A Miniaturized and Flexible Ultrasound-driven Intracranial Brain Stimulator for Neuromodulation Applications

OBJECTIVE: Conventional brain stimulators primarily rely on implantable batteries, necessitating repeated replacement surgeries. Ultrasound-driven stimulators offer a promising wireless alternative, yet existing systems are predominantly extracranial and face limitations in stability and efficiency. Here, we fabricated a miniaturized, implantable ultrasound-driven intracranial brain stimulator (UIBS), achieving stable and efficient neuromodulation. METHODS: The UIBS was developed by integrating a flexible composite structure consisting of PVDF-TrFE and a flexible acoustic matching layer with a rectifier circuit embedded in a PEEK structure. Additionally, transcranial ultrasound transmission was optimized through numerical simulations and experimental validation. Electrical output performance, the electrolysis-defined safety window, and neuromodulation efficacy as well as biocompatibility following UIBS implantation into the rat primary somatosensory cortex were systematically assessed. RESULTS: The optimal transcranial ultrasound frequency was determined to be 1.5 MHz. Driven by transcranial ultrasound at 2 MPa, the UIBS generated a rectified output voltage exceeding 1.3 V, with a safe electrolysis duration exceeding 10 seconds at 100 Hz. Furthermore, in vivo experiments demonstrated that under ultrasound driving, the device can be stably implanted and reliably evoke neural activity in the primary somatosensory cortex, while maintaining good biosafety. CONCLUSION: This work presents a novel and miniaturized UIBS, enabling effective intracranial energy harvesting and precise neuromodulation, addressing key constraints of battery-dependent and extracranial devices.