The Ca²⁺-FET device detects Ca²⁺ concentrations associated with MDA-MB-231 cell activities, such as proliferation, apoptosis, and Ca²⁺ fluctuation. The technique demonstrates the implementation of the ISFET for label-free and real-time ion monitoring, which benefits cancer research and therapeutic applications.

Abstract

Transfer of extracellular and intracellular calcium ions (Ca²⁺) plays a crucial role in programmed cell death, with varied Ca²⁺ concentrations associated with cell growth, proliferation, apoptosis, and so on. Real-time monitoring of extracellular Ca²⁺ concentrations ([Ca²⁺]_e) can provide valuable quantitative insights into programmed cell death, which may greatly benefit cancer therapy and other biological applications. This study used a modified ion-sensitive field-effect transistor (ISFET) as a platform for Ca²⁺ sensing. The ISFET device was functionalized with a Ca²⁺-selective membrane containing polyurethane (PU) and calcium ionophore II. The Ca²⁺-FET device exhibited a sensitivity of 35 ± 3 mV/pCa (pCa 0–5) toward Ca²⁺ with insignificant cross-sensitivity to other ions, such as sodium (Na⁺) and potassium (K⁺). The device was applied to monitor [Ca²⁺]_e concentrations in the MDA-MB-231 breast cancer cell culture, showing sufficient reliance in detecting Ca²⁺ concentrations (0.1 mM to 1 M (pCa 0–5)) correlated with cellular activities. This technique offers a noninvasive and label-free approach for real-time Ca²⁺ monitoring in cell culture, with potential applications in cancer research and therapeutic development.