Journal of The American Society for Mass Spectrometry

, Volume 24, Issue 9, pp 1396–1404 | Cite as

Mass Discrimination in High-Mass MALDI-MS

  • Simon Weidmann
  • Gediminas Mikutis
  • Konstantin Barylyuk
  • Renato ZenobiEmail author
Research Article


In high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), the accessible m/z range is limited by the detector used. Therefore, special high-mass detectors based on ion conversion dynodes (ICDs) have been developed. Recently, we have found that mass bias may exist when such ICD detectors are used [Weidmann et al., Anal. Chem. 85(6), 3425–3432 (2013)]. In this contribution, the mass-dependent response of an ICD detector was systematically studied, the response factors for proteins with molecular weights from 35.9 to 129.9 kDa were determined, and the reasons for mass bias were identified. Compared with commonly employed microchannel plate detectors, we found that the mass discrimination is less pronounced, although ions with higher masses are weakly favored when using an ICD detector. The relative response was found to depend on the laser power used for MALDI; low-mass ions are discriminated against with higher laser power. The effect of mutual ion suppression in dependence of the proteins used and their molar ratio is shown. Mixtures consisting of protein oligomers that only differ in mass show less mass discrimination than mixtures consisting of different proteins with similar masses. Furthermore, mass discrimination increases for molar ratios far from 1. Finally, we present clear guidelines that help to choose the experimental parameters such that the response measured matches the actual molar fraction as closely as possible.

Key words

Relative response factor Mass discrimination MALDI-TOF-MS High-mass protein analysis Ion conversion dynodes 



The authors thank the initiative (CINA grant) and the Swiss National Science Foundation (grant no. 200020–124663) for their financial support. G.M. was supported by a Swiss Government Excellence Scholarship (2011–2013). The authors also thank Stefanie Mädler (currently at York University, Toronto, Canada) and Nadezhda Nespovitaya (ETH Zürich, Switzerland) for their help with the design and synthesis of the MBP3 polyproteins, and the Plückthun Lab (University of Zürich, Switzerland) for the generous gift of the DARPin samples.


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Copyright information

© American Society for Mass Spectrometry 2013

Authors and Affiliations

  • Simon Weidmann
    • 1
  • Gediminas Mikutis
    • 1
  • Konstantin Barylyuk
    • 1
  • Renato Zenobi
    • 1
    Email author
  1. 1.Department of Chemistry and Applied BiosciencesETH (Swiss Federal Institute of Technology) ZürichZürichSwitzerland

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