Rapid neurostimulation at micron scale with optically controlled thermal-capture technique

Precise control of cellular temperature at the microscale is crucial for developing novel neurostimulation techniques. Here, we study the effect of local heat on the electrophysiological properties of cells at the subcellular level using a cutting-edge micrometer-scale thermal probe, the diamond heater-thermometer (DHT). Experiments on primary neuronal cultures and HEK293 cells revealed that millisecond heat pulses could induce reversible changes in membrane potential and elicit ionic displacement currents. At local temperatures close to 50 °C, a rapid increase in cellular response by an order of magnitude was observed, attributed to local phase changes in the phospholipid membrane at the point of contact with the DHT. This allows the cell membrane to be effectively and reproducibly captured by temperature, referred to as thermal-capture mode (TCM). Once transition to TCM occurred, even lower temperatures (<35 °C) elicited depolarization up to 10 mV in neurons, sufficient for triggering action potentials with rates up to 30 Hz. Additionally, the impact of high temperatures beyond the physiological range on the electrophysiology of the cell was assessed. These findings enhance the understanding of how local heat affects cellular functions and provide insights into the thermal modulation of cell activity.