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

<i>Objective.</i>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.<i>Approach.</i>A miniaturized dual-channel temporal interference stimulator for non-invasive neuro-modulation is proposed and fabricated in a 0.18<i>µ</i>m CMOS BCD process. The TIS chip occupies the silicon area of only 2.66 mm². 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.<i>Main results.</i>The proposed chip has effectively generated temporally interfering signals with reliable frequency and amplitude. To validate the efficacy of the TIS chip,<i>in-vivo</i>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.<i>Significance.</i>This work has replaced the bulky external stimulator with a fully integrated silicon chip, significantly enhancing portability and supporting future wearable clinical applications.