Pyrolyzed Parylene Electrodes for Detection of Tryptophan, Tyrosine, and Gonadotropin-Releasing Hormone

Sensitive and selective detection of neurochemicals such as neuropeptides is critical for understanding brain signaling. While carbon-fiber microelectrodes (CFMEs) are widely used for these measurements, alternative electrode materials and fabrication techniques could improve sensitivity and versatility. In this study, we investigate pyrolyzed parylene-N microelectrodes (PPNMEs) as a promising platform for making thin-film carbon electrodes for the detection of electroactive amino acids and neuropeptides. We evaluated the performance of PPNMEs for the detection of tryptophan (Trp), tyrosine (Tyr), and the neuropeptide gonadotropin-releasing hormone (GnRH), which contains these electroactive residues. PPNMEs demonstrated significantly greater sensitivity with fast-scan cyclic voltammetry, with signal amplitudes approximately four times higher than those observed with CFMEs. After normalization for surface area, PPNMEs exhibited 3-, 5-, and 2.7-fold higher signals than CFMEs for Trp, Tyr, and GnRH, respectively. Additionally, PPNMEs facilitated faster electron transfer kinetics, as evidenced by reduced oxidation potentials. There were enhanced signals for secondary oxidation peaks at PPNMEs because the rougher surface can trap intermediates near the surface, facilitating detection of downstream electrochemical reactions. Scan rate analysis indicates more adsorption-controlled detection, contributing to improved sensitivity. Importantly, PPNMEs enabled sensitive detection of GnRH in brain tissue slices, including both puffed-on applications and spontaneous endogenous GnRH release in the median eminence. These results highlight the potential of PPNMEs as a new class of carbon-based electrodes, offering a promising alternative to CFMEs for high-sensitivity, low-potential detection of neurochemicals in biological tissues.