title: Robust on-line sampling and analysis during long-term perfusion cultivation of mammalian cells.
abstract: In an attempt to support robust automated sampling and analysis of mammalian cell bioreactors, an integrated platform, BaychroMA®, 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.
authors.affiliation: Bayer Technology Services GmbH, 51368 Leverkusen, Germany.
authors.forename: LeeWey
authors.initials: L
authors.lastname: Chong
authors.forename: Mehdi
authors.initials: M
authors.lastname: Saghafi
authors.forename: Christoph
authors.initials: C
authors.lastname: Knappe
authors.forename: Stefan
authors.initials: S
authors.lastname: Steigmiller
authors.forename: Cary
authors.initials: C
authors.lastname: Matanguihan
authors.forename: Chetan T
authors.initials: CT
authors.lastname: Goudar
mesh_terms: D000818:Animals; D019149:Bioreactors; D001709:Biotechnology; D018929:Cell Culture Techniques / Q000379:methods*