Quantifying Heavy Metals in Interstitial Fluid for Remote Monitoring of Chronic Exposures

定量间质液体中的重金属用于慢性暴露的远程监测 摘要/摘要 慢性接触重金属(HM)与许多有害健康影响有关。HM 土壤和水的污染每年给美国和全球经济造成数万亿美元的损失 补救和医疗费用。在西方，HM污染与人类健康特别相关 美国包括铀(U)、镉(Cd)、钒(V)和砷(As)。毒性可以归因于 然而，个别HMS暴露在多种HMS中被怀疑具有添加或协同有害作用 对健康的影响。虽然一些研究已经描述了这些地区的地表水和沉积物含量 由于需要采集血液或尿液，测定有毒金属的生物负荷仍然具有挑战性 随着时间的推移，来自分散的农村人口的样本。 间质液(ISF)提取和分析的最新进展提示一种微创方法 可适用于纵向监测HM暴露和生物负荷 分散的社区。ISF可以用微针阵列(MA)收集，是丰富的 疾病和暴露生物标志物。 我们最终设想了一种可穿戴的微针贴片，可以邮寄给个人或分发给个人 通过社区中心。这些贴片会被戴上几个小时，然后回到一个 用于测量ISF HM水平的中心实验室。这个项目的中心假设是MA提取 ISF将实现HM暴露的微创量化，这将是一个高度稳定的指标 用于暴露评估。 本项目的目标是：1)建立用于HMS的电感耦合等离子体质谱分析的分析参数 MA提取的ISF，2)定量非接触者ISF的基础HM含量与血和尿 3)通过定义HM与HM之间的关系来刻画混合HM暴露模型 随着时间的推移，ISF、血液和尿液中的浓度。 这项工作直接与NIEHS的任务相一致，以发现环境如何影响 以促进更健康的生活“，通过开发微创、纵向的生物监测方法。 这个具有高度翻译性的项目促进了对HM生物分布的基本理解，同时 建立一个监测平台，提供可采取行动的数据，以加强预防保健和 补救措施。

Quantifying Heavy Metals in Interstitial Fluid for Remote Monitoring of Chronic Exposures SUMMARY/ABSTRACT Chronic exposure to heavy metals (HM) is associated with many detrimental health effects. HM contamination in soil and water costs trillions of dollars annually to the U.S. and global economies in remediation and health costs. HM contamination particularly relevant to human health in the Western U.S. includes uranium (U), cadmium (Cd), vanadium (V), and arsenic (As). Toxicity can be attributed to individual HMs, however exposure to multiple HMs is suspected to have additive or synergistic harmful health effects. While several studies have described the surface water and sediment content of these toxic metals, determining biological loads remains challenging due to the need to collect blood or urine samples from a dispersed rural population over time. Recent advances in interstitial fluid (ISF) extraction and analysis suggest a minimally-invasive method that can be adapted to monitor HM exposure and biological loads longitudinally in both localized and dispersed communities. ISF can be collected with microneedle arrays (MA) and is a rich source of disease and exposure biomarkers. We ultimately envision a wearable microneedle patch that could be mailed to individuals or distributed through community centers. These patches would be worn for a few hours and then returned to a central laboratory to measure ISF HM levels. The central hypothesis of this project is that MA extraction of ISF will enable minimally-invasive quantitation of HM exposure, which will be a highly stable metric for exposure assessment. The Aims of the current project are to 1) Establish analytical parameters for ICP-MS analysis of HMs in MA-extracted ISF, 2) Quantify the baseline HM content of ISF vs blood and urine in unexposed populations, and 3) Characterize a mixed HM exposure model by defining the relationship between HM concentrations in ISF, blood, and urine over time. This work directly aligns with the NIEHS Mission “to discover how the environment affects people in order to promote healthier lives” by developing minimally-invasive, longitudinal biomonitoring methods. This highly translational project advances the basic understanding of HM biodistribution while developing a monitoring platform that can provide actionable data to enhance preventive health and remediation efforts.