1. Robust on-line sampling and analysis during long-term perfusion cultivation of mammalian cells
- Author
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Mehdi Saghafi, Christoph Knappe, Stefan Steigmiller, Cary Matanguihan, Chetan T. Goudar, and LeeWey Chong
- Subjects
Sample (material) ,Cell Culture Techniques ,Analytical chemistry ,Sampling (statistics) ,Bioengineering ,General Medicine ,Applied Microbiology and Biotechnology ,Bioreactors ,Perfusion Culture ,Robustness (computer science) ,Bioreactor ,Animals ,Environmental science ,Process control ,Sample preparation ,Perfusion ,Biotechnology ,Biomedical engineering - Abstract
In an attempt to support robust automated sampling and analysis of mammalian cell bioreactors, an integrated platform, BaychroMAT®, was developed which includes an innovative sterile sampling device, automated sample transport, a sample preparation module, online analyzers, and communication interfaces to process automation systems. The robustness of this platform was verified by applying it to a laboratory-scale perfusion bioreactor that was operated for over 100 days. Both manual and automated samples were collected over the course of the run and a comparison was made for cell density, viability, glucose, and lactate concentrations. The highest variability (14.4%) was seen for cell density estimates while those for viability, glucose, and lactate were 0.7, 12.9, and 8.2%, respectively. In addition, cell density set-point changes were made towards the end of the perfusion culture and the high frequency automated samples provided a higher resolution description of the dynamics of cell density change compared to less frequent manual sampling. Overall, our results indicate stable and robust operation of the BaychroMAT® platform in a long-term perfusion culture. This success should readily translate to shorter duration fed-batch cultures thereby enabling feed-back control based on real-time nutrient measurements.
- Published
- 2013