Spatiotemporal Cell Control via High-Precision Electronic Regulation of Microenvironmental pH

Accurate regulation of extracellular pH is crucial for controlling cell behaviors and functions. However, typical methods, which primarily rely on replacing cell culture media or using ionic diffusion, are slow, nondirectional, and lack spatiotemporal resolution. Here, we develop a microfabricated device that regulates microenvironmental pH within specific localized zones with high precision (uncertainty <0.1 pH units) and temporal resolution. The device uses a synchronization strategy that coordinates two processes: pulsatile modulation of pH through microelectrolysis and ultrasensitive graphene-electronic pH sensing, which operates in antiphase to the modulation. Using this device, we show real-time control of the dynamic behaviors of microscale clusters of bacteria (motility) and cardiomyocytes (calcium signaling and necrotic injury) in response to precisely regulated extracellular pH variations. Our device addresses the limitations of typical pH-altering techniques and holds significant potential to advance cell biology, physiology, tissue engineering, and regenerative medicine.