In situ, real time analysis of spatial molecular information from biological samples
Ambient Ionization and FAIMS Mass Spectrometry for Enhanced Imaging of Multiply Charged Molecular Ions in Biological Tissues
Clara L. Feider, Natalia Elizondo and Livia S. Eberlin
Direct analysis using mass spectrometry is now possible thanks to ambient ionization mass spectrometry imaging. This family of techniques provides in situ, real time analysis of spatial molecular information from complex biological material like tissue samples. Increasingly, direct analysis is finding applications in cancer diagnosis, as well as the characterization and distribution of lipids and metabolites in samples.
The chemical complexity of natural samples provides an inherent challenge in the application of direct analysis techniques, which prevents comprehensive detection and characterization of molecular species. Isobaric interferences in the mass spectrum of a sample complicate tandem MS analysis for structural characterization and obscures visualization of an ion’s spatial distribution.
In this study, issues relating to sample complexity in direct analysis are overcome using an ultraFAIMS system. The ultraFAIMS chip acts like a tuneable filter, allowing selective transmission of subsets of ions or classes of molecules. This is achieved by separating gas phase ions at atmospheric pressure on the basis of differences in their mobilities in electric fields. This comes prior to mass spectrometric analysis, and is able to reduce chemical noise and to improve signal-to-noise ratios, (S/N), sensitivity, and dynamic range.
ultraFAIMS was integrated with both DESI-MS (desorption electrospray ionization - mass spectrometry) and LMJ-SSP-MS (liquid-microjunction surface sampling probe - mass spectrometry) to image and characterize metabolites, glycerophospholipids, glycosphingolipids, and multiply-charged proteins in rat brain, human thyroid, and human ovarian cancer tissues (see example figures).
Using this approach, the authors show the first example of global protein imaging in human cancerous tissue by ambient ionization mass spectrometry imaging. The results indicate that integration of ultraFAIMS with DESI or LMJ-SSP is extremely valuable for imaging selected molecular classes in biological tissues.