Real-time multi-channel measurements of tonic
serotonin (5-hydroxytryptamine, 5-HT) concentrations across different brain regions are of utmost importance to the understanding of 5-HT’s role in anxiety, depression, and
impulse control disorders, which will improve the diagnosis and treatment of these neuropsychiatric illnesses. Chronic sampling of
5-HT is critical in tracking disease development as well as the time course of pharmacological treatments. Despite their value, in vivo chronic multi-site measurements of
5-HT have not been reported. To fill this technological gap, we batch fabricated implantable glassy
carbon (GC)
microelectrode arrays (MEAs) on a flexible SU-8 substrate to provide an electrochemically stable and biocompatible device/tissue interface. Then, to achieve multi-site detection of tonic
5-HT concentrations, we incorporated the poly(3,4-ethylenedioxythiophene)/functionalized
carbon nanotube (PEDOT/CNT) coating on the GC
microelectrodes in combination with a new square wave voltammetry (SWV) approach, optimized for selective
5-HT measurement. In vitro , the PEDOT/CNT coated GC
microelectrodes achieved high sensitivity towards
5-HT, good fouling resistance in the presence of
5-HT, and excellent selectivity towards the most common neurochemical interferents. In vivo , our PEDOT/CNT-coated GC MEAs were able to successfully detect basal
5-HT concentrations at different locations of the CA2 hippocampal region of mice in both anesthetized and awake head-fixed conditions. Furthermore, the implanted PEDOT/CNT-coated MEA achieved stable detection of tonic
5-HT concentrations for one week. Finally, histology data in the hippocampus shows reduced tissue damage and inflammatory responses compared to stiff
silicon probes. To the best of our knowledge, this PEDOT/CNT-coated GC MEA is the first implantable flexible multisite sensor capable of chronic in vivo multi-site sensing of tonic
5-HT. This implantable MEA can be custom-designed according to specific brain region of interests and research questions, with the potential to combine electrophysiology recording and multiple analyte sensing to maximize our understanding of neurochemistry.
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