MASS2 · Modern Au-based Surfaces and Secondary ionisation for Mass Spectrometry Imaging of Small molecules

Modern Au-based Surfaces and Secondary ionisation for Mass Spectrometry Imaging of Small molecules

Matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry imaging (MSI) is a modern analytical technique that can map the distribution of numerous biochemical substances in tissue sections. It is increasingly used in life science research as in clinical application due to the untargeted and comprehensive approach that can yield superior density of information compared to conventional histology techniques. However, MALDI inherently suffers from several major limitations such as low ion yields limited to a few classes of polar to mid-polar analytes, strong ion suppression effects, and an impeded detection of low-weight compounds. This hampers the comprehensive analysis for complex biomedical questions. Thus, technical advancements seek to overcome these limitations: Surface-assisted LDI (SALDI) uses photoactive surfaces with unique ablation and ionisation features that can majorly extend the range of detectable compounds, whereas Postionisation (PI) can significantly increase the ion yields for numerous compounds and level out ion suppression. Both techniques have demonstrated their power for MSI application. MASS2 - Modern Au-based Surfaces and Secondary ionisation for Mass Spectrometry Imaging of Small molecules - aimed to develop a novel means for extensive metabolome and lipidome analysis by SALDI-PI-MSI to overcome limitations of MALDI. For this, the first Objective dealt with the successfully combination of a new PI strategy coined Single-Photon Induced Chemical Ionisation (SPICI) with functionalised Au layers. With this, the chemical coverage of compounds in biomedical tissue sections could be extended, especially for an extended mass range below 500 Da, and with high mass and spatial resolution. Objective 2 aimed for the parameter optimisation and identification of key settings for a comprehensive analysis. As a result, a large number of endogenous analytes were detected that could not be detected with conventional MALDI-MSI or SALDI-MSI systems before. Complex data outputs were analyzed with the versatile in-house developed software package rMSI that facilitated routine data mining, in Objective 3. The new technical possibilities were demonstrated in the analysis of two sample systems of high relevance in the life science research in Objective 4. First, MASS2 allowed monitoring of physiological processes in tumor tissue sections from human bladder cancer at unprecedented analytical depth. Newly identified biomarkers will help the urgent need for prognostic and diagnostic means for cancer. Second, an optimized sample protocol for the analysis and comprehensive spatial biochemical characterisation of zebra fish embryos was developed. This can now serve as a fast and scalable template for, e.g., future toxicology/exposome studies. These comprehensive approaches generate massive data that will reveal new insight of physiological processes underlying the interaction of toxicants with metabolism MASS2 allowed for the creation of a platform to offer these advanced services to cooperation partners in the local and national biomedical research network and contribute to major discoveries in life sciences in comprehensive, multidisciplinary fashion.

Data: CORDIS, © European Union