Development of Microfluidic Organ-on-a-Chip Systems Dedicated to the Analysis of Cell Morphology

Traditional medical techniques are constrained by macro-scale detection methods, making it difficult to capture dynamic changes at the cellular level. The miniaturization and high-throughput capabilities of integrated circuit technology enable precise manipulation and real-time monitoring of biological processes. In this study, COMSOL Multiphysics 6.3 software was used to model electrode units, simulating the interaction between cells and their biological environment. From the perspective of electrode arrays, the influence of varying electrode-cell contact areas on electrical signals was investigated, and the structure and layout of the microelectrode array (MEA) were optimized. The research explored the relationship between cellular activity and electrical properties, as well as the effect of cellular activity on membrane permeability. Simulation results demonstrated that larger electrode coverage areas improve potential distribution. The intact phospholipid bilayer and functional membrane proteins of living cells create a significant current-blocking effect, with impedance values reaching 105–106 Ω·cm2. In contrast, apoptotic or necrotic cells exhibit structural damage and ion channel inactivation, leading to significantly enhanced membrane permeability, with impedance decreasing by 1–2 orders of magnitude. Further simulations involved modeling microfluidic channels to study cellular behavior within them. Frequency response analysis and Bode plots revealed that impedance differences between low and high frequencies could distinguish living cells (higher impedance) from apoptotic cells (lower impedance). Therefore, Bode plot analysis can assess membrane permeability and infer cellular health or apoptotic state. Additionally, this study examined micro-nanofabrication techniques, particularly the lift-off process for microelectrode fabrication, and optimized photoresist selection in photolithography.