Mass spectrometry (MS) is already perhaps the most popular analytical chemistry tool in drug discovery and development. Its use is ubiquitous in bioanalytical laboratories for drug and metabolite quantitation, and it has enabled rapid advances in global protein profiling and disease biomarker discovery. The implementation of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) have been catalysts for the rapid expansion of MS-based applications.
ESI enables solution-phase analytes to be introduced as ions into the mass spectrometer for mass analysis, while MALDI creates ions of the analytes in the sample under vacuum conditions by sublimation of a crystalline matrix using laser pulses. Developments in the MALDI method over the last ten years have resulted in the ability to image intact tissue sections for proteins and peptides.
The analysis of tissue samples by MALDI for small molecules is particularly challenging given the high chemical background that results from having to prepare the tissue section with a suitable matrix for proper extraction and crystallization of the analyte. The time, skill, and equipment required for proper sample preparation can also be cumbersome. As a result, new methods for direct sample analysis have been developed that aim to circumvent some of these challenges.
Until very recently it was considered impossible to sample and image surfaces with mass spectrometry at ambient pressures and temperatures. This tutorial will explore the principles of desorption electrospray ionization (DESI) mass spectrometry, which has been used to scan across the surface of a tablet, image an untreated tissue section with 230 µm lateral resolution, and was even featured on the television series CSI:Miami to image a latent fingerprint.