Abstract: Ion-selective electrodes have been widely used for inorganic ion detection; however, conventional micrometer-tipped electrodes cannot meet the growing demand for calcium imaging with high spatial resolution. Here, we report a sub-100 nm calcium-selective electrode based on a quartz nanopore. A classical calcium ionophore IV membrane cocktail was introduced into a 50 nm laser-pulled quartz conical nanopore by centrifugation, constructing a nanoscale ion-sensing interface. The electrode exhibited a linear potentiometric response of 19.14 mV/dec over the calcium concentration range from 1×10^-7 mol/L to 1×10^-2 mol/L, with a detection limit of approximately 100 nmol/L (the lowest concentration tested), and showed favorable selectivity against Na⁺, Mg²⁺, ascorbic acid, and dopamine. The aperture size significantly influenced the response: when reduced to 20 nm, the response slope decreased to 12.98 mV/dec. To the best of our knowledge, 20 nm represents the smallest aperture reported for quartz-nanopore-based ion-selective electrodes, while the 50 nm aperture still exhibits a sub-Nernstian response, offering a promising tool for ion detection in even smaller nanoscale spaces.

Key words: Nanopore, Ion-selective electrode, Calcium detection, Nanoconfinement