title: Cell culture tracking by multivariate analysis of raw LCMS data.
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.
authors.affiliation: Feldan Inc., 4975 Rideau Street, Québec, QC, Canada G2E 5H5.
authors.forename: François-Thomas
authors.initials: FT
authors.lastname: Michaud
authors.forename: Pierre Claver
authors.initials: PC
authors.lastname: Havugimana
authors.forename: Carl
authors.initials: C
authors.lastname: Duchesne
authors.forename: François
authors.initials: F
authors.lastname: Sanschagrin
authors.forename: Alice
authors.initials: A
authors.lastname: Bernier
authors.forename: Roger C
authors.initials: RC
authors.lastname: Lévesque
authors.forename: Alain
authors.initials: A
authors.lastname: Garnier
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods*; D002498:Centrifugation; D002853:Chromatography, Liquid / Q000379:methods*; D004274:DNA, Recombinant / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D015999:Multivariate Analysis; D012984:Software; D012995:Solubility; D013997:Time Factors; D014771:Virion / Q000378:metabolism
chemical_list: D004274:DNA, Recombinant