Development of a selective biosensor for detecting organophosphate exposure

开发用于检测有机磷暴露的选择性生物传感器

• 批准号: 7226145
• 负责人: JON Owen NAGY
• 金额: $ 30.05万
• 依托单位: NAGY CONSULTING
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226145
• 关键词: antibody; biosensor device; human; peptides; pesticides; phosphopeptides; polymers; proteins; serum; university

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.

说明（由申请人提供）：该SBIR项目是响应开发化学品威胁暴露快速和便携式诊断工具的呼吁，适合紧急护理提供者使用，以指导医疗对策。本提案的总体目标是开发一种极其敏感和选择性的生物传感器装置，能够检测和区分从暴露于潜在有害水平的有机磷神经毒气的人员身上采集的人类血清样本中的蛋白质。这代表了生物标志物分析的一种新方法，因为暴露于每种不同的有机磷（OP）化学神经毒剂会产生独特的蛋白质“指纹”结构，可以识别，与其他毒剂区分开来，并进行量化。使用新型传感器聚合物薄膜技术，报告结构域将被定制为特定的蛋白质识别分子，以检测OP中毒的蛋白质。这将有可能开发出一种廉价、快速、准确的设备来分析暴露于OP化学剂，评估OP化学剂暴露的类型和程度，然后这些信息将用于指导必要的治疗干预。该项目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，其次证明在实际血清样品中可重复和准确地检测op修饰的蛋白质，第三，构建一个原型面包板设备，将指导商业生物传感器设备的设计。为了完成这些里程碑，我们与一个专门研究OP毒性蛋白的小组建立了合作关系。这些科学家将为膜偶联提供生物识别分子。熟悉生物偶联和薄膜制备的研究人员将构建传感器元件。然后将使用含有毒性蛋白质的人血清样本来测量薄膜反应。最后，光学和电气工程师将协助设计和组装原型演示装置。预计这种装置的最终用户将是可能遇到作战部队暴露于OP化学剂的情况的外勤人员和流动医疗单位，以及受到恐怖主义威胁的平民。公众可能接触到两类相关的有机磷（OP）化学剂是农药和神经毒气。通过意外过度暴露于农药或生物恐怖主义行为，这些制剂可以对人类造成致命伤害。实现拟议的生物传感器装置将使我们能够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。