Flexible Glassy Carbon Multielectrode Array for In Vivo Multisite Detection of Tonic and Phasic Dopamine Concentrations

Abstract

Dopamine (DA) plays a central role in the modulation of various physiological brain functions, including learning, motivation, reward, and movement control. The DA dynamic occurs over multiple timescales, including fast phasic release, as a result of neuronal firing and slow tonic release, which regulates the phasic firing. Real-time measurements of tonic and phasic DA concentrations in the living brain can shed light on the mechanism of DA dynamics underlying behavioral and psychiatric disorders and on the action of pharmacological treatments targeting DA. Current state-of-the-art in vivo DA detection technologies are limited in either spatial or temporal resolution, channel count, longitudinal stability, and ability to measure both phasic and tonic dynamics. We present here an implantable glassy carbon (GC) multielectrode array on a SU-8 flexible substrate for integrated multichannel phasic and tonic measurements of DA concentrations. The GC MEA demonstrated in vivo multichannel fast-scan cyclic voltammetry (FSCV) detection of electrically stimulated phasic DA release simultaneously at different locations of the mouse dorsal striatum. Tonic DA measurement was enabled by coating GC electrodes with poly(3,4-ethylenedioxythiophene)/carbon nanotube (PEDOT/CNT) and using optimized square-wave voltammetry (SWV). Implanted PEDOT/CNT-coated MEAs achieved stable detection of tonic DA concentrations for up to 3 weeks in the mouse dorsal striatum. This is the first demonstration of implantable flexible MEA capable of multisite electrochemical sensing of both tonic and phasic DA dynamics in vivo with chronic stability.

Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels

“…GC MEAs were successfully fabricated using the high-resolution mask-less direct-writing photolithography process on SU-8 substrate that we previously reported (Castagnola et al 2022),…”

“…Furthermore, these experiments are typically performed at carbon fiber microelectrodes (CFEs), one site at a time (Abdalla et al 2017; Hashemi et al 2009; Saylor et al 2019; Yoonbae Oh 2016), while 5-HT dynamics are complex and differ in different brain regions or different loci of the same region, requiring high resolution multisite measurements (Kim et al 2005; Perez-Garcia and Meneses 2008). In the last few years, GC MEAs have been introduced as a multimodal platform for integrated multi-channel electrophysiological and electrochemical measurements for neural applications (Castagnola et al 2022; Castagnola et al 2021b; Castagnola et al 2018; Devi et al 2021; Nimbalkar et al 2018; Vahidi et al 2020; Vomero et al 2017). GC microelectrodes enable the integration of FSCV electrochemical sensing (Castagnola et al 2022; Castagnola et al 2021b; Castagnola et al 2018) to devices that are routinely used for multi-channel neurophysiological recordings and stimulation.…”

“…In the last few years, GC MEAs have been introduced as a multimodal platform for integrated multi-channel electrophysiological and electrochemical measurements for neural applications (Castagnola et al 2022; Castagnola et al 2021b; Castagnola et al 2018; Devi et al 2021; Nimbalkar et al 2018; Vahidi et al 2020; Vomero et al 2017). GC microelectrodes enable the integration of FSCV electrochemical sensing (Castagnola et al 2022; Castagnola et al 2021b; Castagnola et al 2018) to devices that are routinely used for multi-channel neurophysiological recordings and stimulation. However, although GC electrodes provides a superior electrochemical stability (Nimbalkar et al 2018; Vomero et al 2017) and improved coating adhesion (Castagnola et al 2017; Vomero et al 2017) than metal microelectrodes, its effective surface area is lower than conducting polymers and nanocarbon.…”

“…However, although GC electrodes provides a superior electrochemical stability (Nimbalkar et al 2018; Vomero et al 2017) and improved coating adhesion (Castagnola et al 2017; Vomero et al 2017) than metal microelectrodes, its effective surface area is lower than conducting polymers and nanocarbon. Poly(3,4-ethylenedioxythiophene)/acid functionalized carbon nanotube (PEDOT/CNT) is a high surface area electrode coating that has been shown to dramatically reduce impedance, improve electrophysiological recording (Alba et al 2015; Kozai et al 2015) and stimulation (Kolarcik et al 2014; Luo et al 2011; Zheng et al 2022), and enable sensitive detection of tonic dopamine (DA) using SWV (Castagnola et al 2022). In this work, we focused on the development for direct tonic 5-HT measurement using an optimized SWV waveform in combination with PEDOT/CNT coating on GC MEA.…”

“…Several studies suggested that reduced mechanical mismatch between the flexible probe and brain tissue contributes to improved longevity of electrophysiological recording (He et al 2020; Luan et al 2017; Vomero et al 2022; Xie et al 2012; Zhao et al 2019). Using a pattern-transfer technique (Castagnola et al 2022; Castagnola et al 2021b; Vomero et al 2017), in combination with the high-resolution mask-less photolithography process (Castagnola et al 2022), we integrated GC microelectrodes on SU-8 flexible substrate, and examine the acute and chronic 5-HT sensing capability of our flexible PEDOT/CNT-coated GC MEAs microelectrodes, as well as the host tissue response in comparison to stiff counterpart.…”