Real time monitoring of bioreactor mAb IgG3 cell culture process dynamics via Fourier transform infrared spectroscopy: Implications for enabling cell culture process analytical technology Academic Article uri icon


  • 2015, Higher Education Press and Springer-Verlag Berlin Heidelberg. Compared to small molecule process analytical technology (PAT) applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufacturing biotechnology drug products. However, the use of inline Fourier transform infrared (FTIR) spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites (including glucose, glutamine, lactate, and ammonia) and protein yield at increasing levels of complexity (simple binary system, fully formulated media, actual bioreactor cell culture process) was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares (PLS) calibration models were established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2nd derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of real time monitoring of the bioreactor cell culture process via FTIR spectroscopy. Its implications for enabling cell culture PAT were discussed.[Figure not available: see fulltext.]

published proceedings

  • Frontiers of Chemical Science and Engineering

author list (cited authors)

  • Wu, H., Read, E., White, M., Chavez, B., Brorson, K., Agarabi, C., & Khan, M.

citation count

  • 15

complete list of authors

  • Wu, Huiquan||Read, Erik||White, Maury||Chavez, Brittany||Brorson, Kurt||Agarabi, Cyrus||Khan, Mansoor

publication date

  • September 2015