Thermo-plasmonic effect based neural stimulation has been suggested as an alternative optical neural stimulation technology without genetic modification. Integration of near infrared light with plasmonic gold nanoparticles has been demonstrated as a neuromodulation tool on in vitro neuronal network models. In order to further test the validity of the thermo-plasmonic neural stimulation across multiple biological models (in vitro, ex vivo, and in vivo) avoiding genetic modification in optical neuromodulation, versatile engineering approaches to apply the thermoplasmonic effect would be required. In this work, we developed a gold nanorod attached optical fiber technology for the localized neural stimulation based on thermo-plasmonic effect. A simple fabrication process was developed for efficient nanoparticle coating on commercial optical fibers. The thermo-plasmonic optical fiber proved that it can locally modulate the neural activity in vitro. Lastly, we simulated the spatiotemporal temperature change by the thermo-plasmonic optical fiber and analyzed its applicability to in vivo animal models.

Objective. Photothermal neural stimulation has been developed in a variety of interfaces as an alternative technology that can perturb neural activity. The demonstrations of these techniques have heavily relied on open-loop stimulation or complete suppression of neural activity. To extend the controllability of photothermal neural stimulation, combining it with a closed-loop system is required. In this work, we investigated whether photothermal suppression mechanism can be used in a closed-loop system to reliably modulate neural spike rate to non-zero setpoints. Approach. To incorporate the photothermal inhibition mechanism into the neural feedback system, we combined a thermoplasmonic stimulation platform based on gold nanorods (GNRs) and near-infrared illuminations (808 nm, spot size: 2 mm or 200 μm in diameter) with a proportional-integral (PI) controller. The closed-loop feedback control system was implemented to track predetermined target spike rates of hippocampal neuronal networks cultured on GNR-coated microelectrode arrays. Main results. The closed-loop system for neural spike rate control was successfully implemented using a PI controller and the thermoplasmonic neural suppression platform. Compared to the open-loop control, the target-channel spike rates were precisely modulated to remain constant or change in a sinusoidal form in the range below baseline spike rates. The spike rate response behaviors were affected by the choice of the controller gain. We also demonstrated that the functional connectivity of a synchronized bursting network could be altered by controlling the spike rate of one of the participating channels. Significance. The thermoplasmonic feedback controller proved that it can precisely modulate neural spike rate of neural activity in vitro. This technology can be used for studying neuronal network dynamics and might provide insights in developing new neuromodulation techniques in clinical applications.

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