Potential of Photoelectric Stimulation with Ultrasmall Carbon Electrode on Neural Tissue: New Directions in Neurostimulation Technology Development

Abstract Neuromodulation technologies have gained considerable attention for their clinical potential in treating neurological disorders and advancing cognition research. However, traditional methods like electrical stimulation and optogenetics face technical and biological challenges that limit their therapeutic and research applications. A promising alternative, photoelectric neurostimulation, uses near‐infrared light to generate electrical pulses and thus enables stimulation of neuronal activity without genetic alterations. This study explores various design strategies to enhance photoelectric stimulation with minimally invasive, ultrasmall, untethered carbon electrodes. Employing a multiphoton laser as the near‐infrared (NIR) light source, benchtop experiments are conducted using a three‐electrode setup and chronopotentiometry to record photo‐stimulated voltage. In vivo evaluations utilize Thy1‐GCaMP6s mice with acutely implanted ultrasmall carbon electrodes. Results highlighted the beneficial effects of high duty‐cycle laser scanning and photovoltaic polymer interfaces on the photo‐stimulated voltages by the implanted electrode. Additionally, the promising potential of carbon‐based diamond electrodes are demonstrated for photoelectric stimulation and the application of photoelectric stimulation in precise chemical delivery by loading mesoporous silica nanoparticles (SNPs) co‐deposited with polyethylenedioxythiophene (PEDOT). Together, these findings on photoelectric stimulation utilizing ultrasmall carbon electrodes underscore its immense potential for advancing the next generation of neurostimulation technology.