Electrochemical detection of amine neurotransmitters is drastically different in buffer solutions, in vivo, and cell culture systems

Detection of neurotransmitters requires high sensitivity and temporal resolution, favoring electrochemical techniques for the sensing mechanism. However, electrochemical detection of amine neurotransmitters is highly dependent on electrode surface condition and thus, results obtained in clean buffer solutions are not directly applicable to the real measurement environment in vivo or in vitro. In these more complex electrolyte solutions, the presence of antioxidants and surface-adsorbing molecules drastically alters the redox characteristics of amine neurotransmitters, their precursors and metabolites. Accordingly, we surveyed their redox characteristics in the phosphate buffered saline (PBS), cerebrospinal fluid (CSF) and cell culture medium, with high-sensitivity electrodes made of single-walled carbon nanotube network.

The concentration of surface-fouling molecules was lowest in the PBS and highest in the culture medium. Accordingly, electrochemical reaction kinetics were facile in the PBS and sluggish in the culture medium. Surprisingly, analyte molecular structure had much more importance in the CSF compared to other electrolytes, however the reaction kinetics remained to be generally slower in the CSF compared to when measured in the PBS.

Whereas the CSF also contains L-Ascorbic acid and uric acid that are electrochemically active interfering molecules, they are either completely absent or can be omitted in the in vitro setting. On the contrast, the culture medium contains substantially higher concentration of surface-adsorbing molecules that causes more significant fouling of electrode and thus loss of sensitivity. As the in vitro brain-on-a-chip applications are rapidly being adopted, direct comparison of these different experimental settings was essential to understand their implications for electrochemical sensors.