A Silicon-Based Field-Effect Biosensor for Drug-Induced Cardiac Extracellular Calcium Ion Change Detection

Calcium ions participate in the regulation of almost all biological functions of the body, especially in cardiac excitation-contraction coupling, acting as vital signaling through ion channels. Various cardiovascular drugs exert their effects via affecting the ion channels on the cell membrane. The current strategies for calcium ion monitoring are mainly based on fluorescent probes, which are commonly used for intracellular calcium ion detection (calcium imaging) and cannot achieve long-term monitoring. In this work, an all-solid-state silicone-rubber ion-sensitive membrane was fabricated on light-addressable potentiometric sensors to establish a program-controlled field-effect-based ion-sensitive light-addressable potentiometric sensor (LAPS) platform for extracellular calcium ion detection. L-type calcium channels blocker verapamil and calcium channel agonist BayK8644 were chosen to explore the effect of ion channel drugs on extracellular calcium ion concentration in HL-1 cell lines. Simultaneously, microelectrode array (MEA) chips were employed to probe the HL-1 extracellular field potential (EFP) signals. The Ca²⁺ concentration and EFP parameters were studied to comprehensively evaluate the efficacy of cardiovascular drugs. This platform provides more dimensional information on cardiovascular drug efficacy that can be utilized for accurate drug screening.