Biological and Mechanical Limitations for Chronic Fast‐Scan Cyclic Voltammetry Sensor Design

Fast scan cyclic voltammetry (FSCV) is a popular approach for real-time neurochemical sensing. Using a carbon-fiber microelectrode (CFME), sensitive neurochemical sensing can be achieved in the acute setting with sub-second resolution for monoamine neurotransmitters. However, to study neuropsychiatric conditions and neurological functions, it is often of interest to perform longitudinal monitoring of neurotransmitters over chronic timepoints. Despite notable successes, there remains substantial room for improvement in chronic neurochemical sensing performance. Electrode fouling and cellular encapsulation that can occur following surgical implantation can lead to diminished sensor performance over time. Additionally, working and reference electrodes can suffer from etching and polarization that can hinder their longevity and stability. Here, we review current challenges facing chronic neurochemical sensors and discuss state-of-the-art advancements in electrode material and device design choices. We cover how the biological environment can negatively affect sensing performance and how device design can mitigate these effects. We also provide examples of state-of-the-art electrode technologies that have been developed to improve chronic neurochemical sensing. Improvements in FSCV as a tool for chronic neurotransmitter sensing will open new opportunities to study neurodegenerative and neuropsychiatric diseases, develop feedback systems for neuromodulation, and explore the neurochemical underpinnings of normal brain function and behavior.