Flexible Multimodal Neural Probe with Integrated Three-Electrode Aptameric Sensing for In Vivo Monitoring of Dopamine Dynamics and Neural Activity
Abstract
Neural function emerges from the interplay between electrical activity and neurochemical signaling, yet most implantable neural interfaces primarily record electrophysiological signals and lack molecular specificity for neurotransmitter monitoring. Here, we developed a flexible multimodal neural probe integrating an on-chip three-electrode electrochemical aptamer sensor with electrophysiological recording sites for combined monitoring of extracellular dopamine (DA) dynamics and neuronal activity. Fabrication of the electrochemical interface was systematically optimized by controlling gold nanostructure (AuNS) electrodeposition from 0.50 to 0.70 V. Electrodeposition at 0.65 V provided the best balance between increased electrochemically active surface area (ECSA), surface morphology, fabrication reproducibility, and electrical isolation, yielding an approximately 4.7-fold ECSA enhancement with a probe-to-probe coefficient of variation (CV%) of 2.02%. A methylene blue-labeled DA aptamer was assembled onto the AuNS working electrodes for sequence-specific molecular recognition, while integrated Ag/AgCl reference and nanostructured platinum counter electrodes completed the on-chip sensing system. Electrochemical impedance analysis further demonstrated reproducible interfacial characteristics following stepwise functionalization. The electrophysiological electrodes exhibited a mean impedance of 366.02 ± 18.63 kΩ at 1 kHz with an interprobe CV% of 5.09%. Square-wave voltammetry…
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