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

定量组织液中的重金属以远程监测慢性暴露

• 批准号: 10268165
• 负责人: Justin Thomas Baca
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-23 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268165
• 关键词: Affect; Animal Model; Animal Testing; Animals; Area; Arsenic; Biodistribution; Biological; Biological Markers; Biological Monitoring; Biopsy; Blood; Blood capillaries; Cadmium; Cardiovascular Diseases; Characteristics; Chronic; Code; Collection; Communities; Data; Disease; Dose; Environment; Exposure to; Extracellular Fluid; Future; General Population; Grant; Health; Health Care Costs; Heavy Metals; Hour; Human; Human Volunteers; In Vitro; Individual; Inductively Coupled Plasma Mass Spectrometry; Ingestion; Intercellular Fluid; Kidney Diseases; Laboratories; Malignant Neoplasms; Measurement; Measures; Metal exposure; Metals; Methodology; Methods; Microdialysis; Mining; Mission; Modeling; Monitor; National Institute of Environmental Health Sciences; Navajo; Occupations; Outcome; Population; Populations at Risk; Preventive; Rattus; Recovery; Reporting; Research; Rodent; Rural Community; Rural Population; Sampling; Serum; Site; Soil; Source; Surface; Techniques; Time; Tissues; Toxic effect; Toxicology; Translating; Uranium; Urine; Vacuum; Vanadium; Variant; Water; Work; community center; cost; detection limit; improved; in vivo; interest; liver injury; metal poisoning; minimally invasive; programs; remediation; remote monitoring; reproductive; toxic metal; wasting

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.

量化间隙液中的重金属，以远程监测慢性暴露 摘要/摘要 长期暴露于重金属（HM）与许多有害的健康影响有关。嗯 土壤和水的污染每年为美国和全球经济成本数万亿美元 修复和健康费用。 HM污染与西方人的人类健康特别相关 美国包括铀（U），镉（CD），钒（V）和砷（AS）。毒性可以归因于 单个HMS，但是怀疑会接触多个HMS 健康影响。虽然几项研究描述了这些的地表水和沉积物含量 有毒金属，由于需要收集血液或尿液，确定生物负荷仍然受到挑战 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表明一种微创方法 可以适应以监测局部和 分散的社区。 ISF可以用微针阵列（MA）收集，并且是丰富的来源 疾病和暴露生物标志物。 我们最终设想了可穿戴的微针贴片，可以邮寄给个人或分发 通过社区中心。这些补丁将磨损几个小时，然后返回到 中央实验室测量ISF HM水平。该项目的中心假设是MA提取 ISF的最低侵入性定量HM暴露将是高度稳定的度量 用于暴露评估。 当前项目的目的是1）建立用于ICP-MS HMS分析的分析参数 MA提取的ISF，2）量化ISF与尿液的基线HM含量意外 种群和3）通过定义HM之间的关系来表征混合的HM暴露模型 随着时间的流逝，ISF，血液和尿液中的浓度。 这项工作直接与NIEHS的使命保持一致，“发现环境如何影响人们 为了通过开发最小侵入性的纵向生物监测方法来促进更健康的生活”。 这个高度翻译的项目可以提高对HM生物分布的基本理解 开发一个可以提供可行数据以增强预防性健康和的监视平台 修复工作。