Temporal interference stimulator realized with silicon chip for non-invasive neuromodulation

Abstract Objective. Temporal interference stimulation (TIS) has emerged as an innovative and promising approach for non-invasive stimulation. While previous studies have demonstrated the efficacy and performance of TIS using benchtop instruments, a dedicated system-on-chip for TIS applications has not yet been reported. This work addresses this gap by presenting a design for a TIS chip that enhances portability, thereby facilitating wearable applications of TIS. Approach. A miniaturized dual-channel temporal interference stimulator for non-invasive neuro-modulation is proposed and fabricated in a 0.18 µ m CMOS BCD process. The TIS chip occupies the silicon area of only 2.66 mm 2 . It generates output signals with a maximum amplitude of ±5 V and reliable frequency, with programmable input parameters to accommodate diverse biomedical applications. The carrier frequencies of the generated signals include 1 kHz, 2 kHz, and 3 kHz, combined with beat frequencies of 5 Hz, 10 Hz, and 20 Hz. This results in a total of nine available operation modes, enabling effective TIS. Main results. The proposed chip has effectively generated temporally interfering signals with reliable frequency and amplitude. To validate the efficacy of the TIS chip, in-vivo animal experiments have been conducted, demonstrating its ability to produce effective electrical stimulation signals that successfully elicit neural responses in the deep brain of a pig. Significance. This work has replaced the bulky external stimulator with a fully integrated silicon chip, significantly enhancing portability and supporting future wearable clinical applications.