Towards the Development of a Syndrome-specific Diagnostic Tool

开发针对特定症状的诊断工具

• 批准号: 8377050
• 负责人: Richard Willson
• 金额: $ 61.1万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8377050
• 关键词: Animals; Antigens; Attenuated; Binding; Biological Assay; Blood; Categories; Clinical; Consult; Coupled; Cryptosporidium parvum; Detection; Development; Devices; Diagnosis; Diagnostic; Elements; Excision; Feces; Francisella tularensis; Goals; Gold; Human; In Vitro; Infectious Agent; Liquid substance; Magnetism; Medical; Microfluidics; National Institute of Allergy and Infectious Disease; Norovirus; Norwalk virus; Optics; Patients; Persons; Preparation; Research Personnel; Rickettsia; Rickettsia rickettsii; Rift Valley fever virus; Sampling; Signs and Symptoms; Specificity; Specimen; Syndrome; Technology; Testing; Texas; Universities; Virulent; Work; base; biodefense; biosafety level 4 facility; cost; instrument; killings; magnetic beads; member; nanoparticle; new technology; particle; pathogen; point of care; portability; response; tool; user-friendly

The long term goal of this project is the development of an ultrasensitive integrated platform for the antigendetection diagnosis of multiple potential bioterror agents, based on the novel technology of microfabricated retro-reflectors. It is widely accepted that most terrorist attacks are covert, and therefore the infectious agent will be unknown until the first person becomes acutely ill and seeks medical help. The availability of an instrument capable of detecting several agents simultaneously would greatly enhance our response to a possible bioterror attack because of the ability to screen patients presenting with non-specific signs and symptoms (the vast majority) or the possibility of testing based on syndromic presentation. We have demonstrated the inexpensive fabrication and very high detectability of micron-scale retroreflectors, and brightness modulation by gold nanoparticles and magnetic particles (for integration with sample preparation) in an analyte-responsive manner. A few hundred 40 nm particles, or a single 2.8 urn magnetic bead, can be reliably detected on each element of a large retroreflector array, with simple optics potentially costing less than $1000. Testing is underway with rickettsiae and with human clinical samples for Norwalk virus and other noroviruses. Very high specificity can be achieved using magnetic and/or fluid-shear removal of non-specifically bound particles, by tight control of reflector brightness uniformity, and by the use of colocated reference reflectors. We propose development of a microfluidics-based portable, user-friendly, accurate and ultrasensitive device capable of detecting multiple pathogens in parallel. Testing will initially focus on Francisella tularensis, Cryptosporidium parvum, Rift Valley fever virus, Norwalk virus, and Rickettsia rickettsii, and will coordinate with the Diagnostics Theme investigators and WRCE subject matter experts on these agents. Testing will begin in vitro with attenuated or killed agent, and progress to testing with animal and human specimens, and with virulent agents in the University of Texas Medical Branch's BSL-3 and BSL-4 facilities.

该项目的长期目标是开发用于抗原检测的超灵敏集成平台 基于微制造新技术的多种潜在生物恐怖分子的诊断 后向反射器。人们普遍认为，大多数恐怖袭击都是秘密的，因此传染源 直到第一个人病重并寻求医疗帮助之前，一切都是未知的。的可用性 能够同时检测多种试剂的仪器将大大增强我们对 可能的生物恐怖袭击，因为能够筛查出现非特异性体征的患者，并且 症状（绝大多数）或根据症状表现进行测试的可能性。 我们已经证明了微米级后向反射器的廉价制造和非常高的可检测性， 以及金纳米颗粒和磁性颗粒的亮度调节（用于与样品集成） 制备）以分析物响应的方式。数百个 40 nm 粒子，或单个 2.8 um 磁性粒子 珠子，可以通过简单的光学器件在大型后向反射器阵列的每个元件上进行可靠检测 成本不到 1000 美元。正在对诺沃克立克次体和人体临床样本进行测试 病毒和其他诺如病毒。使用磁力和/或流体剪切去除可以实现非常高的特异性 通过严格控制反射器亮度均匀性以及使用同位 参考反射器。 我们建议开发一种基于微流体的便携式、用户友好、准确和超灵敏的设备 能够并行检测多种病原体。测试最初将集中于土拉弗朗西斯菌， 小隐孢子虫、裂谷热病毒、诺瓦克病毒和立克次氏体，并将协调 与诊断主题调查员和 WRCE 主题专家一起研究这些代理。测试将 从减毒或灭活剂开始进行体外测试，然后进行动物和人体样本测试，以及 德克萨斯大学医学分部的 BSL-3 和 BSL-4 设施中含有剧毒制剂。