Point of Care Detection of Respiratory Viruses

描述(由申请人提供)：呼吸道感染在全球范围内对健康和经济产生重大影响。目前用于诊断流感等呼吸道病毒感染的检测产品不足以及时诊断成功实施抗病毒治疗所需。不幸的是，还没有开发出一种能够在不到30分钟内直接在需要时准确诊断常见呼吸道病毒的测试产品。我们建议开发一种创新的设备和试剂，用于多种RNA病原体的分子诊断，这将为快速患者护理设定一个新的标准。这一名为“呼吸道病毒关注点检测”的申请寻求开发一种用于处理、检测和数字读出流感病毒A和B的交钥匙解决方案， 以及呼吸道合胞病毒(RSV)。对操作该设备的人员的培训要求很低。新的分子技术、简单的方案和经济实惠的多重测试能力驻留在一个廉价的设备中，将使许多严重感染性病原体能够在接近护理点的情况下进行诊断。实现这一目标的研究设计包括四个处理要素：1)可以立即完成的一步样品准备；2)在20分钟内对病毒RNA进行等温扩增；3)在几分钟内对甲型流感、乙型流感和呼吸道合胞病毒进行多重序列特异性检测，包括内置标准；以及4)电子结果的数字读出。这些步骤都是 发生在装有一次性试剂盒的4x6英寸小仪器内。实现这一改变游戏规则的技术的一个关键因素是开发了一种新型酶，它可以将RNA转化为DNA，并在几分钟内恒温放大它。这些属性使得不使用任何微流体、泵或阀的设备得以设计。大大简化了结构，大大降低了成本。这项新技术是低资源和低战场环境的理想选择，并具有作为场外设备的长期潜力。作为这一应用的一部分而开发的测试设备和试剂将在临床环境中与外部专家一起进行验证。在该项目的第三阶段，我们将申请FDA批准该仪器和试剂，并在美国和全球其他市场将该诊断设备商业化。 公共卫生相关性：这项应用的目标是开发一种简单但廉价的基于核酸的检测设备，可以在护理地点在不到30分钟的时间内诊断人类呼吸道病毒疾病。由于呼吸道疾病的治疗方案因病因的不同而有很大不同，这种新的临床诊断产品的开发、fda批准和最终商业化将对患者和他们的提供者产生深远的健康益处，使及时的诊断能够为抗病毒和 抗生素疗法。

DESCRIPTION (provided by applicant): Respiratory infections have a significant health and economic impact worldwide. Current test products for the diagnosis of respiratory viral infections such as influenza are inadequate for the timely diagnosis needed for successful implementation of antiviral treatment. Unfortunately a test product that can accurately diagnose common respiratory viruses with high confidence in less than 30 minutes directly at point of need has not yet been developed. We propose to develop an innovative device and reagents for the molecular diagnosis of multiple RNA pathogens that will set a new standard for rapid patient care. This application entitled "Point of Care Detection of Respiratory Viruses" seeks to develop a turnkey solution for the processing, detection, and digital readout of influenza viruses A and B, as well as respiratory syncytial virus (RSV) in 30 minutes. Training requirements for personnel operating the device are minimal. The combination of novel molecular technologies, simple protocol, and affordable multiplex testing capabilities residing in a single, inexpensive device wil enable near point of care diagnostics for a number of serious infectious agents. The research design for achieving this goal includes four processing elements: 1) A one step sample prep that can be completed in a minute, 2) Isothermal amplification of viral RNA in 20 minutes, 3) multiplex sequence specific detection of influenza A, influenza B and RSV including built in standards in a few minutes, and 4) a digital readout of results in electronic form. These steps all occur within a small 4 x 6 inch instrument containing a disposable reagent cartridge. A key factor enabling this game changing technology is the development of a novel enzyme that converts RNA to DNA and isothermally amplifies it in minutes. These attributes have allowed the design of a device that does not use any microfluidics, pumps or valves. The greatly simplified construction significantly reduces the cost. This new technology is ideal for to low resource and battlefield settings, and has long term potential as an over the counter device. The test device and reagents developed as part of this application will be validated in a clinical setting with outside experts. During Phase III of the project we will apply for FDA clearance of the instrument and reagents and commercialize the diagnostic device in the US and other markets around the globe. PUBLIC HEALTH RELEVANCE: The goal of this application is to develop a simple but inexpensive nucleic acid based test device that can diagnose human respiratory viral illness in less than 30 minutes at point of care. Because treatment regimens for respiratory disease differ widely depending on the causative agent, the development, FDA-approval and eventual commercialization of this new clinical diagnostic product would have profound health care benefits for patients and their providers by allowing timely diagnosis to inform both antiviral and antibiotic therapies.