Matrix-assisted
laser desorption/ionization (MALDI) mass spectrometry
imaging (MSI) is used for the multiplex detection and characterization
of diverse analytes over a wide mass range directly from tissues.
However, analyte coverage with MALDI MSI is typically limited to the
more abundant compounds, which have m/z values that are distinct from MALDI matrix-related ions. On-tissue
analyte derivatization addresses these issues by selectively tagging
functional groups specific to a class of analytes, while simultaneously
changing their molecular masses and improving their desorption and
ionization efficiency. We evaluated electrospray deposition of liquid-phase
derivatization agents as a means of on-tissue analyte derivatization
using 2-picolylamine; we were able to detect a range of endogenous
fatty acids with MALDI MSI. When compared with airbrush application,
electrospray led to a 3-fold improvement in detection limits and decreased
analyte delocalization. Six fatty acids were detected and visualized
from rat cerebrum tissue using a MALDI MSI instrument operating in
positive mode. MALDI MSI of the hippocampal area allowed targeted
fatty acid analysis of the dentate gyrus granule cell layer and the
CA1 pyramidal layer with a 20-μm pixel width, without degrading
the localization of other lipids during liquid-phase analyte derivatization.