Diabetachip: Organ-on-Chip for a Novel Cell-Based Biosensor in Pretransplantation Quality Control and in Treatment of Type 1 Diabetes

Raoux, Matthieu ;   Lebreton, Fanny ;   Pedraza, Eileen ;   Bornat, Yannick ;   Floderer, Jean-Baptiste ;   Catargi, Bogdan ;   Renaud, Sylvie ;   Lang, Jochen

Continuous glucose monitoring sensors only recognize glucose but no other hormones, they can therefore not work as a closed loop and require diverse algorithm to approach the complexity of life. In addition, no non-invasive method has been established to monitor human islets prior to transplantation as performed in certain cases of type 1 diabetes, or during differentiation of stem cells. We have now conceived a novel biosensor device based on the electrical activity of islets, their first integrative signal reflecting the demand in insulin, and acquisition system of islets (Diabetachip) capable to process 60 channels online and in real time. Islets (murine or human donor ones) were cultured directly on micro-electrode arrays for up to a week. Output signals were digitally converted and processed in real time using digital integrated circuits specifically designed, integrated on a custom electronics board. Digital filters embedded on integrated circuits perform signal frequency separation. Embedded digital electronics also optionally computes amplitudes, frequencies and statistics on individual signals. We have been able to micropattern islet cells to the microelectrodes. Human donor islets exhibit a glucose-dependent increase in activity that contains rapid action potentials (APs) as well as slower oscillations (slow waves) and is stable for at least 24 h. As shown here, our approach is valid for human islets.