Parallel comparison of in situ Raman and NIR spectroscopies to simultaneously measure multiple variables toward real-time monitoring of CHO cell bioreactor cultures

For the first time, the ability of in situ Raman and Near Infrared (NIR) spectroscopies to predict in real-time the concentration of viable Chinese Hamster Ovary (CHO) cells, glucose, lactate, glutamine, ammonium and antibodies in bioreactors has been compared in parallel. PLS models were developed using Raman and NIR spectra recorded at same time points and in same cultures. Multivariate figures of merit were established to thoroughly compare the performances of models. Raman spectroscopy was found to better predict concentrations of glucose, lactate and antibody, while NIR spectroscopy predicted better glutamine and ammonium ion concentrations. By applying the models developed on spectra recorded continuously during a batch culture, both spectroscopies were able to monitor simultaneously the general trends of the concentration of different analytes, while Raman predictions were more accurate at the beginning of the culture. Moreover, other chemometric methods (partial least square regression of type 2 and spectral combination) were tested, but leading to only limited model performance improvements. Both spectroscopies are suitable tools for real-time monitoring of cell culture bioprocesses, while Raman spectroscopy provides several advantages concerning sensibility, selectivity and limit of detection. These results provide useful information for academic researchers and pharmaceutical industries to choose the most adequate spectroscopic technology for their cell culture bioprocesses.