Towards Closed-Loop Neuromodulation for Type 2 Diabetes With Ex Vivo Validation of Beta-Cell Activity and FOPP Detection

We present in this paper an implantable closed-loop neuromodulation prototype system for type 2 diabetes (T2D) management, which leverages pancreatic electrophysiology as both a sensing and therapeutic modality. Among candidate biomarkers, the fraction of plateau phase (FOPP) emerges as a robust indicator of glucose dynamics. Hence, the neural interface is optimized for low-power measurement of the electrical activity of the beta-cells with high accuracy in direct readout mode and long-term monitoring in FOPP mode. The experimental framework was established using a perfused pancreas model, first in mice and then optimized for rats, with glucose-dependent signals captured via a custom 16-channel neural interface. Results confirmed the feasibility of extracting FOPP in ex vivo settings, though signal complexity differed from isolated islets in vitro. Additionally, a fabricated 8-channel electrical stimulator with adjustable current levels and optimized charge balancing technique, demonstrated the capability to meet physiological requirements for beta-cell activation. While integration of AI-based classifiers for advanced FOPP-glucose correlation remains a future step, this study establishes the foundational experimental and technological evidence for a next-generation closed-loop neuromodulator.