A review of complementary separation methods and matrix assisted laser desorption ionization-mass spectrometry imaging: Lowering sample complexity

• Combination of MS imaging and separations reveals more sample composition.
• Mass spectrometry images chromatography.
• Separation improves mass spectrometry imaging results.

Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) brings unique combined information on molecular identity and molecular distribution of a sample surface. During the past decade, it has matured and is now routinely employed for biomedical tissue sections analysis. However, owing to the high molecular complexity of tissue, MALDI-MSI suffers from ionization suppression effects. This directly results in a reduced ability to detect low-abundant molecular species. At the same time, the spatial resolution of separation techniques can be insufficient for an unambiguous determination of the local composition of a mixture. As analytical separation techniques can significantly reduce ion suppression, and MALDI-MSI has an ability to improve their spatial resolution, the two analytical approaches can successfully be combined in a pursuit of comprehensive local sample composition information. In the following review we summarize strategies of mutually beneficial combinations of MALDI-MSI and different separation techniques and discuss limitations and future developments.