02553nas a2200301   4500000000100000000000100001008004100002260001500043100002400058700002100082700002200103700001400125700002000139700002500159700002200184700002000206700002000226700002600246700002200272700002100294700002100315245013600336856007000472300001400542490000700556520167400563022001402237       2019                            d  c2019-09-101 aAaron L. Glieberman1 aBenjamin D. Pope1 aJohn F. Zimmerman1 aQihan Liu1 aJohn P. Ferrier1 aJennifer H. R. Kenty1 aAdrian M. Schrell1 aNikita Mukhitov1 aKevin L. Shores1 aAdrian Buganza Tepole1 aDouglas A. Melton1 aMichael G. Roper1 aKevin Kit Parker00aSynchronized stimulation and continuous insulin sensing in a microfluidic human Islet on a Chip designed for scalable manufacturing  uhttps://pubs.rsc.org/en/content/articlelanding/2019/lc/c9lc00253g  a2993-30100 v193 aPancreatic β cell function is compromised in diabetes and is typically assessed by measuring insulin secretion during glucose stimulation. Traditionally, measurement of glucose-stimulated insulin secretion involves manual liquid handling, heterogeneous stimulus delivery, and enzyme-linked immunosorbent assays that require large numbers of islets and processing time. Though microfluidic devices have been developed to address some of these limitations, traditional methods for islet testing remain the most common due to the learning curve for adopting microfluidic devices and the incompatibility of most device materials with large-scale manufacturing. We designed and built a thermoplastic, microfluidic-based Islet on a Chip compatible with commercial fabrication methods, that automates islet loading, stimulation, and insulin sensing. Inspired by the perfusion of native islets by designated arterioles and capillaries, the chip delivers synchronized glucose pulses to islets positioned in parallel channels. By flowing suspensions of human cadaveric islets onto the chip, we confirmed automatic capture of islets. Fluorescent glucose tracking demonstrated that stimulus delivery was synchronized within a two-minute window independent of the presence or size of captured islets. Insulin secretion was continuously sensed by an automated, on-chip immunoassay and quantified by fluorescence anisotropy. By integrating scalable manufacturing materials, on-line, continuous insulin measurement, and precise spatiotemporal stimulation into an easy-to-use design, the Islet on a Chip should accelerate efforts to study and develop effective treatments for diabetes.  a1473-0189