Surface Fouling of Ultrananocrystalline Diamond Microelectrodes during Dopamine Detection: Improving Lifetime via Electrochemical Cycling An-Yi Chang, Gaurab Dutta, Shabnam Siddiqui, and Prabhu U. Arumugam* Institute for Micromanufacturing, Louisiana Tech University, 911 Hergot Avenue, Ruston, Louisiana 71272, United States * S Supporting Information ABSTRACT: In this work, we report the electrochemical response of a boron-doped ultrananocrystalline diamond (BDUNCD) micro- electrode during long-term dopamine (DA) detection. Specifically, changes to its electrochemical activity and electroactive area due to DA byproducts and surface oxidation are studied via scanning electron microscopy, energy dispersive spectroscopy, electrochemical impedance spectroscopy, and silver deposition imaging (SDI). The fouling studies with amperometry (AM) and fast scan cyclic voltammetry (FSCV) methods suggest that the microelectrodes are heavily fouled due to poor DA−dopamine-o-quinone cyclization rates followed by a combination of polymer formation and major changes in their surface chemistry. SDI data confirms the presence of the insulating polymer with sparsely distributed tiny electroactive regions. This resulted in severely distorted DA signals and a 90% loss in signal starting as early as 3 h for AM and a 56% loss at 6.5 h for FSCV. This underscores the need for cleaning of the fouled microelectrodes if they have to be used long-term. Out of the three in vivo suitable electrochemical cycling cleaning waveforms investigated, the standard waveform (−0.4 V to +1.0 V) provides the best cleaned surface with a fully retained voltammogram shape, no hysteresis, no DA signal loss (a 90 ± 0.72 nA increase), and the smallest charge transfer resistance value of 0.4 ± 0.02 MΩ even after 6.5 h of monitoring. Most importantly, this is the same waveform that is widely used for in vivo detection with carbon fiber microelectrodes. Future work to test these microelectrodes for more than 24 h of DA detection is anticipated. KEYWORDS: Ultrananocrystalline diamond, fouling, electrochemical, cleaning, dopamine, sensitivity ■ INTRODUCTION Chronic monitoring of extracellular neurochemicals is critical to the understanding of several brain disorders. 1,2 Studies have shown that abnormal levels of neurochemicals (e.g., dopamine (DA), serotonin, glutamate, adenosine, γ-aminobutyric acid (GABA)) are linked to Parkinson’s, 3,4 epilepsy, 5,6 Alz- heimer’s, 7−9 and many other brain disorders. Recently, treatment methods such as deep brain stimulation (DBS) have emerged as a successful alternative 10,11 to medications and standard therapeutic interventions. 10−14 Clinical DBS treatment is an iterative process in which stimulation parameters such as stimulus frequency, amplitude, and pulse duration are controlled in an open-loop configuration to regulate neurochemical release. But to maximize benefits and reduce side effects a closed-loop approach that applies neurochemical feedback to guide stimulation parameters is preferred. 15 Electrochemical (EC) techniques such as amperometry (AM) and fast scan cyclic voltammetry (FSCV) are routinely used to directly measure changes in neurochemical levels. 16−18 Such neurochemical measurements are usually performed rapidly with good sensitivity and selectivity with carbon microelectrodes. 19,20 The carbon fiber microelectrode (CFM) with its small size (∼5−10 μm diameter) is the current gold standard electrode for neurochemical sensing. 21,22 When combined with extended-scan FSCV (greater than +1.2 V), detection limits in the nanomolar range are obtained for several important neurochemicals. 23−25 Among the electro- active neurochemicals, DA plays a critical role in the central nervous system. The seminal work of Ralph Adams demonstrated DA detection in vitro and in vivo by electro- chemical methods. 26 For example, FSCV was successfully used to detect DA in the brain of an anesthetized rat selectively. 27 Unfortunately, the DA oxidation on carbon electrodes fouls its surface, which results in a significant reduction of its oxidation current (i.e., detection signal). For example, a 50% fouling was observed at the CFM within 2 h of AM 28 or FSCV detection. 29 A 35% reduction in sensitivity was observed at hydrogenated conical-tip carbon electrodes. 30 Another disadvantage of CFM is its relatively small “faradaic electrochemical potential Received: May 28, 2018 Accepted: October 4, 2018 Published: October 4, 2018 Research Article pubs.acs.org/chemneuro Cite This: ACS Chem. Neurosci. 2019, 10, 313-322 © 2018 American Chemical Society 313 DOI: 10.1021/acschemneuro.8b00257 ACS Chem. Neurosci. 2019, 10, 313−322 Downloaded via UNIV OF NEW HAMPSHIRE on February 11, 2019 at 23:03:06 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.