Capillary electrophoresis for automated on-line monitoring of suspension cultures: Correlating cell density, nutrients and metabolites in near real-time

Abstract

Increasingly stringent demands on the production of biopharmaceuticals demand monitoring of process parameters that impact on their quality. We developed an automated platform for on-line, near real-time monitoring of suspension cultures by integrating microfluidic components for cell counting and filtration with a high-resolution separation technique. This enabled the correlation of the growth of a human lymphocyte cell line with changes in the essential metabolic markers, glucose, glutamine, leucine/isoleucine and lactate, determined by Sequential Injection-Capillary Electrophoresis (SI-CE). Using 8.1 mL of media (41 μL per run), the metabolic status and cell density were recorded every 30 min over 4 days. The presented platform is flexible, simple and automated and allows for fast, robust and sensitive analysis with low sample consumption and high sample throughput. It is compatible with up- and out-scaling, and as such provides a promising new solution to meet the future demands in process monitoring in the biopharmaceutical industry.