Development of Near Real-Time, Multiplexed Diagnostics for Viral Hemorrhagic Feve

病毒性出血热近实时多重诊断的开发

• 批准号: 8511558
• 负责人: John H Connor
• 金额: $ 83.62万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511558
• 关键词: Africa; Animal Model; Antigens; Biological Assay; Biosensor; Boston; Categories; Centers for Disease Control and Prevention (U.S.); Clinical; Collaborations; Communicable Diseases; Communities; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Discipline; Disease; Disease Outbreaks; Dose; Ebola Hemorrhagic Fever; Endemic Diseases; Engineering; Epidemic; Etiology; Generations; Goals; Image; Individual; Infection; Infectious Agent; Label; Light; Medical; Methods; Microfluidics; Miniaturization; Nucleic Acid Amplification Tests; Particle Size; Pathogen detection; Patients; Positioning Attribute; Preparation; Process; RNA Viruses; Reporting; Research Personnel; Resources; Sampling; Satellite Viruses; Serum; Small RNA; Specificity; Symptoms; System; Techniques; Technology; Telecommunications; Testing; Time; Universities; Viral; Viral Hemorrhagic Fevers; Virion; Virus; Work; base; biodefense; biothreat; clinically relevant; design; detector; experience; flu; hemorrhagic fever virus; large scale production; multidisciplinary; nanopattern; next generation; pathogen; photonics; point of care; point-of-care diagnostics; prototype; rapid detection; research clinical testing; response; sensor; success; technology development; tool; virus development

DESCRIPTION (provided by applicant): Hemorrhagic fever viruses such as Ebola, Marburg and Lassa are responsible for current endemic diseases in Africa and are classified as Category A biothreats by the CDC because of the high fatality that can be associated with these diseases and their low infectious dose. Because of the concern of the release of weaponized Ebola, Marburg or Lassa, simple and effective detection and diagnostics are essential. While there are several existing assays for diagnosing infection with these viruses, they involve significant biosafety considerations, as the assays are not closed system sample-to-answer systems. This reduces the ability of these assays to be used in routine clinical testing and point-of-care settings. We propose to investigate the potential for nanophotonics technologies as rapid and multiplexed detection systems to diagnose infection with hemorrhagic fever viruses. We have chosen two technologies, pioneered by Boston University researchers, photonic nanohole arrays and interferometric reflectance imaging as our primary detection platforms. We will develop both technologies initially in a competitive manner. Both technologies have shown promise in their ability to show multiplexed detection of different antigens and pathogens. Based on the specific criteria of sensitivity (<104 PFu/ml) and specificity, we will select the most promising technology (or a complementary combination) for development of an integrated sample-to-answer prototype detector. The prototype detector will be an integrated system that will incorporate microfluidics, a multiplexed detector with the capacity to distinguish Ebola, Marburg, and Lassa infection. The system will be designed to initiate diagnosis from serum, and provide a closed-system sample-to-answer diagnostic that is rapid and easy to use. This system will serve as a proof of concept system to drive the development of photonic technologies as portable diagnostics. Photonics systems have the advantage of being rapid, label-free systems with an established record of miniaturization and inexpensive manufacture. Thus, these technologies provide an important avenue of exploration for new portable devices. To accomplish these goals we have assembled a multidisciplinary team with complementary expertise. To facilitate the development of the detector technology itself, the team includes experts in microfluidics, nanohole array development, and interferometric detection. To drive the testing and capture probe development technology, the team includes experts in pseudotype development to allow BSL2-testing and animal model experts familiar with all of the VHF viruses that will be analyzed. Prototyping will be facilitated through collaboration with Becton Dickinson, a company with significant experience in the development of virus diagnostics. Based on the strength of the team that we have assembled, we believe that we are well positioned to properly investigate the potential for nanophotonics systems as low power diagnostics that are simple and have a straightforward path to miniaturization and application in both clinical and point-of-care in resource limited settings.

描述（由申请人提供）：诸如埃博拉病毒，马尔堡和拉萨等出血热病毒负责非洲当前的地方性疾病，并将其归类为CDC类别的A类生物治疗，因为可能与这些疾病及其低死亡有关传染剂量。由于关注释放武器化的埃博拉病毒，马尔堡或拉萨，因此简单有效的检测和诊断至关重要。尽管有几种现有的测定方法可以诊断这些病毒感染，但它们涉及大量的生物安全考虑因素，因为这些测定不是封闭的系统样品对撤离系统。这降低了这些测定法在常规临床测试和护理点环境中使用的能力。我们建议研究纳米光子技术作为快速和多路复用检测系统的潜力，以诊断出患有出血热病毒的感染。我们选择了两种技术，由波士顿大学研究人员，光子纳米荷尔阵列和干涉反射成像作为我们的主要检测平台。我们最初将以竞争方式开发这两种技术。这两种技术都表现出他们显示出对不同抗原和病原体多路复用检测的能力的希望。基于灵敏度的特定标准（<104 PFU/mL）和特异性，我们将选择最有前途的技术（或互补组合）来开发集成的样品到撤回的原型检测器。原型探测器将是一个集成系统，该系统将结合微流体，该系统是一个多重检测器，具有区分埃博拉病毒，马堡和LASSA感染的能力。该系统将旨在从血清启动诊断，并提供快速且易于使用的封闭系统样本对诊断的诊断。该系统将作为概念系统的证明，以推动光子技术作为便携式诊断。光子系统具有快速，无标签的系统的优势，并具有既定的微型化和廉价制造的记录。因此，这些技术为新的便携式设备提供了重要的探索途径。为了实现这些目标，我们已经组建了一个具有互补专业知识的多学科团队。为了促进探测器技术本身的开发，该团队包括微流体，纳米 - 纳米阵列开发和干涉测量检测的专家。为了推动测试和捕获探针开发技术，该团队包括假型开发专家，以允许BSL2测试和动物模型专家熟悉所有将要分析的VHF病毒。原型制作将通过与Becton Dickinson的合作来促进，该公司在病毒诊断的发展方面具有丰富的经验。基于我们组装的团队的实力，我们认为，我们可以很好地调查纳米光子系统系统的潜力，这是简单的低功率诊断，并且在临床和点上具有简单的小型化和应用道路 - 资源有限设置中的护理。