Nongenetic Photostimulation of hiPSC Neurons Using Plasmonic Nanopyramids

Human-induced pluripotent stem cell (hiPSC)-derived neurons offer a powerful platform for replicating key aspects of human neurodevelopment, synaptic connectivity, and ion channel expression. However, their electrophysiological investigation remains challenging, particularly for studies aiming to elicit neuronal activity with minimal perturbation of physiological conditions. In this study, we integrated plasmonic gold pyramids onto commercial titanium nitride (TiN) microelectrode arrays (MEAs). The presence of these plasmonic structures enhanced the generated photocurrent by more than 30-fold and simultaneously reduced the electrode impedance by approximately 6-fold. Leveraging the unique optical properties of plasmonic nanostructures, we demonstrate that gold pyramids enable efficient neuronal photostimulation at low light intensities with minimal perturbations. Our approach combines nongenetic optical stimulation with high-resolution electrophysiological recording, providing precise spatiotemporal control of neuronal activity. These advances highlight the potential of our plasmonically enhanced MEA technology to bridge the gap between preclinical research and human neurological applications.