Direct electrochemical modulation of the membrane potential enables insulin secretion control in pancreatic β-cells cultured on electrodes

Interfaces that convert digitally defined signals into biological analog functions (D/A biointerfaces) remain underdeveloped compared with biosensors that digitize biological analog information (A/D biointerfaces). Here, we report direct electrochemical control of insulin secretion through membrane-potential modulation using a stable tetraethyl orthosilicate (TEOS)-incorporated PEDOT:PSS electrode that supports long-term culture of pancreatic β-cells as a model endocrine system. β-cells expressing luminescent insulin (iGL cells) were cultured on the electrode, and secretion dynamics were monitored by luminescence imaging during potential application. Application of +500 mV relative to the resting electrode potential (REST) rapidly reduced luminescence, indicating insulin release within seconds. Following this potential application, cells remained viable after additional culture for 3 days, retaining insulin synthesis and the ability to respond to subsequent induction. Fluorescence imaging with the membrane-potential dye FluoVolt™ suggested that the application of REST +200 mV induced depolarization comparable to that generally reported for activation of voltage-gated Ca²⁺ channels. Following a brief induction period, reapplication of the REST potential halted secretion. Alternating induction and REST pulses enabled stepwise modulation of cumulative insulin release. These results provide a basic operational principle for D/A biointerfaces that translate digitally programmed electrochemical inputs into analog, graded hormonal outputs.