RESUMEN
Neurochemical sensing with implantable devices has gained remarkable attention over the last few decades. A promising area of this research is the progress of novel electrodes as electrochemical tools for neurotransmitter detection in the brain. The boron-doped diamond (BDD) electrode is one such candidate that previously has been reported for its excellent electrochemical properties, including a wide working potential, superior chemical inertness and mechanical stability, good biocompatibility and resistance to fouling. Meanwhile, limited research has been conducted on the BDD as a microelectrode for neurochemical detection. Our team has developed a freestanding, all diamond microelectrode consisting of a boron-doped polycrystalline diamond core, encapsulated in an insulating polycrystalline diamond shell, with a cleaved planar tip for electrochemical sensing. This all-diamond electrode is advantageous due to its - (1) batch fabrication using wafer technology that eliminates traditional hand fabrication errors and inconsistencies, (2) absence of metal-based wires, or foundations, to improve biocompatibility and flexibility, and (3) sp 3 carbon surface with resistance to biofouling, i.e. adsorption of proteins or unwanted molecules at the electrode surface in a biological environment that impedes overall electrode performance. Here, we provide findings on further in vitro testing and development of the freestanding boron-doped diamond microelectrode (BDDME) for neurotransmitter detection using fast scan cyclic voltammetry (FSCV). In this report, we elaborate on - 1) an updated fabrication scheme and work flow to generate all diamond BDDMEs, 2) slow scan cyclic voltammetry measurements of reference and target analytes to understand basic electrochemical behavior of the electrode, and 3) FSCV characterization of common neurotransmitters, and overall favorability of serotonin (5-HT) detection. The BDDME showed a 2-fold increased FSCV response for 5-HT in comparison to dopamine (DA), with a limit of detection of 0.16 µM for 5-HT and 0.26 µM for DA. These results are intended to expand on the development of the next generation BDDME and guide future in vivo experiments, adding to the growing body of literature on implantable devices for neurochemical sensing.
RESUMEN
Fast-scan cyclic voltammetry (FSCV) is an electrochemical sensing technique that can be used for neurochemical sensing with high spatiotemporal resolution. Carbon fiber microelectrodes (CFMEs) are traditionally used as FSCV sensors. However, CFMEs are prone to electrochemical fouling caused by oxidative byproducts of repeated serotonin (5-HT) exposure, which makes them less suitable as chronic 5-HT sensors. Our team is developing a boron-doped diamond microelectrode (BDDME) that has previously been shown to be relatively resistant to fouling caused by protein adsorption (biofouling). We sought to determine if this BDDME exhibits resistance to electrochemical fouling, which we explored on electrodes fabricated with either femtosecond laser cutting or physical cleaving. We recorded the oxidation current response after 25 repeated injections of 5-HT in a flow-injection cell and compared the current drop from the first with the last injection. The 5-HT responses were compared with dopamine (DA), a neurochemical that is known to produce minimal fouling oxidative byproducts and has a stable repeated response. Physical cleaving of the BDDME yielded a reduction in fouling due to 5-HT compared with the CFME and the femtosecond laser cut BDDME. However, the femtosecond laser cut BDDME exhibited a large increase in sensitivity over the cleaved BDDME. An extended stability analysis was conducted for all device types following 5-HT fouling tests. This analysis demonstrated an improvement in the long-term stability of boron-doped diamond over CFMEs, as well as a diminishing sensitivity of the laser-cut BDDME over time. This work reports the electrochemical fouling performance of the BDDME when it is repeatedly exposed to DA or 5-HT, which informs the development of a chronic, diamond-based electrochemical sensor for long-term neurotransmitter measurements in vivo.
