Chemically Selective Nanoelectrode Arrays for Real-Time, Parallel Neurotransmitter and Electrical Recording

Electrical activity and neurotransmitter release are tightly coupled in neurons, but co-registered measurements of both modalities from the same subcellular site in real time have remained difficult. Bridging this gap is essential for linking single-cell processing to network dynamics and for enabling closed-loop neural interfaces. Here, we introduce Graph-nanoelectrode arrays (NEAs), graphite-modified nano-electrode arrays that unify intracellular-like electrophysiology with electrochemical neurotransmitter sensing. Graph-NEAs record supra- and sub-threshold electrical activity together with dopamine release currents from sub-neuronal locations in live neuron-like networks, with high sensitivity, selectivity, and stability. Using a single multimodal setup, we validate chemical readouts against calcium imaging and electrical signals and show that dopamine dynamics closely track sub-threshold electrical activity across seconds with electrical stimulation or potassium chloride, and across minutes with vesicular transporter inhibition by reserpine. We further recapitulate Parkinson's-relevant oxidative stress through chronic glutathione depletion using buthionine sulfoximine or prolonged iron exposure. An optical synaptic vesicle assay confirms that the chemical currents originate from neurotransmitter release at the cell-nanoelectrode interface. By unifying chemical and electrical sensing within the same nanoscale platform, Graph-NEAs establish a new paradigm for multimodal neural recording with applications in closed-loop neuromodulation, disease modelling, drug discovery, and neuromorphic engineering.