Biosensor for real-time chemical monitoring

美国公民和海外军事人员面临的安全局势的变化大大增加了化学武器将在实地和国内对美国军队和美国平民使用的威胁。此外，每年有数十万美国人接触到大量的有机磷农药（OP）。这些情况表明迫切需要一种有效的，fieldable和廉价的方式来检测OP。检测仪器是任何保护范式的重要组成部分，因此，一个挑战是开发敏感和廉价的检测方法，用于各种OP代理。我们工作的目标是能够检测OP神经毒剂暴露的生物标志物，该生物标志物可以使用便携式自动化多分析物生物传感器容易且廉价地部署。我们的长期目标是开发一种灵敏的生物传感器来检测OP暴露的生物标志物，以提供信息来保护暴露于化学战剂或OP农药的风险人群。本研究的主要目的包括：1）设计并合成生物标记物试剂，用于检测包括塔崩、沙林、梭曼、VX、GF和塔崩在内的神经性毒剂，2）制备并检测神经性毒剂暴露生物标记物的抗体，3）获取暴露于神经性毒剂或其替代物的动物的生物样品，4）检测神经性毒剂暴露生物标记物的抗体。目的4）开发神经毒剂暴露的生物传感器和目的5）构建和测试最终的生物传感器。将与海军研究实验室合作，采用优化的试剂和现有技术，对一种耐用的便携式阵列生物传感器进行生物化学验证和开发。随着拟议工作的成功，我们将获得：1）用于鉴定与神经毒剂和农药OP暴露相关的OP-生物分子缀合物的新试剂和技术，2）用生物样品验证该技术的稳健性，3）开发一种基于阵列的方法，以选择性地检测OP; 4）利用从暴露于低剂量神经毒剂或神经毒剂类似物的动物中采集的生物样本，在现场制作和测试阵列生物传感器。最终的敏感性和选择性产品将用于OP暴露的生理液体的快速筛查形式。

DESCRIPTION (provided by applicant): Changes in the security situation facing citizens in the United States and military personnel abroad have greatly increased the threat that chemical weapons will be used against American forces and American civilians in the field as well as at home. In addition, hundreds of thousands of Americans are exposed to significant levels of pesticide organophosphates (OP) every year. These situations point to an urgent need for an efficient, fieldable and inexpensive way to detect OP. Detection instrumentation is an essential component of any protection paradigm, and thus a challenge is to develop sensitive and inexpensive detection methodology for various OP agents. The goal of our work is to be able to detect biomarkers of OP nerve agent exposure that can be readily and inexpensively deployed using a portable automated multianalyte biosensor. Our long-term goals are to develop a sensitive biosensor to detect biomarkers of OP exposure to provide information to protect populations at risk for exposure to chemical warfare agents or OP pesticides. The Aims for this research include: Aim 1) Design and synthesize biomarker reagents for a system to detect nerve agents including tabun, sarin, soman, VX, GF and tabun; Aim 2) Prepare and test antibodies to biomarkers of nerve agent exposure; Aim 3) Obtain biological samples from animals exposed to nerve agents or their surrogates; Aim 4) Develop the biosensor for nerve agent exposure and Aim 5) Build and test the final biosensor. Biochemical validation and development of a robust, portable Array Biosensor employing the optimized reagents and using currently available technology will be done in collaboration with the Naval Research Laboratory. With the success of the proposed work, we will obtain: 1) new reagents and technology for identifying OP-biomolecule conjugates of relevance to nerve agent and pesticide OP exposure, 2) verification of the robustness of the technology with biological samples, 3) development of an array-based methodology to selectively detect OP and 4) elaboration and testing of an Array Biosensor in the field with biological samples taken from animals exposed to low doses of nerve agents or nerve agent analogs. The final sensitive and selective product will be of use in a rapid screening format of physiological fluids for OP exposure.