3D-Printed Potentiometric Multicells for Enhanced Analytical Performance of Solid Contact Ion-Selective Electrodes

The sensitivity of ion-selective electrodes (ISEs) that are operated by equilibrium potentiometry is determined by the well-known Nernst equation. An elegant concept that involved connecting various potentiometric cells in series was demonstrated in early reports with the aim of increasing the sensitivity of ISEs by multiplying the theoretical slope by the number of cells used. In the 1980s and 1990s, the concept of cells connected in series (CCS) was demonstrated to be capable of amplifying the potentiometric signal, enhancing the determination of selected analytes. Nevertheless, the use of bulky electrodes and cumbersome methods for sensor fabrication restricted its applicability to modern analytical contexts. Hereby, we revive and modernize this overlooked concept by introducing 3D-printed potentiometric multicells (3DP-PMCs) that integrate solid-contact ISEs and solid-state reference electrodes into compact, interconnected architectures. Owing to the design flexibility and reproducibility of 3D printing, the 3DP-PMC platform enables slope multiplication by up to 8-fold, achieving sensitivities of 475 ± 12 mV dec^-1. Importantly, this enhanced performance is maintained across narrow concentration intervals, with the octuple-cell configuration allowing detection of 0.1 mM concentration changes (equivalent to a 2% change) not achievable with an individual cell configuration. This work demonstrates, for the first time, the practical translation of the CCS principle into a miniaturized, modular, and easily manufacturable format, paving the way for its integration into microfluidic, wearable, and point-of-care devices.