Project Details
Projekt
High resolution MALDI mass spectrometry imaging with laser-induced postionization
Subject Area
Analytical Chemistry
Term
from 2016 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 290343045
MALDI mass spectrometry imaging (MALDI-MSI) enables simultaneous label-free recording of numerous biomolecules such as lipids, peptides, and metabolites directly from matrix-coated tissue slices. However, limited ion yields and ion suppression effects often restrict the applicability of the method, not least in high resolution applications where only little material is available per irradiated pixel. We recently introduced an extension of conventional MALDI, called MALDI-2. By using a second laser and a fine-vacuum ion source, MALDI-like secondary ionization processes could be initiated and the MSI signal intensities of - so far - lipids, glycoconjugates and liposoluble vitamins increased by up to two orders of magnitude [Soltwisch et al., Science 348 (2015) 211]. The research project aims at the development of this innovative technology and at obtaining a deeper knowledge about the processes underlying MALDI-2. Therefore, it can be broken down into two closely linked sections:Within the first main part >Methodisch-instrumentelle Entwicklungen und Anwendungen< we seek to further increase the analytical sensitivity for different classes of analytes, among others by using a Nd:YAG laser of high beam intensity, the development of improved MALDI-2 matrix systems, and by use of direct resonant 2-photon ionization for the analysis of metabolites. In this context, we will also explore whether metabolites could be postionized efficiently that are desorbed from tissue by means of direct IR-laser desorption. In a further section of the work program we seek to improve the lateral resolution to values of 1-2 µm by coupling MALDI-2 with the so-called transmission mode geometry. In collaboration with leading colleagues, the optimized technique will also be applied to a few selected biomedical research questions, among others for an improved visualization of glycolipids, serving as receptors for pathogenic microorganisms and their toxins.Within the fundamental investigations of the second main part >Mechanismen der MALDI-2< the processes of material ablation and ionization will be studied. We will characterize which physico-chemical properties of a MALDI-Matrix arre equired to enable an effective postionization, invrstigate which analyte classes are in principle amenable to MALD-2 and to direct 2-photon ionization, and optimize postionization irradiation conditions in both cases. By conducting extended wavelength studies, fine features of the ionization processes will be revealed and by characterizing the expansion dynamics of the material plume at varying experimental conditions, such as different focal diameters of the desorption laser beam, pressure of the buffer gas in the ion source, and the type oft excitation (top illumination vs. transmission mode geometry / UV- vs. IR-laser desorption), further important insight into the MALDI-2 mechanisms will be obtained.
DFG Programme
Research Grants
Major Instrumentation
ps-Nd:YAG-Laser (266 nm)
Instrumentation Group
5700 Festkörper-Laser
