Organotypic Neurovascular Unit and Electrochemical Platform for Predictive Toxicology

Tuesday, 15 October 2019: 11:40
Room 313 (The Hilton Atlanta)
D. R. Miller, E. S. McClain, J. A. Brown, J. C. May, J. Wikswo, J. A. McLean, and D. E. Cliffel (Vanderbilt University)
Organophosphates account for about a third (nine million kilograms in 2012) of all pesticides used in the U.S., yet are toxic to humans, with exposure leading to neurodegenerative disorders and death. The ability to identify organophosphate exposure and predict biological responses has been limited—with epidemiological studies being uncontrolled and murine studies being discordant—leaving critical questions unanswered. In my talk, I will present a platform that uses human-derived cells to form a model blood-brain barrier to perform controlled toxicological studies. As a proof-of-concept experiment, environmental exposure was simulated by adding chlorpyrifos (CPF), the most prevalent organophosphate used in the U.S., to the vascular side of this engineered blood-brain barrier unit. Then, chemical perturbations were probed using a combination of electrochemical assays and mass spectrometry. The substantial metabolic disruption induced by this commercial pesticide will be discussed as well as platform advances (microfluidics and sensors) that made the experiments possible. Broadly, this work may lead to early diagnosis of CPF exposure and inform policies around pesticide use.