CMOS-Based Implantable Multi-Ion Image Sensor for Mg²⁺ Measurement in the Brain

An implantable multi-ion image sensor equipped with magnesium ion (Mg²⁺)-and calcium ion (Ca²⁺)-sensitive membranes was fabricated for the selective measurement of extracellular Mg²⁺ in the brain, and the sensor performance was evaluated. This sensor complements the low selectivity of the Mg²⁺-sensitive membrane for Ca²⁺ by depositing a Ca²⁺-sensitive membrane in addition to the Mg²⁺-sensitive membrane on a CMOS (Complementary Metal Oxide Semiconductor)-based potentiometric sensor array with 5.65 × 4.39 µm² pitch, enabling selective measurement of Mg²⁺ and Ca²⁺. Characterization of the sensor confirmed a Ca²⁺ sensitivity of 26.5 mV/dec and Mg²⁺ sensitivity of 19 mV/dec. Based on validation experiments with varying concentrations of Mg²⁺ and Ca²⁺, selective Ca²⁺ and Mg²⁺ measurements were successfully achieved. Furthermore, real-time imaging of Mg²⁺ and Ca²⁺ and quantification of their concentration changes were performed. The developed sensor may be successfully applied for extracellular multi-ion imaging of Mg²⁺ and Ca²⁺ in the living brain.