Metals are ubiquitous in the environment and have long been recognized to pose significant threats to hu- man health. Blood lead (Pb) has been consistently associated with deficits in IQ and academic achievement in numerous controlled studies. Manganese (Mn) is an essential element, yet neurotoxic in excess, capable of crossing the blood-brain barrier and accumulating in the brain. Current approaches for measuring such exposures suffer from high costs including extensive labor, equipment and time-consuming laboratory procedures, and often, demonstrate long turnaround times. Hence, there is a critical need for improved technology to quantitatively assess levels and identify adverse consequences of these exposures. Our preliminary data show feasibility of measuring of Mn and Pb metals with point-of-care sensors. We therefore propose to demon- strate rapid, point-of-care, multi-analyte assessment of Mn and Pb metals in a finger prick of blood from children. In the R21 phase, we will demonstrate sensor validity and usability for metal analysis in whole blood. The feasibility of the sensor has been established in our prior work.
In Aim 1, we will firs demonstrate ability to ac- accurately and reliably measure Mn and Pb metals in blood under real-world conditions with appropriate specific- ty and sensitivity. Then, we will demonstrate ability to scale-up manufacturing of sensors for the study in the R33 phase.
In Aim 2, we will develop a streamlined, user-friendly software interface. Finally, we will assess usability of the sensor and supporting documentation by seeking feedback from experts and study staff. We will demonstrate the ability for sensors to be used with minimal oversight and establish strategies for data analysis and deployment. The R33 phase will further demonstrate the added scientific value.
In Aim 3 we will deploy the sensor in longitudinal cohort of adolescent children to evaluate the relationship between traditional and novel internal dose markers of metals (Mn and Pb) and neuromotor performance. We will evaluate the novel hypothesis that Mn and Pb will significantly impact functional gait and static and dynamic balance in an adolescent cohort. Additionally, we propose a high risk/high benefit aim to evaluate the clinical significance of unbound or free Mn in whole blood as a novel biomarker for Mn.
In Aim 4 we will develop effective participant report-back mecha- nisms to return blood metal results. The R33 phase will culminate with the development of ethical strategies for effective mechanisms for reporting measurement results back to study participants. A relatively swift, simultaneous assessment of heavy metal exposure, which ultimately reduces costs and turnaround times, would benefit pediatric public health nationally and internationally. Indeed, our long-term goal is to use sensors to move blood analysis from the laboratory to the clinical setting, providing results within minutes.
This application seeks to demonstrate validity and usability of a 'laboratory-in-a-chip' sensor for rapid and accurate point-of-care measurement of metals (manganese and lead) in blood. Whole blood analysis is the most common method for determining metal exposure and assessment of health outcomes, yet multi-metal analysis and sample collection from children are highly problematic. The uniqueness of this study is the nature of the sensor, child-friendly requirement of only drops of blood per analysis, ability to conduct multiple blood measurements on site (point-of-care), and use in occupational and international research settings.
| Kang, Wenjing; Pei, Xing; Rusinek, Cory A et al. (2017) Determination of Lead with a Copper-Based Electrochemical Sensor. Anal Chem 89:3345-3352 |
| Kang, Wenjing; Rusinek, Cory; Bange, Adam et al. (2017) Determination of manganese by cathodic stripping voltammetry on a microfabricated platinum thin-film electrode. Electroanalysis 29:686-695 |
