Multiplex Sensor Platform for Biological Monitoring

项目摘要 该研究项目直接支持NIOSH的研究目标，重点是“发展 衡量不良健康影响早期标志的方法”，特别侧重于 用于定量非侵入性生物监测的新技术。更具体地说，这个项目 直接针对NIOSH确定的农业工业部门的需求 农药暴露作为一个高度优先的研究。此外，该提案还特别针对 跨部门-风险评估战略目标#2的重点是， 制定和/或改进评估工人接触下列物质的具体方法和工具： 关键的职业因素和压力源。NIOSH的这些研究目标也完全 与国家研究理事会（NRC）的愿景一致，该理事会指出， 科学将在新的基于风险的毒性评估框架中发挥关键作用。在这 在这种情况下，生物监测是一个关键组成部分，定量地将内部剂量与 可衡量的效果。也有人认为，流行病学研究， 评估化学品暴露沿着生物效应将最有意义 解释，从而产生最大的影响。然而，在执行过程中的一个主要障碍是 流行病学研究中的定量生物监测缺乏快速，灵敏，现场 测量化学暴露/反应生物标志物的可部署的定量技术 使用微创生物流体（即唾液或血滴）。人类接触很少 单一的化学试剂，而是复杂的化学混合物。尤其如此 在农业中，多种农药组合和/或顺序施用， 作物由于职业暴露和生物系统的复杂性， 单一生物标志物的测量可能无法提供对 exposure.因此，该项目将进行开发，验证，并完善一个新的 能够定量与农药相关的多种生物标志物的多重传感器平台 暴露量（剂量），利用唾液、血液或尿液进行生物监测。此外，药代动力学 将利用评价来促进剂量测定的量化。因此，假设A 多重生物标记传感器可用于定量混合农药暴露（即， 全身剂量），通过测量生物体内的母体代谢物和胆碱酯酶（ChE） 样品该项目将特别侧重于开发一种多路传感器阵列， 已知容易通过唾液排泄的农药及其代谢物， 与血液浓度相关。这项研究的短期成果将包括 出版和介绍研究成果;而中期成果将侧重于 开发/测试具有最终结果的传感器平台（超出 目前的项目），使用传感器系统来测量并随后减少工人 接触农药。多路复用的开发、验证和随后的部署 传感器阵列平台作为测量混合农药职业暴露的定量工具 这与NIOSH研究实践（r2 P）倡议的目标完全一致。

Project Abstract This research project directly support NIOSH research objectives focused on the “development of methods for measuring early markers of adverse health effects”, with a specific focus on novel technologies for quantitative non-invasive biomonitoring. More specifically, this project directly targets the needs of the Agricultural Industry Sector where NIOSH has identified pesticide exposure as a high research priority. In addition, the proposal specifically addresses the Cross Sector- Exposure Assessment Strategic Goal #2 that is focused on, the development and/or improvement of specific methods and tools to assess worker exposures to critical occupational agents and stressors. These NIOSH research objectives are also fully consistent with the vision of the National Research Council (NRC) which noted that exposure science will play a critical role in a new risk-based toxicity assessment framework. In this context, biomonitoring is a key component that quantitatively associates an internal dose with a measurable effect. It has also been suggested that epidemiology studies which accurately assess chemical exposures along with biological effects will have the most meaningful interpretation and thus maximal impact. However, a major impediment in conducting quantitative biomonitoring within epidemiology studies is the lack of rapid, sensitive, field deployable, quantitative technologies that measure chemical exposure/response biomarkers using minimally invasive biological fluids (i.e. saliva or drop of blood). Human exposure is rarely to single chemical agents but rather to complex chemical mixtures. This is particularly true in agriculture where multiple pesticides are utilized in combination and/or sequential application to crops. Due to the complex nature of occupational exposures and biological systems, measurement of a single biomarker may not provide adequate quantitative assessment of exposure. Hence, this project will undertake development, validation, and refinement of a novel multiplex sensor platform capable of quantifying multiple biomarkers associated with pesticide exposures (dose), utilizing saliva, blood or urine for biomonitoring. In addition, pharmacokinetic evaluations will be exploited to facilitate quantifying dosimetry. Hence, it is hypothesized that a multiplex biomarker sensor can be used to quantify mixed pesticide exposures (i.e. systemic dose) by measuring parent metabolites and cholinesterase (ChE) in biological samples. This project will specifically focus on the development of a multiplex sensor array for those pesticides and their metabolites that are known to be readily excreted in saliva and correlate with blood concentrations. Short-term outcomes of this research will include publication and presentation of research results; whereas, intermediate outcomes will focus on development/testing of a sensor platform with an eventual end outcome (beyond scope of current project) of using the sensor system for measuring and subsequently reducing worker exposure to pesticides. The development, validation and subsequent deployment of a multiplex sensor array platform as a quantitative tool to measure mixed pesticide occupational exposures is fully consistent with the goals of the NIOSH Research to Practice (r2P) initiative.