Cell Culture Tracking by Multivariate Analysis of Raw LCMS Data François-Thomas Michaud & Pierre Claver Havugimana & Carl Duchesne & François Sanschagrin & Alice Bernier & Roger C. Lévesque & Alain Garnier Received: 12 September 2011 / Accepted: 28 March 2012 / Published online: 5 May 2012 # Springer Science+Business Media, LLC 2012 Abstract Liquid chromatography mass spectrometry (LCMS) is a powerful technique that could serve to rapidly characterize cell culture protein expression profile and be used as a process monitoring and control tool. However, this application is often hampered by both the sample proteome and the LCMS signal complexities as well as the variability of this signal. To alleviate this problem, culture samples are usually extensively fractionated and pretreated before being analyzed by top-end instruments. Such an approach precludes LCMS usage for routine on-line or at-line application. In this work, by applying multivariate analysis (MA) directly on raw LCMS signals, we were able to extract relevant information from cell culture samples that were simply lyzed. By using the recombinant adenovirus production process as a model, we were able to follow the accumulation of the three major proteins produced, identified their accumulation dynamics, and draw useful conclusions from these results. The combination of LCMS and MA provides a simple, rapid, and precise means to monitor cell culture. Appl Biochem Biotechnol (2012) 167:474–488 DOI 10.1007/s12010-012-9661-4 Both François-Thomas Michaud and Pierre Claver Havugimana contributed equally to this work. F.-T. Michaud Feldan Inc., 4975 Rideau Street, Québec, QC, Canada G2E 5H5 P. C. Havugimana : C. Duchesne : A. Garnier (*) Département Génie Chimique, Université Laval, 1065 Ave. de la Médecine, Québec, QC, Canada G1V 0A6 e-mail: alain.garnier@gch.ulaval.ca F. Sanschagrin Département de Biologie Médicale, Hôpital du Saint-Sacrement, 1050 chemin Ste-Foy, Québec, QC, Canada G1S 4L8 A. Bernier Institut de Recherche en Biotechnologie (IRB), Conseil National de Recherche du Canada (CNRC), Montréal, Québec, Canada H4P 2R2 R. C. Lévesque Institut de Biologie Intégrative et des Systèmes, Université Laval, 1030 Ave. de la Médecine, Québec, QC, Canada G1V 0A6