Table 1.

Comparison of different MSI ionization methods.

Ionization	Advantages	Disadvantages
MALDI	10–100 μm spatial resolution, fmol-zmol sensitivity, mass resolution up to 40,000 Allows for analysis for a large mass range m/z 0 – 50,000 Da, allows for the generation of ions of small and large molecules. Has been used for quantitative analysis on tissue	Sample preparation and sample matrix required Matrix signals may interfere with the signal of analyte Low sensitivity for low molecular weight compounds Sample damage depending on the laser frequency
DESI	40–200 μm spatial resolution for DESI, 10–100 μm spatial resolution for nanoDESI, Ambient conditions, no vacuum required. Minimal sample preparation, no matrix required, faster analysis time	Low sensitivity for high m/z (>2000) ions At present, limited sample surface can be analyzed
SIMS	0.5–1 μm spatial resolution Static and dynamic ion modes provide surface and depth profile respectively	Low sensitivity for high m/z (>1000) ions due to fragmentation. Quantification is difficult
LA-ICP	Spatial resolutions < 1 μm possible Elemental imaging, trace metal detection and quantification Quantification of metal-labelled antibodies	Complex isotopic fractionation, isobaric interference lack of matrix matched standards for quantification Destructive action on the specimen