Conference Contribution Details
Mandatory Fields
A. G. Ryder
SciX 2013
Raman spectroscopy in biopharmaceutical manufacturing.
Milwaukee, WI, USA
Invited Lecture
Optional Fields
29-SEP-13
04-OCT-13
Cell culture media (CCM) are an intrinsically vital element in cell culture and the quality of the media is fundamental to the effective growth of healthy cells.  In an industrial context the quality and reproducibility of the CCM determines process productivity and as such it has gained enormous importance with the growth in biological active pharmaceutical ingredients.  CCM are nearly always complex (or very complex) mixtures of materials which span a wide range of concentrations from the ppm level up to 10-20% w/w.  The analytical challenge is thus to develop rapid and cost-effective methods for both qualitative and quantitative assessment of CCM quality in terms of variance and stability.  This has to be implemented for both the solid state and when produced as dilute aqueous solutions ready for use.  Standard chromatographic based methods are generally too slow and time-consuming for rapid screening of these complex mixtures.  Vibrational spectroscopy like Raman and NIR are very useful in this context because they offer rapid, non-contact, non-destructive methods of analysis, that in case of the Raman also offers a high chemical specificity.  However, CCM materials pose some interesting challenges in terms of compositional complexity (e.g. biogenically derived CCM like yeast extracts), fluorescence interference, and strong water signals.  These issues coupled with the need for quantification require the use of extensive chemometric data analysis and careful experimental design.  We show how we applied both 785  and 993 nm based Raman systems to the analysis of these complex materials, and how these can be implemented in an industrial context.  Finally we demonstrate how Surface Enhanced Raman Scattering (SERS) spectroscopy could be utilized for the assessment of CCM changes induced by various environmental factors [3,4].  SERS can show very subtle changes in CCM composition which otherwise are not observable by conventional Raman spectroscopy or by fluorescence spectroscopy [5].   References: 1) A.G. Ryder, J. De Vencentis, B. Li, et al.  J. Raman Spectrosc., 41, 1266, (2010).2) B. Li, P.W. Ryan, B.H. Ray, K.J. Leister, N.M.S. Sirimuthu, A.G. Ryder.  Biotechnol.Bioeng.,107, 290, (2010).3) B. Li, N.M.S. Sirimuthu, B. Ray, A.G. Ryder, J. Raman Spectrosc., 43, 1074, (2012).4) A. Calvet, A.G. Ryder, in preparation.5) A. Calvet, B. Li, A.G. Ryder, submitted.  
Industrial funding
Publication Themes