Label-Free Optical Sensor for Real-Time Monitoring of Insulin Secretion from Single Human Pancreatic Islets

Glucose-stimulated insulin secretion is the central functional readout of pancreatic islets, yet existing assays often require offline processing or pooling of multiple islets, limiting real-time assessment of single-islet function. Here we report a microscopy-compatible islet-on-a-chip (IOC) integrated with light scattering-based broadband backscattering confocal microscopy (BBCM) for continuous, label-free optical readout of insulin secretion dynamics in functional human islets. Fabricated using two-photon polymerization, the IOC-BBCM sensor stabilizes single human islets under continuous perfusion for high-resolution optical interrogation. The sensor identifies insulin-rich β-cells label-free, as confirmed by insulin immunostaining, and monitors granule depletion and redistribution during glucose and potassium chloride (KCl) stimulation, matching ELISA-quantified insulin secretion from the same perfused islets. This modular sensor provides a non-destructive, label-free approach for monitoring stimulus-linked secretion dynamics from individual human islets and should support longitudinal studies of islet function.