Development of a selective biosensor for detecting organophosphate exposure

描述（由申请人提供）：该SBIR项目是为了响应开发快速和便携式化学威胁暴露诊断工具的呼吁，适用于紧急护理提供者，以指导医疗对策。该提案的广泛目标是开发一种极其灵敏和选择性的生物传感器装置，该装置能够检测和区分从暴露于潜在有害水平的有机磷酸酯基神经毒气的人员中采集的人血清样品中的蛋白质。这代表了生物标志物分析中的一种新方法，因为暴露于每种不同的有机磷酸盐（OP）化学神经毒剂会导致不同的蛋白质“指纹”结构，该结构可以被识别，与其他试剂区分开来，并进行量化。使用新的传感器薄膜聚合物技术，报告域将定制特定的蛋白质识别分子，检测OP中毒的蛋白质。这将使得有可能开发一种廉价、快速和准确的设备来分析OP化学制剂的暴露，评估OP制剂暴露的类型和程度，然后将这些信息用于指导必要的治疗干预。该计划的主要里程碑是首先证明薄膜传感器元件的灵敏度和可靠性，其次证明实际血清样品中OP修饰蛋白的可重复和准确检测，第三，构建一个原型试验板设备，将指导商业生物传感器设备的设计。为了实现这些里程碑，与一个专门研究OP蛋白质的小组建立了合作关系。这些科学家将为膜结合提供生物识别分子。熟悉生物共轭和薄膜制备的研究人员将构建传感器元件。然后使用含有纯化蛋白的人血清样品测量胶片响应。最后，将利用光学和电气工程师协助设计和组装原型演示设备。这种装置的最终用户预计是可能遇到作战部队接触OP化学剂的情况的外勤人员和移动的医疗单位以及受到恐怖主义威胁的平民。潜在的公众暴露于两类相关的有机磷（OP）化学制剂是农药和神经毒气。通过意外过量接触杀虫剂或生物恐怖主义行为，这些物质可能对人类造成致命伤害。所提出的生物传感器装置的实现将允许前所未有地快速评估OP暴露的类型和程度，并指导医务人员采取适当的治疗方式。

DESCRIPTION (provided by applicant): This SBIR project is in response to the call for the development of rapid and portable diagnostic tools for chemical threat exposure, suitable for use by emergency care providers in order to guide medical countermeasures. The broad objective of this proposal is to develop an extremely sensitive and selective biosensor device capable of detecting and discriminating proteins in human serum samples taken from personnel that have been exposed to potentially harmful levels of organophosphate-based nerve gas. This represents a novel approach in biomarker analysis because exposure to each different organophosphate (OP) chemical nerve agent results in a distinct protein "fingerprint" structure that can be identified, distinguished from other agents, and quantified. Using novel sensor thin polymer film technology, reporter domains will be customized with specific protein-recognition molecules that detect the OP poisoned proteins. This will make it possible to develop an inexpensive, yet highly rapid, and accurate device to analyze exposure to OP chemical agents, assess the type and extent of OP agent exposure and then this information will be used to guide the therapeutic intervention necessary. The major milestones in this program are first to show proof-of-principal for the sensitivity and reliability of the film sensor element, second to demonstrate reproducible and accurate detection of OP-modified proteins in actual serum samples, and third, construct a prototype breadboard device that will guide the design of the commercial biosensor device. To accomplish these milestones, a collaboration has been established with a group specializing in OP toxified proteins. These scientists will provide the biorecognition molecules for film conjugation. Researchers familiar with bioconjugation and film preparation will construct the sensor elements. Samples of human serum containing toxified proteins will be then used to measure the film response. Finally, optical and electrical engineers will be utilized to assist in designing and assembling the prototype demonstration device. The end user of such a device is anticipated to be the field personnel and mobile medical units likely to encounter situations where combat troops have been exposed to OP chemical agents as well as civilians placed under terrorist threat. Potential public exposure to two classes of related organophosphate (OP) chemical agents are pesticides and nerve gases. Through either accidental over-exposure to pesticides or acts of bioterrorism, these agents can fatally harm humans. Realization of the proposed biosensor device will allow, as never before, rapid assessment of type and degree of OP exposure, and direct medical personnel to appropriate treatment modalities.