Prof. Sebastiaan van Nuffel

Maastricht University, Netherlands
Throughout his scientific career, Sebastiaan Van Nuffel has built up extensive expertise in imaging mass spectrometry, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and its application in biological and medical research. He completed his PhD at the University of Nottingham in the UK. He then worked as a postdoctoral researcher at the French National Center for Scientific Research, followed by a second postdoc at the Pennsylvania State University in the US. Currently, he holds the position of Assistant Professor (tenured) at the Faculty of Science and Engineering and is embedded in the Maastricht MultiModal Molecular Imaging (M4i) at the Maastricht University in the Netherlands.

Talk title: Investigating biointerfaces using integrative ToF-SIMS imaging
Dr. Sebastiaan Van Nuffel is presenting various examples of the ongoing research in his group using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) imaging. ToF-SIMS is an ultra-high vacuum (UHV) technique capable of analyzing the top 1-3 monolayers of a surface. For the past two decades, ToF-SIMS imaging in particular has successfully answered various research questions, because it can visualize the spatial distribution of small molecules (< 2000 Da) in 2D with a spatial resolution comparable to that of a light microscope. Through ion beam sputtering, it is also possible to depth profile and create 3D image stacks with a depth resolution down to 5-10 nm. ToF-SIMS imaging can be used to simultaneously investigate the elemental composition, the metabolome and the lipidome of single cells and tissue sections as well as their interaction with non-native compounds such as drugs or toxins. Furthermore, as ToF-SIMS can observe inorganic and organic compounds, it is also eminently suited for research involving biointerfaces.

Although ToF-SIMS allows for label-free detection, ambiguity always remains with regards to structural identification of compounds given the secondary ions of the different compounds present in the sample are all formed together after the impact of the primary ion. Consequently, a typical ToF-SIMS mass spectrum can be considered a summation of the spectra of the individual compounds present and spatial colocation does not necessarily mean that these mass peaks all originate from one compound. Luckily, the creation of ToF-SIMS instruments with MS/MS capabilities makes unambiguous identification finally possible. Regardless, the data generated is very complex, especially in the case of biological systems, and its integration with multivariate analysis techniques for image segmentation and more advanced machine learning approaches for biomarker discovery will be covered as well. In addition, it is difficult to detect large molecules such as intact proteins with a typical ToF-SIMS instrument. It is therefore necessary to integrate ToF-SIMS with other techniques such immunohistochemistry in order to establish a spatially resolved multi-omics atlas. However, there are several issues still hampering its widespread application. In order to become truly competitive with immunofluorescence microscopy, the same field of view needs to be achieved at a similar throughput rate. Ongoing research efforts developing SIMS-IHC methods in combination with novel stigmatic SIMS imaging instrumentation will be discussed.