MXene/PEDOT Functional Coatings on Flexible Microelectrode Arrays for Multianalyte In Vivo Neurochemical Sensing and Electrophysiology

MXene‐based coatings offer a promising route to multifunctional neural interfaces for in vivo neurochemical sensing. Here, we develop Ti 3 C 2 T x MXene/poly(3,4‐ethylenedioxythiophene) (MXene/PEDOT) composite coatings for glassy carbon (GC) and platinum (Pt) flexible microelectrode arrays (MEAs), enabling multianalyte neurochemical sensing and electrophysiological recording. MXene/PEDOT forms uniform nanostructured films that increase charge storage capacity by one order of magnitude, reduce impedance by ∼84% at 1 kHz, and enhance charge transfer efficiency for square‐wave voltammetry (SWV). Using an optimized SWV waveform, functionalized GC‐MEAs detect dopamine (DA) and serotonin (5‐HT) individually and simultaneously with low limits of detection (9.6 n M for DA; 4.7 nM for 5‐HT), high selectivity, and exceptional resistance to electrochemical fouling (>120 h DA; >40 h 5‐HT) and biofouling. In vivo measurements resolve basal extracellular DA in the striatum (99 ± 29 nM) and 5‐HT in the amygdala and prefrontal cortex (20 ± 7 n M ), with their simultaneous striatal detection validated by pharmacological manipulation of neurotransmitter levels. Extending this strategy to Pt‐MEAs confers neurochemical sensitivity while preserving single‐unit recordings, establishing MXene/PEDOT as a versatile functional coating for multimodal, multianalyte interfaces.