Glycomics imaging

Mass spectrometry imaging (MSI) is an evolving field which combines the advantages of mass spectrometry with spatial, label-free compound visualization – making it a powerful tool to investigate tissue biology and the linked pathology. Recently, a platform for the analysis of N-glycans by MALDI-MSI has been pioneered by Drake et al., which was successfully transferred to the LUMC CPM and developed further. Current projects address different challenges in the field of (glycomic) MSI including the reliable detection of sialic acids, reducing valuable sample material, expanding the technique to other glycan classes and absolute quantification. Additionally, the application of glycan MSI for clinical research is in our focus.

Differentiation of sialic acid linkage isomers of N-glycans in mass spectrometry imaging of a colon tumor.1

Together with the colleagues around Prof. Drake as well as collaborators from the Department of Surgery and Pathology, we developed a workflow for the linkage-specific in-situ sialic acid derivatization in formalin-fixed paraffin-embedded (FFPE) tissues based on the protocol by Haan el al.1 This workflow successful stabilizes the sialic acids in a linkage specific manner, thereby increasing the biological information obtained from the analysis, while maintaining tissue integrity2 and is now applied to a small colorectal cancer cohort. Furthermore, we developed a sequential on-tissue digestion for the analysis of N-glycans and tryptic peptides from a single tissue section using high resolution MSI.3 This comprehensive approach offers great advantages with regard to reduction of valuable tissue material as well as comparability of two highly related molecule classes.

Different research activities on colorectal cancer and soft tissue sarcomas as well as pancreatic cancer and others are ongoing and further advancing our technologies is a constant progress. For example, we have recently been able to acquire the latest in MALDI imaging instrumentation, the RapiFlex (Bruker Daltonics).

  1. Holst, S. et al. Linkage-Specific in Situ Sialic Acid Derivatization for N-Glycan Mass Spectrometry Imaging of Formalin-Fixed Paraffin-Embedded Tissues. Anal. Chem. 88 (11), 5904-5913 (2016).
  2. de Haan, N. et al. Linkage-specific sialic acid derivatization for MALDI-TOF-MS profiling of IgG glycopeptides. Anal. Chem. 87 (16), 8284-91 (2015).
  3. Heijs, B. et al. Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section. Anal. Chem. 88 (15), 7745-53 (2016).