Plasma-treated gold microelectrodes for subsecond detection of Zn(II) with fast-scan cyclic voltammetry.

The sensitivity of zinc (Zn(II)) detection using fast-scan cyclic voltammetry (FSCV) with carbon fiber microelectrodes (CFMEs) is low compared to other neurochemicals. We have shown previously that Zn(II) plates to the surface of CFME's and we speculate that it is because of the abundance of oxide functionality on the surface. Plating reduces sensitivity over time and causes significant disruption to detection stability. This limited sensitivity and stability hinders Zn(II) detection, especially in complex matrices like the brain. To address this, we developed plasma-treated gold fiber microelectrodes (AuMEs) which enable sensitive and stable Zn(II) detection with FSCV. Typically, gold fibers are treated using corrosive acids to clean the surface and this step is important for preparing the surface for electrochemistry. Likewise, because FSCV is an adsorption-based technique, it is also important for Zn(II) to adsorb and desorb to prevent irreversible plating. Because of these requirements, careful optimization of the electrode surface was necessary to render the surface for Zn(II) adsorption yet strike a balance between attraction to the surface vs. irreversible interactions. In this study, we employed oxygen plasma treatment to activate the gold fiber surface without inducing significant morphological changes. This treatment effectively removes the organic layer while functionalizing the surface with oxygen, enabling Zn(II) detection that is not possible on untreated gold surfaces. Our results demonstrate significantly improved Zn(II) detection sensitivity and stability on AuME compared to CFME's. Overall, this work provides an advance in our understanding of Zn(II) electrochemistry and a new tool for improved metallotransmitter detection in the brain.

Subsecond Codetection of Dopamine and Estradiol at a Modified Sharkfin Waveform.

17ß-Estradiol (E2) is a ubiquitously expressed hormone that is active in a wide range of neuroprotective and regenerative roles throughout the brain. In particular, it is a well-known dopamine (DA) regulator and is responsible for modulating the expression of dopaminergic receptors and transporters. Recent studies point to E2 release occurring on a rapid time scale and having impacts on DA activity within seconds to minutes. As such, tools capable of monitoring the release of both E2 and DA in real time are essential for developing an accurate understanding of their interactive roles in neurotransmission and regulation. Currently, no analytical techniques capable of codetection of both analytes with high sensitivity, spatiotemporal resolution, extended monitoring, and minimal tissue damage exist. We describe a modified waveform using fast-scan cyclic voltammetry that is capable of low nanomolar detection of both DA and E2 on a subsecond time scale. Both analytes have limits of detection at or below 30 nM and high sensitivity: 11.31 ± 0.55 nA/µM for DA and 9.47 ± 0.36 nA/µM for E2. The waveform is validated in a tissue matrix, confirming its viability for measurement in a biologically relevant setting. This is the first method capable of codetection of fluctuations in DA and E2 with the temporal, spatial, and sensitivity requirements necessary for studying real-time neurochemical signaling.

Dynamic and Rapid Detection of Guanosine during Ischemia.

Guanosine acts in both neuroprotective and neurosignaling pathways in the central nervous system; in this paper, we present the first fast voltammetric measurements of endogenous guanosine release during pre- and post-ischemic conditions. We discuss the metric of our measurements via analysis of event concentration, duration, and interevent time of rapid guanosine release. We observe changes across all three metrics from our normoxic to ischemic conditions. Pharmacological studies were performed to confirm that guanosine release is a calcium-dependent process and that the signaling observed is purinergic. Finally, we show the validity of our ischemic model via staining and fluorescent imaging. Overall, this paper sets the tone for rapid monitoring of guanosine and provides a platform to investigate the extent to which guanosine accumulates at the site of brain injury, i.e., ischemia.

Graphene-Fiber Microelectrodes for Ultrasensitive Neurochemical Detection.

Here, we have synthesized and characterized graphene-fiber microelectrodes (GFME's) for subsecond detection of neurochemicals with fast-scan cyclic voltammetry (FSCV) for the first time. GFME's exhibited extraordinary properties including faster electron transfer kinetics, significantly improved sensitivity, and ease of tunability that we anticipate will have major impacts on neurochemical detection for years to come. GF's have been used in the literature for various applications; however, scaling their size down to microelectrodes and implementing them as neurochemical microsensors is significantly less developed. The GF's developed in this paper were on average 20-30 µm in diameter and both graphene oxide (GO) and reduced graphene oxide (rGO) fibers were characterized with FSCV. Neat GF's were synthesized using a one-step dimension-confined hydrothermal strategy. FSCV detection has traditionally used carbon-fiber microelectrodes (CFME's) and more recently carbon nanotube fiber electrodes; however, uniform functionalization and direct control of the 3D surface structure of these materials remain limited. The expansion to GFME's will certainly open new avenues for fine-tuning the electrode surface for specific electrochemical detection. When comparing to traditional CFME's, our GFME's exhibited significant increases in electron transfer, redox cycling, fouling resistance, higher sensitivity, and frequency independent behavior which demonstrates their incredible utility as biological sensors.