SCHEPHERD: A universal platform for high-throughput, high-resolution, and programmable control of cell behavior through bioelectric stimulation

Spanning frogs, fish, and humans, direct-current (DC) bioelectric cues play critical roles beyond neuro-muscular function, such as modulating morphogenesis, immune response, and healing through electrotaxis--electrically directed cell migration. Harnessing this potential requires new tools. However, standardized, accessible, and reproducible infrastructure capable of DC stimulation remains a challenge. We present SCHEPHERD: a universal, electrobioreactor integrating 8 stimulation channels and modular inserts to enable most electrotaxis assays in one device (cells, monolayers, and 3D spheroids), while enabling powerful, new capabilities. SCHEPHERD revealed through parameter sweeps that DC fields act like a steering wheel and gas pedal for cell migration. We then used live confocal imaging to observe electrically reprogrammed F-actin dynamics. Finally, our multi-polar inserts generated complex spatial electrical patterns that reorganize engineered tissue dynamics. By significantly improving accessibility through modularity and an open-source, graphically programmed stimulator, we hope SCHEPHERD can help broaden the community studying these important DC bioelectric phenomena.