Glucose monitoring and adaptive feeding of mammalian cell culture in the presence of strong autofluorescence by near infrared Raman spectroscopy

Raman spectroscopy offers an attractive platform for real-time monitoring and control of metabolites and feeds in cell culture processes, including mammalian cell culture for biopharmaceutical production. However, specific cell culture processes may generate substantial concentrations of chemical species and byproducts with high levels of autofluorescence when excited with the standard 785 nm wavelength. Shifting excitation further toward the near-infrared allows reduction or elimination of process autofluorescence. We demonstrate such a reduction in a highly autofluorescent mammalian cell culture process. Using the Kaiser RXN2-1000 platform, which utilizes excitation at 993 nm, we developed multivariate glucose models in a cell culture process which was previously impossible using 785 nm excitation. Additionally, the glucose level in the production bioreactor was controlled entirely by Raman adaptive feeding, allowing for maintenance of glucose levels at an arbitrary set point for the duration of the culture. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1574-1580, 2018.