Biosensor for real-time chemical monitoring

描述(申请人提供)：美国公民和海外军事人员面临的安全局势的变化极大地增加了化学武器将在外地和国内对美国军队和美国平民使用的威胁。此外，每年数十万美国人接触到大量的农药有机磷(OP)。这些情况表明，迫切需要一种有效、可现场和廉价的方法来检测OP。检测仪器是任何保护范例的重要组成部分，因此开发针对各种OP试剂的灵敏且廉价的检测方法是一项挑战。我们工作的目标是能够检测暴露于OP神经毒剂的生物标记物，这些标记物可以使用便携式自动多分析生物传感器轻松且廉价地部署。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杀虫剂的危险人群。本研究的目的包括：1)设计和合成用于检测神经毒剂包括tabun、沙林、梭曼、VX、GF和tabun的生物标志物试剂；目的2)制备和测试神经毒剂暴露生物标志物的抗体；目的3)从接触神经毒剂或其替代物的动物身上获取生物样本；目的4)研制神经毒剂暴露生物传感器；目的5)建立并测试最终的生物传感器。将与海军研究实验室合作，利用优化的试剂和目前可用的技术，进行生化验证和开发坚固的便携式阵列生物传感器。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-生物分子结合物的新试剂和技术，2)用生物样本验证该技术的稳健性，3)基于阵列的方法的发展，以选择性地检测OP，以及4)现场制作和测试阵列生物传感器，使用从接触低剂量神经毒剂或神经毒剂类似物的动物的生物样本。最终的敏感和选择性产品将用于OP暴露的生理液体的快速筛选格式。

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.