Advanced methods for MALDI mass spectrometry imaging for single cell analysis at cellular and subcellular resolution

• Applicant: Privatdozent Dr. Jens Soltwisch
• Subject Area: Analytical Chemistry ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544444139

MALDI-MS imaging is a rapidly evolving tool for the spatially resolved molecular analysis of biological samples such as tissue sections. In recent years, improvements of sensitivity and depth of information on the one hand and increased spatial resolving power on the other have enabled the meaningful analysis of single cells. Here, a close connection between microscopy methods and high resolving power MALDI-MSI allows generating single cell mass spectra that are unambiguously linked to a specific cell. The proposed project aims to further advance, translate, and transform innovative MALDI-MSI techniques for the analysis of a number of analyte classes recently developed in our group into expedient analytical tools and methods for research in single cell analysis. In particular, the project will target the gap between experimental developments and proof-of principle studies and their applicability to pressing real-life analytical questions and challenges from the biomedical laboratory or the clinics. It is aimed to demonstrate the usefulness of MALDI-2-MS imaging (including t-MALDI-2-MSI) at high (pixel size < 10 micrometers) and very high spatial resolution (pixel size < 2 micrometers) for single cell analysis. Next to sensitive and highly resolved MSI, single cell analysis requires a tight coupling of the generated data to light optical modalities. An important focus of the project therefore lays on the advancement MALDI-compatible microscopy and a seamless integration of state-of-the-art tools for co-registration and microscopy based segmentation as well as identification of specific cells. In particular, this may also include the advanced use of optical methods like microscopy inside the ion source. To demonstrate the potential of single cell mass spectrometry the project will investigating specific questions and tasks from the field of cellular biology. This work will be done in collaboration with leading experts within the University of Münster and the University Hospital and will center on cells of the immune system and their response to inflammatory stimuli.

• DFG Programme: Research Grants
• International Connection: Netherlands
• Cooperation Partner: Professor Dr. Benjamin Balluff