Capillary electrophoresis for automated on-line monitoring of suspension cultures: Correlating cell density,nutrients and metabolites in near real-time |
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Authors: | Ala A Alhusban Michael C Breadmore Nuri Gueven Rosanne M Guijt |
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Institution: | 1. School of Medicine, Faculty of Health Sciences, University of Tasmania, Australia;2. Australian Center of Research on Separation Science (ACROSS), School of Physical Sciences, Faculty of Science, Engineering and Technology, University of Tasmania, Australia;3. School of Medicine and ACROSS, Faculty of Health Sciences, University of Tasmania, Australia |
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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. |
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Keywords: | Sequential injection capillary electrophoresis Bioprocess monitoring Online monitoring Bioreactor Capillary electrophoresis Suspension cell culture Lactate Glucose Glutamine |
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