Abstract
Electrochemical sensors rely on reference electrodes (REs) to provide stable potential standards, ensuring accurate and reliable detection. The development of biocompatible, stable, and miniaturized REs to replace conventional Ag/AgCl electrodes is crucial for translating electrochemical sensing for human applications. This study evaluates the performance of thin-film electrodes made from gold (Au), platinum (Pt), poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS), and platinum-iridium (Pt-Ir) as REs for fast-scan cyclic voltammetry (FSCV), a widely used technique for real-time neurotransmitter detection. Using dopamine (DA) sensing as a model platform, our results demonstrate that Pt-Ir electrodes provide the necessary stable potential, low drift, and high reproducibility for FSCV sensing, even at a reduced size of 0.1 mm × 0.1 mm. Additionally, Pt-Ir exhibited performance comparable to Ag/AgCl electrodes across various pH levels and in the presence of biofouling agents. These findings highlight Pt-Ir as a promising alternative RE, with strong potential for integration into miniaturized electrochemical sensors for both preclinical and clinical applications.