Biomedical Engineering Reference
In-Depth Information
Mass Spectrum Acquired at each Position
Matrix Spotted
Tissue Sample
Ion Density Maps
Intensity
Figure 13.3
Schematic of a MALDI-IMS experiment. Intact tissue (cryostat thin-section) is
mounted on a MALDI target and overlaid with matrix. Individual MALDI-MS spectra are acquired
at individual positions across the tissue at high resolution. The enlarged MS spectrum contains
singly charged molecular ions that can be mapped across the tissue by intensity. The intensity
distribution for four individual species is shown below. Image courtesy of R.M. Caprioli and
R. Groseclose.
between tissue sections, and statistically-significant signatures indicative of disease can be
identified [51, 52]. This approach has been particularly useful to investigate prognostic
and diagnostic markers for a variety of cancers [51, 53-58]. Proteins that give rise to the
molecular signals of interest can be biochemically isolated from the intact tissue, enabling
identification using the standard peptide-based protein identification strategies described
above.
Another commercially available MALDI-based profiling platform, surface-enhanced laser
desorption ionization (SELDI), is used for serum and other biofluid analysis [59-61]. The
main feature of SELDI is several different proprietary sample preparation methods that
simplify/enrich the protein mixture based on different physicochemical parameters (i.e.
hydrophobicity, ionic interaction, metal affinity [59-61]). This approach continues to be
employed in many research studies, with several technical studies devoted to issues regard-
ing experimental design and reproducibility [62-64].
13.2.3.1 Imaging: Procedure and applications
•
Resolution of molecular ions of intact protein species directly from intact samples (e.g.
tissue thin-sections) in a mass spectrometer.
•
Retains spatial information across intact tissue.
•
Can be run in both high-resolution mode (imaging) and low-resolution mode (profiling).
•
Can be directly correlated with histology on intact tissue.
•
Is directly amenable to independent replicates from multiple experimental conditions, as
well as multivariate statistical analysis.
