Fast-scan cyclic voltammetry (FSCV) is used with carbon-fiber microelectrodes for the real-time detection of neurotransmitters on the subsecond time scale. With FSCV, the potential is ramped up from a holding potential to a switching potential and back, usually at a 400 V s⁻¹ scan rate and a frequency of 10 Hz. The plot of current vs. applied potential, the cyclic voltammogram (CV), has a very different shape for FSCV than for traditional cyclic voltammetry collected at scan rates which are 1000-fold slower. Here, we explore the theory of FSCV, with a focus on dopamine detection. First, we examine the shape of the CVs. Background currents, which are 100-fold higher than faradaic currents, are subtracted out. Peak separation is primarily due to slow electron transfer kinetics, while the symmetrical peak shape is due to exhaustive electrolysis of all the adsorbed neurotransmitters. Second, we explain the origins of the dopamine waveform, and the factors that limit the holding potential (oxygen reduction), switching potential (water oxidation), scan rate (electrode instability), and repetition rate (adsorption). Third, we discuss data analysis, from data visualization with color plots, to the automated algorithms like principal components regression that distinguish dopamine from pH changes. Finally, newer applications are discussed, including optimization of waveforms for analyte selectivity, carbon nanomaterial electrodes that trap dopamine, and basal level measurements that facilitate neurotransmitter measurements on a longer time scale. FSCV theory is complex, but understanding it enables better development of new techniques to monitor neurotransmitters in vivo.

The carbon-fiber microelectrode has been used for decades as a neurotransmitter sensor. Recently, new strategies have been developed for making carbon electrodes, including using carbon nanomaterials or pyrolyzing a photoresist etched by nanolithography or 3D printing. This review summarizes how chemical and 3D surface structures of new carbon electrodes are optimized for neurotransmitter detection. There are effects of the chemical structure that are advantageous, and nanomaterials are used ranging from carbon nanotubes (CNTs) to graphene to nanodiamond. Functionalization of these materials promotes surface oxide groups that adsorb dopamine, and dopants introduce defect sites good for electron transfer. Polymer coatings such as poly(3,4-ethylenedioxythiophene) (PEDOT) or Nafion also enhance the selectivity, particularly for dopamine over ascorbic acid. Changing the 3D surface structure of an electrode increases the current by adding more surface area. If the surface structure has roughness or pores on the micron scale, the electrode also acts as a thin layer cell, momentarily trapping the analyte for redox cycling. Vertically aligned CNTs as well as lithographically made or 3D printed pillar arrays act as thin layer cells, producing more reversible cyclic voltammograms. A better understanding of how the chemical and surface structure affects the electrochemistry enables rational design of electrodes. New carbon electrodes are being tested in vivo and strategies to reduce biofouling are being developed. Future studies should test the robustness for long term implantation, explore electrochemical properties of neurotransmitters beyond dopamine, and combine optimized chemical and physical structures for real-time monitoring of neurotransmitters.