title: Microarray-based MALDI-TOF mass spectrometry enables monitoring of monoclonal antibody production in batch and perfusion cell cultures.
abstract: Cell culture process monitoring in monoclonal antibody (mAb) production is essential for efficient process development and process optimization. Currently employed online, at line and offline methods for monitoring productivity as well as process reproducibility have their individual strengths and limitations. Here, we describe a matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based on a microarray for mass spectrometry (MAMS) technology to rapidly monitor a broad panel of analytes, including metabolites and proteins directly from the unpurified cell supernatant or from host cell culture lysates. The antibody titer is determined from the intact antibody mass spectra signal intensity relative to an internal protein standard spiked into the supernatant. The method allows a semi-quantitative determination of light and heavy chains. Intracellular mass profiles for metabolites and proteins can be used to track cellular growth and cell productivity.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Steinhoff
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Karst
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Steinebach
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Marie R G
authors.initials: MR
authors.lastname: Kopp
authors.affiliation: Bio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
authors.forename: Gregor W
authors.initials: GW
authors.lastname: Schmidt
authors.affiliation: Bio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stettler
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Krismer
authors.affiliation: Faculty of Chemical Engineering, University of Chemistry and Technology, 16628 Prague, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Soos
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Pabst
authors.affiliation: Bio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hierlemann
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Massimo
authors.initials: M
authors.lastname: Morbidelli
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland. Electronic address: zenobi@org.chem.ethz.ch.
authors.forename: Renato
authors.initials: R
authors.lastname: Zenobi
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000302:isolation & purification*; D000917:Antibody Formation; D018929:Cell Culture Techniques / Q000379:methods*; D008970:Molecular Weight; D040081:Protein Array Analysis / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal
keywords: Antibody; Batch; Cell culture; IgG; MALDI; Perfusion