BME PhD Final Exam Announcement for Emma Vanderlaan (S. Harbin, advisor) Everyone is invited to attend the public presentation beginning at 1:00 pm. Title: Engineering Design of Novel 3D Microphysiological System and Sensor for Functional Assessment of Pancreatic Beta-Cells Date: March 1, 2023 Time: 1:00 pm Location: MJIS 2001 and Zoom https://purdue-edu.zoom.us/j/94439715488?pwd=aElCdCt2VElmUHlMK3ZBQmF6WDZQdz0... Meeting ID: 944 3971 5488 Passcode: 943658 Thesis Committee: Dr. Sherry Harbin (advisor) Dr. Carmella Evans-Molina (clinical co-advisor) Dr. Hyowon Lee Dr. Adrian Buganza Tepole Dr. Luis Solorio Abstract: Diabetes, a chronic condition characterized by elevated blood glucose levels, arises when pancreatic β-cells lose capacity to produce a robust, dynamic glucose-stimulated insulin secretion (GSIS) response. Accurate measurement of β-cell health and function ex vivo is thus fundamental to diabetes research, including studies evaluating disease mechanisms, novel drug candidates, and replacement β-cell populations. However, present-day dynamic GSIS assays typically represent end-point measurements, involve expensive commercial perifusion machines, and require time-consuming enzyme-linked immunosorbent assays (ELISA) for insulin detection. Microfluidic devices developed as accessible, low-cost alternatives still rely on secondary ELISAs and suspend islets in liquid medium, limiting their survival in vitro. Here, we present a novel, 3D-printed microphysiological system (MPS) designed to recreate components of in-vivo microenvironments through encapsulation in fibrillar type I collagen and restoration of favorable molecular transport conditions. Following computational-informed design and rapid prototyping, the MPS platform sustained collagen-encapsulated mouse islet viability and cytoarchitecture for 5 days and supported in situ measurements of dynamic β-cell function. To rapidly detect insulin secretion from β-cells in the MPS, we then developed a highly sensitive electrochemical sensor for zinc (Zn2+), co-released with insulin, based on glassy carbon electrodes modified with bismuth and indium and coated with Nafion. Finally, we validated sensor detection of Zn2+ released from glucose-stimulated INS-1 β-cells and primary mouse islets, finding high correlation with insulin as measured by standard ELISA. Together, the 3D MPS and Zn2+ sensor developed in this dissertation represent novel platforms for evaluating dynamic β-cell function in a low-cost, user-friendly, and physiologically-relevant manner.