A microfluidic twin islets-on-chip device for on-line electrophysiological monitoring

Abstract

Pancreatic islets play a major role in glucose homeostasis as well as in diabetes, and islets-on-chip devices have been mainly developed using optical means for on-line monitoring. In contrast, no well-characterized electrophysiological platform for on-line analysis with unrivalled temporal resolution has been reported. Extracellular electrophysiology monitors two crucial parameters, islet β-cell activity and β-to-β-cell coupling, does not require chemical or genetic probes with inherent potential bias, is non-invasive and permits repetitive long-term monitoring. We have now developed and characterized a microfluidic islets-on-chip for combined electrophysiology (on-line) and hormone monitoring (off-line) with two chambers for concomitant monitoring. Fabrication of the device, based on commercial or easily manufacturable components, is within the reach of non-specialized laboratories. The chip permits convenient loading as well as long-term culture with comparable glucose kinetics and low shear stress in both chambers. An optimized flow rate did not alter islet β-cell electrical activity or coupling in response to glucose. Culturing for up to 8 days did not change islet survival as well as glucose-induced electrical or secretory kinetics of islet β-cells. The addition of a physiological amino acid mix, in the presence of elevated glucose, made a considerable change in the functional organisation of islet β-cell activity in terms of frequency and coupling, which explains the ensuing strong increase in insulin secretion. This device thus allows reliable long-term multiparametric on-line monitoring in two islet populations. The ease of fabrication, assembly and handling should permit widespread long-term on-line monitoring of islet activity in native micro-organs (e.g. controls/mutants), pseudo-islets or stem-cell-derived islet-like organoids.