The mechanisms that control extracellular serotonin levels in vivo are not well-defined. This shortcoming makes it very challenging to diagnose and treat the many psychiatric disorders in which serotonin is implicated. Fast-scan cyclic voltammetry (FSCV) can measure rapid serotonin release and reuptake events but cannot report critically important ambient serotonin levels. In this Article, we use fast-scan controlled adsorption voltammetry (FSCAV), to measure serotonin’s steady-state, extracellular chemistry. We characterize the “Jackson” voltammetric waveform for FSCAV and show highly stable, selective, and sensitive ambient serotonin measurements in vitro. In vivo, we report basal serotonin levels in the CA2 region of the hippocampus as 64.9 ± 2.3 nM (n = 15 mice, weighted average ± standard error). We electrochemically and pharmacologically verify the selectivity of the serotonin signal. Finally, we develop a statistical model that incorporates the uncertainty in in vivo measurements, in addition to electrode variability, to more critically analyze the time course of pharmacological data. Our novel method is a uniquely powerful analysis tool that can provide deeper insights into the mechanisms that control serotonin’s extracellular levels.

Rapid, selective detection of metals in complex samples remains an elusive goal that could provide critical analytical information for biological and environmental sciences and industrial waste management. Fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFMs) is an emerging technique for metal analysis with broad potential applicability because of its rapid response to changes in analyte concentration and minimal disturbance to the analysis medium. In this communication, we report the first effective application of covalently modified CFMs to achieve highly selective, subsecond Cu(II) measurements using FSCV. A two-part strategy is employed for maximum selectivity: Cu(II) binding is augmented by a covalently grafted ionophore, while binding of other metals is prevented by chemical blocking of nonselective surface adsorption sites. The resulting electrodes selectively detect Cu(II) in a complex medium comprising several interfering metals. Overall, this strategy represents a transformative innovation in real-time electrochemical detection of metal analytes.

Aqueous metal behavior is strongly regulated by speciation, which in turn is highly dependent on complexation. Trace metal complexation is difficult to characterize in dynamically changing systems due to a lack of analytical methods that can rapidly report free-metal concentrations. In this paper, we perform proof-of-principle experiments that demonstrate the utility of fast-scan cyclic voltammetry (FSCV) for providing speciation information in real-time by characterizing dynamic Cu(II) binding. We study Cu(II) FSCV responses in 3-(N-morpholino)propanesulfonic acid (MOPS) buffer and characterize the hydrodynamic aspects of our experimental setup (continuously stirred tank reactor). We observe Cu(II) complexation in real-time using five ligands with differing formation constants of Cu(II) complexation. Finally, we utilize geochemical models to fit our real-time experimental Cu(II)-binding curves. Our proof-of-principle experiments show that FSCV is a powerful tool for studying real-time Cu(II) complexation, which is essential speciation information for better interpretation of Cu(II) behavior in dynamically changing systems, such as those encountered in biology or the environment.