Detection of Lipids in the MALDI Negative Ion Mode for Diagnostics, Food Quality Control, and Antimicrobial Resistance

Abstract

Over recent decades, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has revolutionized clinical diagnostics worldwide. It is commonly based on the fingerprints of cytosolic proteins, mainly ribosomal proteins, and their detection in positive ion mode. This is due to the intrinsic properties of proteins, which ionize efficiently in positive ion mode compared with other classes of molecules, such as lipids and glycolipids. However, due to the focus and limitations of using solely positive ion mode, data that could be used to address the unmet needs of clinical diagnostics, for example, by adding information provided by negative ion mode, are underexplored. In addition to positive ion mode, MALDI in negative ion mode has the potential to address current challenges in several areas, such as clinical microbiology diagnostics and food safety. By acquiring data not only in positive ion mode but also in negative ion mode, greater coverage of molecules can be achieved. The additional molecules include common phospholipids, glycolipids, and species-specific lipids found in the membrane and cell envelope of the specimens studied or in their composition. In this chapter, we report on the application of the detection of lipids by MALDI, particularly routine MALDI in negative ion mode, in key areas for routine clinical microbiology diagnostics, the detection of drug resistance, cancer diagnostics, and food fraud. Taken together, combining the use of lipids and their detection, the negative ion mode with positive ion mode data will certainly be a gold standard for future routine MALDI mass spectrometry applications.