Calcium Ion Sensors with Unrivaled Stability and Selectivity Using a Bilayer Approach with Ionically Imprinted Nanocomposites

Calcium ion sensors are essential in clinical diagnosis, particularly in the management of chronic kidney disease. Multiple approaches have been developed to measure calcium ions, including flame photometry and ion chromatography. However, these devices are bulky and require specialized staff for operation and evaluation. The integration of all-solid-state ion-selective determination allows the design of miniaturized and low-cost sensing that can be used for the continuous monitoring of electrolytes. However, clinical use has been limited due to the low electrochemical stability and selectivity and high noise rate. This manuscript reports for the first time a novel miniaturized Ca²⁺ ion-selective sensor, developed by using a two-layer nanocomposite thin film (5 µm thick). The device consists of functionalized silica nanoparticles embedded in a poly(vinyl chloride) (PVC) film, which was deposited onto a nanoporous zirconium silicate nanoparticle layer that served as the sensing surface. Systematic evaluation revealed that perfluoroalkane-functionalized silica nanoparticles enhanced Ca²⁺ selectivity by minimizing K⁺ diffusion, confirmed by both potentiometric measurements and quartz microbalance studies. The final sensor demonstrated a super-Nernstian sensitivity of 37 mV/Log[Ca²⁺], a low signal drift of 28 µV/s, a limit of detection of 1 µM, and exceptional selectivity against Na⁺, K⁺, and Mg²⁺ ions. Long-term testing showed stable performance over three months of continuous operation. Clinical testing was conducted on patients with chronic kidney disease. An accurate real-time monitoring of electrolyte dynamics in dialysate samples was observed, where final concentrations matched those observed in physiological conditions.