Abstract

Continuous monitoring of glucose levels has improved diabetes therapy. Current approaches rely on enzyme-linked electrochemical probes but do not allow a fully autonomous artificial pancreas. In contrast, monitoring the activity of a few electrogenic pancreatic islets in a biosensor may harness the computational power of the different endocrine cell types in the micro-organ, shaped for nutrient detection during evolution, and provide a more appropriate read-out. Extracellular electrophysiology captures slow potentials (SPs), which reflect coupled islet {beta}-cell activity and is thus a method of choice for long-term monitoring of native islet activity in vitro. We have now developed a microfluidic microelectrode chip containing a few islets and linked to interstitial fluids in live rats by subcutaneous microdialysis. The electrical activity in terms of slow potentials monitored by this biosensor reacts ex vivo proportionally to glucose levels off-line in serum or dialysed interstitial fluid. On-line monitoring in vivo reveals an excellent correlation between islet slow potential frequency, and to a lesser degree to slow potential amplitudes, to glucose concentrations with little variation between animals. The microorgan-based biosensor harness multiple parameters in vivo and provides a read-out closer to physiology. This demonstrates the usefulness of such biosensors for sensor-based therapy of diabetes.