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: 8233015
• 负责人: Richard Willson
• 金额: $ 61.75万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233015
• 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.

本项目的长期目标是开发一个超灵敏的抗原检测集成平台 诊断多种潜在的生物恐怖剂，基于微制造的新技术 回射器人们普遍认为，大多数恐怖袭击是隐蔽的，因此， 在第一个人患上重病并寻求医疗帮助之前，这一情况将是未知的。的可用性 一种能够同时检测几种病原体的仪器将大大提高我们对一种病原体的反应。 可能的生物恐怖袭击，因为有能力筛选病人提出非特异性的迹象， 症状（绝大多数）或基于综合征表现进行测试的可能性。 我们已经证明了微米级回射器的廉价制造和非常高的探测能力， 以及通过金纳米颗粒和磁性颗粒（用于与样品集成）的亮度调制 制备）。几百个40纳米的颗粒，或单个2.8微米的磁性颗粒， 珠，可以可靠地检测到一个大的后向反射器阵列的每个元件，与简单的光学潜在的 花费不到1000美元。目前正在对立克次体和诺沃克的人类临床样本进行检测 病毒和其他诺如病毒。使用磁性和/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，并通过使用共定位的 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。测试最初将集中在土拉热弗朗西斯菌， 隐孢子虫、裂谷热病毒、诺瓦克病毒和立克次氏体，并将协调 与诊断主题调查人员和WRCE主题专家就这些代理进行讨论。测试将 开始在体外使用减毒或灭活的试剂，并进展到使用动物和人类样本进行测试，以及 在德克萨斯大学医学分支的BSL-3和BSL-4设施中使用有毒物质。