A solvent-free matrix application method for matrix-assisted laser desorption/ionization imaging of small molecules

Area of Science:

• Analytical Chemistry
• Biochemistry
• Pharmacology

Background:

• Matrix application is crucial for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI).
• Conventional wet matrix application methods pose challenges for small molecule imaging due to analyte loss and spreading.
• Existing methods often omit washing steps to prevent analyte removal, complicating salt management.

Purpose of the Study:

• To develop and evaluate a dry matrix application method for MALDI-MSI of small molecules.
• To compare the effectiveness of dry matrix application against conventional wet methods.
• To explore the potential of post-application atmospheric exposure to enhance molecular visualization.

Main Methods:

• Development of a dry matrix application technique using finely divided matrix powder.
• Application of the dry matrix method to tissue samples for MALDI-MSI.
• Imaging of drug compounds, including clozapine in rat kidney and a diazabicyclononane derivative in rat brain.
• Exposure of dry matrix-coated samples to a saturated moist atmosphere.

Main Results:

• Dry matrix application provides a complementary approach to wet matrix methods for small molecule MALDI-MSI.
• This technique yields different ion profiles compared to wet application.
• Visualization of compounds not detectable with conventional wet matrix application was achieved.
• Post-application moist atmosphere exposure revealed an additional set of molecules.

Conclusions:

• Dry matrix application is a valuable alternative for MALDI-MSI of small molecules, particularly drugs and metabolites.
• The method overcomes limitations associated with analyte loss and spreading in wet application techniques.
• Further optimization, including atmospheric exposure, can expand the scope of detectable molecules in MALDI-MSI.