Abnormal regulation of molecules such as hormones and neurotransmitters that are secreted from cells in the human body leads to a wide range of debilitating conditions, including addiction, depression, diabetes and many others. A major challenge in understanding the normal and abnormal regulation of hormone and neurotransmitter secretion is the inability to measure these molecules with sufficient selectivity and sensitivity as they are released from cells. This research project aims to overcome this challenging by developing a new biomimetic sensor platform that can measure the secretion of a wide range of important hormones and neurotransmitters that are biologically important, but that cannot be detected adequately using currently existing methods. The capability to make such measurements enables the research community to better understand, and ultimately correct, the underlying biochemical mechanisms in hormone and neurotransmitter regulation. The project provides educational and interdisciplinary research opportunities for undergraduate and graduate students at the University of Arizona (a Hispanic Serving Institution) and Yavapai Community College, thereby helping to build a diverse science, technology, engineering and mathematics workforce. The development of sensors that are capable of detecting various single chemical compounds, as well as multiple chemical compounds released simultaneously, from cells has proven challenging for the vast majority of hormones and neuropeptides, and many neurotransmitters. This research project addresses the critical need for new, label-free measurement strategies for hormones and neurotransmitters by developing a novel class of electrophysiological sensors based upon a new sensor transducer concept that is readily modified to enable detection of a wide range important biochemical analytes. These electrophysiological sensors are comprised of protein transducers that generate a high-gain electrical signal upon analyte binding, including ion channel proteins or ion channel-coupled receptor proteins. The transducers are embedded in an ultrastable lipid membrane that is integrated into a micropipette architecture. In addition to single analyte sensors, sensors comprised of multiple, differing sensor elements that enable quantification of multiple analytes are being developed. This sensor platform provides a modular approach for developing highly sensitive and selective sensors with high spatial and temporal resolution. The project focuses on development and characterization of biomimetic electrophysiological sensors with emphasis on key variables that affect sensor function and performance. The work targets optimization of lipid membranes and protein transducers, the design of multianalyte sensors and performance evaluation in model cellular systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.