Microarray-based MALDI-TOF mass spectrometry enables monitoring of monoclonal antibody production in batch and perfusion cell cultures

Robert F Steinhoff; Daniel J Karst; Fabian Steinebach; Marie R G Kopp; Gregor W Schmidt; Alexander Stettler; Jasmin Krismer; Miroslav Soos; Martin Pabst; Andreas Hierlemann; Massimo Morbidelli; Renato Zenobi

doi:10.1016/j.ymeth.2015.12.011

Microarray-based MALDI-TOF mass spectrometry enables monitoring of monoclonal antibody production in batch and perfusion cell cultures

Methods. 2016 Jul 15:104:33-40. doi: 10.1016/j.ymeth.2015.12.011. Epub 2015 Dec 18.

Affiliations

¹ Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
² Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
³ Bio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
⁴ Faculty of Chemical Engineering, University of Chemistry and Technology, 16628 Prague, Czech Republic.
⁵ Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland. Electronic address: zenobi@org.chem.ethz.ch.

PMID: 26707204
DOI: 10.1016/j.ymeth.2015.12.011

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.

Keywords: Antibody; Batch; Cell culture; IgG; MALDI; Perfusion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / isolation & purification*
Antibody Formation
Cell Culture Techniques / methods*
Molecular Weight
Protein Array Analysis / methods*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

Antibodies, Monoclonal