Mass Spectrometry-Based Tissue Imaging
In MALDI (matrix-assisted laser desorption/ionization) mass spectrometry, 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 quantitation of differentially-localized proteins on the basis of their peptide MS/MS spectra.
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