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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(申请人提供)：根据最近的估计，约有3300万艾滋病毒携带者，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，而且越来越容易获得，但护理标准要求定期监测患者的病毒载量，以个体化治疗，并控制艾滋病毒耐药株的出现和传播。目前，最常见的病毒载量评估方法是基于聚合酶链式反应的定量DNA分析或支链DNA分析，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情况下并不容易获得。因此，男性艾滋病毒患者不会接受建议的定期病毒载量检测。交流诊断公司(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，用于基于分子的血液中HIV-1检测和量化。该技术的核心是一种用于核酸检测的新型多功能恒温酶放大反应器，它利用膜捕获支架从复杂的样品中分离核酸，而无需事先纯化和洗脱，从而极大地简化了流动控制，并使分子诊断设备能够实现，这些设备仅比试纸略复杂，但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10个HIV拷贝(即少于100个拷贝/毫升血液)。目前正在开发的竞争技术使用昂贵而复杂的处理器，在世界许多地区可能负担不起。第一阶段将提供概念证明和针对B分支和C分支HIV-1亚型的目标。通过适当选择引物，在不对硬件进行任何修改的情况下，可以根据使用区域对该设备进行修改以检测其他分支。拟议的技术还将使艾滋病毒-1能够在高度传染性的血清转换前急性感染阶段及早发现，以便于及早治疗和最大限度地减少疾病的传播(这一点尤其重要，因为越来越强调“检测和治疗”和“治疗即预防”的概念)。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，因为持久的母体抗体使传统的检测变得不可能。这类婴儿通常在没有检测的情况下开始接受治疗，导致大多数婴儿过度治疗，以挽救少数感染者。我们的技术可以帮助防止不必要的暴露和费用。虽然发展中国家特别需要拟议的技术，但预计仪器(定量)和定性设备在发达国家也将有市场空间，特别是在远离主要医疗中心的地方；在基于病毒载量测量的“实时”决定可能有益的情况下，可能会提高效率、患者的便利性、坚持药物治疗，并使治疗决策更及时。我们的设备还可以用于家庭测试，以提供早期检测。