Mass Spectrometry-based Tissue Imaging

Advanced Imaging in Biology and Medicine (Sensen CW and Hallgrimsson B eds. Springer. (2008) 131-146. ISBN: 978-3-540-68992-8)

Parker CE, Smith D, Suckau D and Borchers CH

In MALDI (matrix-assisted laser desorption/ionization) mass spectrom- etry, the sample consists of a thin film of proteins or peptides that has been cocrystallized with a matrix selected to “match” the frequency of a UV laser. The laser vaporizes and ionizes the sample, which is then mass-analyzed, typically in a time-of-flight (TOF) mass analyzer. Since the footprint of the laser is small, and the sample is a solid rather than a solution, it is easy to see how this led to the idea of “rastering” the laser across the sample to form a molecular image. After about ten years of development, MALDI imaging has finally come of age. This is partly due to newer MALDI-MS instrumentation that is capable of higher mass accuracy and resolution, as well as the development of MALDI- MS/MS for gas-phase sequencing. Several commercially-available sprayer/spotters have recently been developed which can produce a uniform coating of matrix on the sample. These sprayer/spotters can also be used to deposit enzyme solutions on targeted areas so that differentially-localized proteins can be identified. This chapter describes some of the recent work in MALDI imaging, as well as some of the clinical applications of this technique. Finally, a new technique is described (MRM MALDI) which allows the quantitationofdifferentially-localizedproteins on the basis of their peptide MS/MS spectra