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Raman spectroscopy as a method to replace off‐line pH during mammalian cell culture processes
Author(s) -
Rafferty Carl,
O'Mahony Jim,
Burgoyne Barbara,
Rea Rosemary,
Balss Karin M.,
Latshaw David C.
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27197
Subject(s) - raman spectroscopy , partial least squares regression , robustness (evolution) , biological system , chemistry , analytical chemistry (journal) , process analytical technology , computer science , chromatography , chemical engineering , biochemistry , machine learning , optics , biology , engineering , physics , bioprocess , gene
Raman spectroscopy is a robust, well‐established tool utilized for measuring important cell culture process variables for example, feed, metabolites, and biomass in real‐time. This study further expands the functionality of in‐line Raman spectroscopy coupled with partial least squares (PLS) regression modelling to develop a pH measurement tool. Cell line specific models were developed to enhance the robustness for processes with different pH setpoints, deadbands, and cellular metabolism. The modelling strategy further improved robustness by reducing the temporal complexity of pH shifts by splitting data sets into two time zones reflective of major changes in pH. In addition, models were developed to assess if lactate and partial pressure of carbon dioxide ( p CO 2 ) could be used in a PLS model for pH. Splitting the data sets into early and late for the process resulted in errors of 0.035 pH and 0.034 pH for the two respective Raman cell lines models which was within acceptance criteria. The lactate and p CO 2 PLS model with values provided by Raman models had a further 0.001 pH error reduction. This study illustrates the potential to eliminate off‐line samples to correct for in‐line measurements of pH and further illustrates the capabilities of Raman to measure additional process variables.