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Title: Detection of phase shifts in batch fermentation via statistical analysis of the online measurements: A case study with rifamycin B fermentation
Authors: Doan, X.-T.
Srinivasan, R. 
Bapat, P.M.
Wangikar, P.P.
Keywords: Amycolatopsis mediterranei
Complex medium
Multivariate statistical analysis
Issue Date: 31-Oct-2007
Citation: Doan, X.-T., Srinivasan, R., Bapat, P.M., Wangikar, P.P. (2007-10-31). Detection of phase shifts in batch fermentation via statistical analysis of the online measurements: A case study with rifamycin B fermentation. Journal of Biotechnology 132 (2) : 156-166. ScholarBank@NUS Repository.
Abstract: Industrial production of antibiotics, biopharmaceuticals and enzymes is typically carried out via a batch or fed-batch fermentation process. These processes go through various phases based on sequential substrate uptake, growth and product formation, which require monitoring due to the potential batch-to-batch variability. The phase shifts can be identified directly by measuring the concentrations of substrates and products or by morphological examinations under microscope. However, such measurements are cumbersome to obtain. We present a method to identify phase transitions in batch fermentation using readily available online measurements. Our approach is based on Dynamic Principal Component Analysis (DPCA), a multivariate statistical approach that can model the dynamics of non-stationary processes. Phase-transitions in fermentation produce distinct patterns in the DPCA scores, which can be identified as singular points. We illustrate the application of the method to detect transitions such as the onset of exponential growth phase, substrate exhaustion and substrate switching for rifamycin B fermentation batches. Further, we analyze the loading vectors of DPCA model to illustrate the mechanism by which the statistical model accounts for process dynamics. The approach can be readily applied to other industrially important processes and may have implications in online monitoring of fermentation batches in a production facility. © 2007 Elsevier B.V. All rights reserved.
Source Title: Journal of Biotechnology
ISSN: 01681656
DOI: 10.1016/j.jbiotec.2007.06.013
Appears in Collections:Staff Publications

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