Portable, rapid and user-friendly diagnostic system for chemical threat exposure

项目概述/摘要：在恐怖袭击或化学威胁剂意外释放后，数百名潜在受害者可能需要检测和治疗。对大量人群进行化学威胁剂暴露测试的迫切需要将超出临床和公共卫生基础设施的能力。许多临床和公共卫生设施缺乏快速诊断生物样品中指示特定暴露的生物标志物的能力。实验室反应网络中负责协调准备和反应的约25,000个哨点实验室需要诊断工具，以便能够进行准确的分散检测。医疗专业人员、军事部队和急救人员也迫切需要适用于检测化学威胁暴露并供紧急护理提供者用于指导医疗对策和治疗的快速和便携式诊断工具。该项目的目标是开发一种新的便携式诊断系统，能够快速检测生物样品（如尿液和血浆）中化学威胁剂的代谢物。正如最近在俄罗斯发生的恐怖袭击和警察干预所显示的那样，如果能够迅速确定具体的药剂，或者至少确定药剂的类别，接触未知化学物质的受害者可能会得到更成功的治疗。特别是，我们将通过开发化学威胁暴露的尿液测试来满足识别需要积极挽救生命治疗的患者的需求。该测试将测量指示特定暴露的生物标志物。所提出的测试条是基于结合诱导无标记荧光共振能量转移（FRET）检测。该技术采用化学威胁剂代谢物特有的适体分子信标作为识别元件，荧光量子点作为信号输出。该试纸条结合了高特异性和耐用的适体受体、纳米技术和免疫层析生物测定的优点。这项新研究将产生快速、自主、成本效益高、结果易于解释的比色条。拟议的比色试纸条将适用于医疗专业人员、军队和急救人员，以快速诊断和识别暴露于化学威胁剂的个人，以便及时治疗。在第一阶段，我们将展示用于检测神经毒气试剂主要代谢物（烷基甲基膦酸）的试纸条的可行性，在第二阶段，我们将开发试纸板，能够在患者生物样本的单次测量中分析指示特定暴露的多种生物标志物，以满足诊断系统在大因果关系期间的要求。项目说明：人类接触化学威胁剂可能导致疾病或功能障碍，以及大规模伤亡。这项拟议的研究旨在开发可穿戴诊断条，能够分析生物样本中指示特定暴露的生物标志物。

DESCRIPTION (provided by applicant): Project Summary/Abstract: Following a terrorist attack or accidental release of chemical threat agents, hundreds of potential victims may require testing and treatment. The critical need to test large numbers of people for exposure to chemical threat agents will overwhelm the capacity of the clinical and public health infrastructure. Many of the clinical and public health facilities lack the capabilities for rapid diagnosis of biomarkers indicative of specific exposures in biological samples. The ~25,000 sentinel laboratories in the Laboratory Response Network, which coordinate preparedness and response, need diagnostic tools to enable accurate decentralized testing. Rapid and portable diagnostic tools suitable for detection of chemical threat exposure and for use by emergency care providers in order to guide medical countermeasures and treatments are also in critical need by medical professionals, military forces, and first responders. The goal of the proposed project is to develop a new portable diagnostic system capable of rapidly detecting metabolites of chemical threat agents in biological samples such as urine and plasma. As shown in the recent terrorist attack and police intervention in Russia, victims of an exposure to an unknown chemical could have been treated more successfully if the specific agent, or at least the class of agent, could have been determined quickly. Specially, we will address the need for identifying patients that require aggressive life-saving therapy by developing a urine test for chemical threat exposure. The test will measure the biomarkers that are indicative of specific exposure. The proposed test strip is based on binding-induced label-free fluorescent resonance energy transfer (FRET) detection. The technology employs aptamer molecular beacons specific to metabolites of chemical threat agents, as recognition elements, and fluorescent quantum dots as signal output. The proposed test strip combines the advantages of highly specific and durable aptamer receptors, nanotechnology and immunochromatographic bioassays. This novel research will result in colorimetric strips with features of rapid, autonomous, cost-effective, and easily interpretable results. The proposed colorimetric test strips will be suitable for medical professionals, military forces and first responders to rapidly diagnose and identify individuals exposed to chemical threat agents for prompt treatment. In Phase I, we will demonstrate the feasibility of the test strip for detection of the major metabolites (alkyl methylphosphonic acid) of nerve gas reagents, and in Phase II, we will develop strip panels capable of assaying multiple biomarkers indicative of specific exposure in a single measurement of patient's biological sample to meet the requirement of a diagnostic system during large causality. Project Narrative: Human exposure to chemical threat agents may lead to disease or dysfunction, and mass casualty. This proposed research seeks to develop wearable diagnostic strips capable of assaying biomakers indicative of specific exposures in biological samples.