Critical bioprocess values, metabolites, and other key components can be identified and quantified using in situ, real-time spectroscopic analysis. In cell culture these include monitoring of glucose, lactate, glutamine, glutamate, titre, viable cell density and total cell density. During fermentation, glucose, glycerol ,ethanol, viable cell density, total cell density and other process conditions may be monitored.
Raman spectroscopy is the most useful technique here as water has a very weak Raman signal leaving the information from the medium and cells free of interference.
Raman can be used either non-invasively or with autoclaveable or disposable immersion probes with fittings for most commercially available bioreactors. Recent developments in picosecond Raman show promise for separating the spectra of cells and media, yielding further information.
Raman is also a powerful tool for monitoring and controlling downstream protein purification - read the white paper here
Raman Imaging offers a solution for monitoring the quality and performance of culture media – complex powder mixtures may be analysed by imaging one particle at a time, building up a picture of the mixture and identifying and quantifying the individual components
NIR may also be used for bioprocess monitoring and other unit operations. Nutrients, metabolites and by-products can also be measured in real-time. Because water has a strong NIR signal, the technique is very useful for measuring residual moisture in processes such as lyophilisation.
FTIR with an ATR immersion probe also measures all the components in solution. Clairet can supply complete systems and demountable, sterilisable ATR probes.
UV-Visible can be used for downstream applications such as prediction of protein concentrations in operations such as filling.
Applications Notes:
06 Alcohol Fermentation monitored by Raman
29 Analysis of Mammalian cell culture
63 FT-NIR spectroscopy for biopharmaceutical application
72 Culture media analysis.
