Rapid characterization of protein productivity and production stability of CHO cells by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
Article first published online: 18 APR 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Rapid Communications in Mass Spectrometry
Volume 25, Issue 10, pages 1407–1412, 30 May 2011
How to Cite
Feng, H.-t., Sim, L. C., Wan, C., Wong, N. S. C. and Yang, Y. (2011), Rapid characterization of protein productivity and production stability of CHO cells by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom., 25: 1407–1412. doi: 10.1002/rcm.5011
- Issue published online: 18 APR 2011
- Article first published online: 18 APR 2011
- Manuscript Accepted: 11 MAR 2011
- Manuscript Revised: 9 MAR 2011
- Manuscript Received: 26 JAN 2011
The biopharmaceutical industry has been in pursuit of strategies which can isolate stable and high-producing cell lines. The whole cell mass spectrometry method by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) is a rapid and simple method for cell characterization based on the differences in the fingerprints of the mass spectra. This work describes how the method was evaluated for the application of screening for stable and high-producing clones from a panel of recombinant Chinese hamster ovary (CHO) cell lines. Detectable m/z values and their relative intensities were collected and processed by partial least squares (PLS). To reduce the errors introduced by the preparation method and spectra noise, high intensity preliminary data was selected and the number of variables introduced was validated by leave-one-out cross-validation. The differences in recombinant protein productivity and titer were revealed by PLS regression with promising results. Partial least-squares discriminant analysis (PLS-DA) was applied to differentiate stable and unstable cell lines as traditional stability testing would require several months involving numerous continuous passages. Results confirmed that the whole cell MALDI-TOF method can be a powerful method for routine monitoring of bioprocesses and study can be further developed by extending the number of the cell lines tested to establish a recombinant cell line database. Copyright © 2011 John Wiley & Sons, Ltd.