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.

PROJECT NARRATIVE This project will improve the understanding of heavy metal toxicity in humans and animals through minimally-invasive collection of interstitial fluid with microneedle arrays. It uses a chronic, mixed-metal exposure model that relates to real-world exposure to the metals found in mine wastes. It will further develop a monitoring platform that allows for non-destructive, longitudinal measurement of heavy metal exposure in at-risk populations.