Multiplex Sensor Platform for Biological Monitoring

项目摘要 本研究项目直接支持NIOSH重点研究目标的《发展 关于测量不良健康影响的早期标志物的方法“，特别侧重于 定量非侵入性生物监测新技术。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 将农药暴露作为一个高度优先的研究重点。此外，该提案还具体涉及 重点关注的跨部门风险暴露评估战略目标2 制定和/或改进具体的方法和工具，以评估工人暴露于 关键职业诱因和压力源。这些NIOSH的研究目标也完全是 与国家研究委员会(NRC)的愿景一致，NRC注意到 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 背景，生物监测是定量地将内部剂量与 可衡量的影响。也有人建议，流行病学研究准确地 评估化学暴露以及生物影响将是最有意义的 解释，从而产生最大的影响。然而，传导的一个主要障碍是 流行病学研究中的定量生物监测缺乏快速、灵敏、现场 可部署的量化技术，用于测量化学暴露/反应生物标志物 使用微创的生物液体(如唾液或一滴血)。人类很少接触到 适用于单一化学试剂，而不适用于复杂的化学混合物。这一点在 多种农药组合使用和/或顺序使用的农业 庄稼。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不能提供足够的定量评估 曝光。因此，这个项目将承担一部小说的开发、验证和提炼 可定量检测与农药相关的多个生物标志物的多重传感器平台 暴露(剂量)，利用唾液、血液或尿液进行生物监测。此外，药代动力学 将利用评估来促进剂量测定的量化。因此，假设一个 多重生物标志物传感器可用于量化混合农药暴露(即 全身剂量)通过测量母体代谢物和生物中的胆碱酯酶(ChE) 样本。该项目将专门致力于开发多路传感器阵列 那些已知很容易从唾液中排泄出来的杀虫剂及其代谢物 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 当前项目)使用传感器系统测量并随后减少工人 接触杀虫剂。综合设施的开发、验证和后续部署 传感器阵列平台作为混合农药职业暴露测量的定量工具 与NIOSH研究实践(R2P)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.