A Five-Year Update on Matrix Compounds for MALDI-MS Analysis of Lipids

Abstract

Matrix-assisted laser desorption and ionization (MALDI) is a widely used soft-ionization technique of modern mass spectrometry (MS). MALDI enables the analysis of nearly all chemical compounds—including polar and apolar (phospho)lipids—with a minimum extent of fragmentation. MALDI has some particular advantages (such as the possibility to acquire spatially-resolved spectra) and is competitive with the simultaneously developed ESI (electrospray ionization) MS. Although there are still some methodological aspects that need to be elucidated in more detail, it is obvious that the careful selection of an appropriate matrix plays the most important role in (lipid) analysis. Some lipid classes can be detected exclusively if the optimum matrix is used, and the matrix determines the sensitivity by which a particular lipid is detected within a mixture. Since the matrix is, thus, crucial for optimum results, we provide here an update on the progress in the field since our original review in this journal in 2018. Thus, only the development during the last five years is considered, and lipids are sorted according to increasing complexity, starting with free fatty acids and ending with cardiolipins and phosphoinositides.

Matrix Selection for the Visualization of Small Molecules and Lipids in Brain Tumors Using Untargeted MALDI-TOF Mass Spectrometry Imaging

“…Matrices, such as 1,5-diaminonapthalene (DAN), which was used to obtain spatial metabolomics followed by immunohistochemistry on rat brain sections [45], and 2,4,6-trihydroxyacetophenone (THAP) [13], which performed well in a recent evaluation on normal brain tissue of six different matrices, should also be evaluated in future comparative studies for their suitability for the analysis of metabolic activity in brain cancer. Additionally, future studies should test matrices with additives, such as ionic liquid matrices, that are known to improve MALDI analysis [46,47]. We recommend that future comparative studies follow our experimental and computational workflow to evaluate the performance of different matrices and deposition techniques.…”

Combining imaging mass spectrometry and immunohistochemistry to analyse the lipidome of spinal cord inflammation

“…Negative polarity was chosen as it enables the detection of species from a larger number of lipid classes, and the spectra are easily to annotate, due to the presence of a reduced number of adducts [ 11 , 45 , 46 ]. Among the large number of matrices available to work in this polarity [ 47 , 48 ], we chose DAN, as its deposition by sublimation results in uniform films of small crystals, and it has demonstrated to produce excellent signal intensity with a low background [ 49 ].…”

Matrix- and Surface-Assisted Laser Desorption/Ionization Mass Spectrometry Methods for Urological Cancer Biomarker Discovery—Metabolomics and Lipidomics Approaches

“…Another aspect of the studies presented here is the frequent absence of comparative analysis between the positive and negative ion modes. This is challenging in the case of MALDI, due to the necessity of using different matrices for these two modes, as seen in lipid analyses [ 81 ], and for SALDI, the topic of negative mode is practically unaddressed in scientific publications. This is significant for future experiments aimed at determining the full metabolomics or lipidomics profiles of tumors using LDI methods and may contribute to the improved coverage of metabolites or lipids in subsequent analyses.…”