Micropillar array-based microfluidic device for electrochemical monitoring of cell culture health

Abstract

Glucose levels serve as a fundamental indicator of cell health, reflecting crucial aspects of cellular metabolism and energy production. While effective, traditional methods such as spectrophotometry and chromatography have limitations, such as labour-intensive sample collection, reliance on bulky equipment, extensive sample preparation, and prolonged experimental durations. To address these issues, we introduce a micropillar-based microfluidic electrochemical device (MED) for real-time monitoring of glucose levels in diverse cell culture systems, including human induced pluripotent stem cells (hiPSCs) and murine fibroblast cells (GP + E86). This biosensor demonstrates a linear range of 0.025–1.50 mM and a high sensitivity of 4.71 ± 0.13 μA. mM⁻¹, and a low limit of detection of 19.10 ± 0.50 μM. The MED not only delivered fast glucose measurements with accuracy and reliability comparable to ultra-high-performance liquid chromatography (UHPLC) but was also specifically evaluated on GP + E86 murine fibroblast cells at varying seeding densities (1:5 and 1:10 ratios), across different culturing times to accurately monitor dynamic metabolic shifts associated with various growth phases. Furthermore, the MED effectively detected significant changes in glucose consumption in hiPSCs cell cultures contaminated with Escherichia coli (E. coli), highlighting its potential for early contamination detection. Integrating non-invasive, continuous monitoring platforms enhances the reliability of experimental outcomes by enabling cell health monitoring without disrupting the cell culture process. This approach enables real-time monitoring of cell cultures ensuring accurate detection of metabolic changes and early detection of media contamination.