Utilizing Cole-Cole parameters for in-line feedback: Cell culture process adjustments based on cell health

In the biopharmaceutical industry, effective process control strategies are essential for enhancing drug substance quality and yield. This study presents dielectric spectroscopy as a novel approach for in-line monitoring of cell apoptosis, enabling earlier detection of apoptotic events and related cellular changes. Utilizing permittivity measurements, we assessed Cole-Cole parameters, specifically critical frequency (f_c) and delta epsilon (Δε), as key performance indicators (KPIs) for real-time monitoring of cell health in CHO cell cultures during batch and perfusion processes. Our findings demonstrate that variations in these parameters correlate with cellular stress responses, such as nutrient limitation and high shear conditions, providing timely signals for process monitoring and control. By integrating these in-line measurements, we can enhance feeding strategies, ultimately improving cell viability and productivity. This approach not only streamlines the monitoring process but also offers a robust framework for proactive adjustments in bioprocessing, thereby optimizing overall performance and resource utilization.