Characterising the structures of polymers using ion mobility-mass spectrometry

  • Florian Benoit

Student thesis: Phd


Polymers have developed significantly over the last decade in a variety of fields in order to address challenges in materials science, biotechnology and medicine. Drug delivery is an exemplar application in which linear and dendritic polymers are involved in the design of polymer-drug conjugates. Molecular structure and conformation are key parameters which ensure the physical stability and biological activity of pharmaceutically relevant materials. Electrospray ionisation (ESI) and nanoelectrospray ionisation (nESI) mass spectrometry (MS) techniques have recently evolved to enable high-resolution mass measurements of low concentration samples. The inclusion of ion mobility-mass spectrometry (ESI/nESI-IM-MS) allows for the calculation of collision cross sections (CCSs) that provide insight into the size and shape of gas-phase ions. In addition, this technique can further facilitate the separation of isobaric compounds in the analysis of unknown species and/or complex mixtures. Firstly, linear amino acid-based polymers are studied using MS and IM-MS workflows. The molecular weight distributions of polydisperse polyalanine, polylysine, polyglutamic acid and polyarginine measured by MS and IM-MS are compared to the expected ranges with ESI, nESI and matrix-assisted laser desorption/ionisation (MALDI). Discrepancies are observed in which higher molecular weights are not detected, namely due to peptide fragmentation. The use of a deconvolution algorithm supplements the MS results and provides more detailed information. Secondly, polylysine dendrimers of generation 1 to 6 are structurally investigated with MS and IM-MS techniques. Accurate mass measurements are enabled by nESI-MS analysis through formation of multiply charged ions. Moreover, the charge state dictates gas-phase conformation as evidenced by distinct monomodal CCS distributions. A linear increase in the CCS of high generation dendrimers (4 to 6) is observed with charge. Lastly, the conformational stability of dendrimers is investigated by activated IM-MS and variable temperature (VT) IM-MS. The rigidity observed for these molecules under thermal and collisional activations alongside wide m/z and CCS ranges make them systems of interest for IM-MS calibration purposes. This thesis explores the benefits of using MS and IM-MS techniques to characterise a variety of polymers in structure across a wide range of instrumentation.
Date of Award1 Aug 2021
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorJames Warwicker (Supervisor) & Perdita Barran (Supervisor)


  • structural analysis
  • ion mobility-mass spectrometry
  • polymer
  • mass spectrometry
  • ion mobility

Cite this