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抗挑选的超敏化平台 基于微生物的新技术，诊断多种潜在的生物异常剂 复古反射器。广泛认为，大多数恐怖袭击都是秘密的，因此是感染者 在第一人民急性病并寻求医疗帮助之前，将是未知的。可用性 能够同时检测几个代理的仪器将大大增强我们对 由于能够筛查患者出现非特异性体征和 症状（绝大多数）或基于综合征表现的可能性。 我们已经证明了廉价的制造和微米级后流电流的高可检测性， 金纳米颗粒和磁性颗粒的亮度调节（用于与样品集成 制备）以分析物响应方式。几百40 nm颗粒或一个2.8 urn磁性 珠子，可以在大逆转录器阵列的每个元素上可靠地检测到，并具有简单的光学元件 成本不到$ 1000。 Rickettsiae和人类的临床样本正在进行测试 病毒和其他诺病毒。使用磁性和/或流体剪切去除可以实现很高的特异性 非特异性结合的颗粒，通过严格控制反射器亮度均匀性，并通过使用 参考反射器。 我们建议开发基于微流体的便携式，用户友好，准确和超敏感的设备 能够并联检测多种病原体。测试最初将集中于弗朗西斯氏菌， 隐孢子虫，裂谷谷发烧病毒，诺沃克病毒和立克人士，并将协调 与诊断主题研究者和WRCE主题专家有关这些代理商。测试将 从衰减或杀死的剂中开始体外，并进行用动物和人类标本进行测试，然后 在德克萨斯大学医学分公司的BSL-3和BSL-4设施中，有强大的代理商。