A Fully-Integrated Wireless Ingestible CMOS Drug-Delivery Chip With Electrochemical Energy Harvesting and pH-Adaptive MPPT for Personalized Therapeutics

The rapid growth of personalized medicine has driven increased demand for battery-free, energy-efficient ingestible electronics for on-demand gastrointestinal (GI) drug delivery. This article presents the first fully-integrated, battery-free ingestible CMOS platform that harvests energy from a galvanic cell (GC) through a reconfigurable switched-capacitor converter, with pH-adaptive maximum power point tracking (MPPT) guided by on-chip gastric pH measurement. The system offers three clinically relevant drug-delivery modes, selectable via 13.56 MHz wireless RF commands: burst, low-energy dissolve, and balanced modes. Upon receiving a drug-delivery command, the system applies an optimal voltage bias according to the measured pH and selected delivery mode, to electrochemically dissolve a metal membrane and release the payload. Fabricated in a 65-nm CMOS, the 6-mm2chip integrates with a drug-delivery chamber, GC, and off-chip antenna to form a capsule that fits within the dimensions of commercial ingestible electronics. Ex vivo and in vitro tests demonstrate reliable system operation, with a 6-cm RF detection range from the tissue surface, 0.32-pH sensor resolution, and 72% end-to-end energy-harvesting efficiency with a wide range of input powers from 30 to$200~\mu $W. By integrating pH-adaptive MPPT with RF-controlled multimode drug release on a single platform, this work advances adaptable, responsive, and patient-specific therapies for GI drug delivery.