。虽然抗逆转录病毒疗法有效并且越来越可用，但护理标准需要定期监测患者的病毒负荷以个性化治疗并控制HIV抗药性菌株的出现和传播。目前，最常使用基于定量的PCR或分支链DNA分析来评估病毒负载，这些链DNA分析需要昂贵的设备，基础设施和熟练的技术人员，这些技术人员在资源有限的设置中不容易获得。结果，男性艾滋病毒患者未进行建议的周期性病毒负荷测试。 AC诊断（ACD）与宾夕法尼亚大学（UPENN）合作，将开发廉价，自动化，完全集成的护理设备，用于基于分子的血液检测和量化HIV-1的血液中的HIV-1。该技术的核心是一种新颖的，多功能的等温酶扩增反应器，用于检测核酸检测，它利用膜捕获脚手架将脚手架与无需洗脱的复杂样品分离出核酸，从而极大地简化了流动控制和更为多样性的分子诊断设备，并且可以使分子诊断设备变得更加复杂。设备。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品（即少于100份/ml的血液）的10份HIV拷贝。目前正在开发的竞争技术利用了昂贵且复杂的处理器，并且在世界许多地区可能无法负担。第一阶段将提供概念证明，目标进化枝B和进化枝C HIV-1亚型。通过适当选择底漆，没有任何硬件修改，可以修改设备以根据使用区域检测其他进化枝。所提出的技术还将在高度传染性的血清转化前感染急性阶段对HIV-1进行早期检测，以促进早期治疗并最大程度地减少该疾病的传播（这尤其重要地强调了“测试和治疗”和“治疗方法预先预期”的概念）。另一个重要的应用是艾滋病毒感染的母亲出生的婴儿的感染诊断，因为持续的母体抗体使传统的测试变得不可能。这些婴儿通常在没有测试的情况下开始接受治疗，导致大多数人过度治疗以节省少数被感染。我们的技术可以帮助防止不必要的曝光和费用。尽管在发展中国家特别需要该提议的技术，但预计仪器（定量）和定性设备都将在发达国家中具有市场利基市场，尤其是在远离主要医疗中心的地方；在基于病毒负荷测量的“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，对药物治疗的依从性以及更及时的治疗决策。我们的设备也可以用于家庭测试以提供早期检测。