Capillary electrophoresis for automated on-line monitoring of suspension cultures: Correlating cell density, nutrients and metabolites in near real-time.
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.
School of Medicine, Faculty of Health Sciences, University of Tasmania, Australia; Australian Center of Research on Separation Science (ACROSS), School of Physical Sciences, Faculty of Science, Engineering and Technology, University of Tasmania, Australia; School of Medicine and ACROSS, Faculty of Health Sciences, University of Tasmania, Australia.
Ala A
AA
Alhusban
Australian Center of Research on Separation Science (ACROSS), School of Physical Sciences, Faculty of Science, Engineering and Technology, University of Tasmania, Australia.
Michael C
MC
Breadmore
School of Medicine, Faculty of Health Sciences, University of Tasmania, Australia.
Nuri
N
Gueven
School of Medicine, Faculty of Health Sciences, University of Tasmania, Australia; School of Medicine and ACROSS, Faculty of Health Sciences, University of Tasmania, Australia. Electronic address: Rosanne.Guijt@utas.edu.au.
Rosanne M
RM
Guijt
D019149:Bioreactors; D002452:Cell Count / Q000379:methods*; D018929:Cell Culture Techniques / Q000379:methods*; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism; D019075:Electrophoresis, Capillary / Q000379:methods*; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D005973:Glutamine / Q000032:analysis / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D019344:Lactic Acid / Q000032:analysis / Q000378:metabolism
D003470:Culture Media; D005973:Glutamine; D019344:Lactic Acid; D005947:Glucose
Bioprocess monitoring; Bioreactor; Capillary electrophoresis; Glucose; Glutamine; Lactate; Online monitoring; Sequential injection capillary electrophoresis; Suspension cell culture