A Novel Soft Ionization Process and Applications in Imaging Mass Spectrometry

Abstract

A motivation of our research is to make inroads in the daunting task of chemical analysis of the brain's composition and temporal changes. We recently introduced a new soft ionization process for use in mass spectrometry (MS). This new technique called laserspray ionization (LSI) has advantages of speed of analysis, high spatial resolution for imaging, mass range extension, and improved fragmentation common with multiply charged ions. We have interfaced LSI with ion mobility spectrometry (IMS) for separation of gas phase ions from mixtures by charge and cross-section (size/shape) and, in a second dimension, with high resolving power by mass-to-charge permitting powerful deconvolution of sample complexity, even with identical masses (isomers), directly from surfaces. LSI interfaced with mass spectrometers having electron transfer dissociation (ETD) capabilities produces similar backbone fragmentation as ESI as demonstrated for the protein ubiquitin as well as for peptides directly from tissue. We have extended LSI to vacuum mass spectrometers and determined that ionization occurs with vacuum or thermal assistance without the need of voltage or lasers. LSI imaging of mouse brain tissue sections is demonstrated to determine the location of gadolinium-based complexes synthesized for use as magnetic resonance imaging (MRI) agents. Conventional MALDI failed. The LSI images are complemented by MRI and microscopy results of the same mouse brain and, additionally, provide a molecular view of the endogenous chemical composition. MS images of mouse brain tissue from a clozapine treated mouse are compared with results obtained for endogenous lipids, peptides and small proteins in the same tissue. Protocols are being developed for high spatial resolution LSI imaging.