Miniaturized Iontronic Micropipettes for Precise and Dynamic Ionic Modulation of Neuronal and Astrocytic Activity

Abstract The composition of the extracellular milieu can vary significantly under physiological and pathological conditions, thereby altering the functional set point of brain cells. While global changes in the extracellular milieu are known to affect network activity, a detailed understanding of how specific changes in ion species impact individual cells remains elusive. Current modulation methods involve the use of diluted salts, such as KCl, where lack of precise control complicates data interpretation. This study achieves enhanced resolution by using a miniaturized iontronic micropipette. The micropipette, with a tip filled with polyelectrolyte and an outlet size below 2 µm, allows for on‐demand ionic manipulation of single cells, without simultaneous co‐delivery of solvents or other solutes. Electrical, chemical, and optical characterizations, supported by computational modeling, confirm the device's high spatial and temporal precision. Validated in hippocampal slices, the device demonstrates iontronic release of potassium ions (K⁺), with a low current (<200 nA), that effectively, rapidly, and reversibly modulates individually targeted neurons and astrocytes. These findings underscore the potential of iontronic micropipettes to elucidate the distinct responses of neuronal and glial cells to specific changes in the local extracellular milieu, offering insights for neuroscience research and therapeutic innovation.