fulltext.study @t Gmail

Mammalian cell culture scale-up and fed-batch control using automated flow cytometry

Paper ID Volume ID Publish Year Pages File Format Full-Text
24825 43539 2008 7 PDF Available
Title
Mammalian cell culture scale-up and fed-batch control using automated flow cytometry
Abstract

Detailed knowledge of mammalian cell culture proliferation kinetics is important to determine fed-batch strategies for industrial bioreactor operations. In particular, predicting the end of exponential proliferation in batch culture is a critical process parameter during culture scale-up. Using automated flow cytometry we show that an increase in the non-viable sub-population in CHO cell culture can predict the onset of stationary phase by approximately 40 h. This enables a completely automated culture scale-up process as well as a reliable and reproducible control of fed-batch additions during culture expansion. It is shown that the automated scale-up results in a significantly higher total cell count in the reactor than manual scale up initiated in stationary growth phase. During individual, subsequent culture expansions, a significant variation in the proliferation rate was observed despite control of bulk culture parameters. Thus, automated flow cytometry is critical to uncovering useful process parameters that enable new control strategies. Such improved process supervision derived from knowledge-based data analysis is central to the FDA's Process Analytical Technology (PAT) initiative and is expected to result in better and higher quality products.

Keywords
Automated flow cytometry; Bioreactor monitoring; Mammalian cell culture; Single-cell heterogeneity; Process Analytical Technology; PAT initiative
First Page Preview
Mammalian cell culture scale-up and fed-batch control using automated flow cytometry
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 135, Issue 2, 1 June 2008, Pages 174–180
Authors
, ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering