Metal/Insulator/Metal Sandwich Structure Improves Background Potential Stability of Galvanic Redox Potentiometry

Galvanic redox potentiometry (GRP) has been used in various research fields, particularly for <i>in vivo</i> neurotransmitter detection. However, background potential fluctuations significantly limit its application for detecting basal neurotransmitter levels in real samples. Herein, we demonstrate that a metal/insulator/metal sandwich structure substantially improves the GRP background potential stability. For this purpose, a Au/dithiol/Au nanoparticle (NP) sandwich electrode was controllably constructed using a self-assembly technique. Mechanistic studies reveal that background potential fluctuations originate from two key sources: specific anion adsorption at the electrode-electrolyte interface and interference from redox-active species in solution. The sandwich structure effectively suppresses both factors: the dense dithiol monolayer acts as a physical barrier against anion adsorption and redox interference, while the conductive Au NP layer preserves essential electron transfer. Moreover, the negatively charged Au NPs further eliminate specific anionic adsorption and mitigate pH-related background potential fluctuations. More importantly, by precisely controlling the Au NP density within the sandwich structure, tunable GRP performance (e.g., sensitivity) can be achieved. This work advances the field by offering a universal electrode engineering strategy to stabilize background potentials in GRP-based sensing, enabling calibration-free potentiometric analysis in complex samples.