Electric Field-Assisted Matrix Coating Method Enhances the Detection of Small Molecule Metabolites for Mass Spectrometry Imaging.

Small molecule metabolites (SMMs, typically <500 Da) are important cellular constituents closely associated with tumor development and progression. However, in situ label-free detection of tissue SMMs has been limited due to interference from matrix and/or low sensitivity. Herein, we develop an electric field-assisted scanning-spraying (EFASS) matrix coating system to deposit matrix on tissue with crystal sizes of <10 μm, followed by matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in negative ion mode. A comparison with other matrix deposition methods (i.e., airbrush and sublimation) using common matrixes (i.e., N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC), 9-aminoacridine (9-AA), 2,5-dihydroxybenoic acid (DHB)) indicated that the EFASS system could effectively enhance detection sensitivity and the number of tissue SMMs detected. MSI of five gastric cancer tissues coated with NEDC by the EFASS system demonstrated that significantly increased levels of fatty acids (i.e., palmitic acid and oleic acid) and nucleosides monophosphate (i.e., uridine monophosphate, adenosine monophosphate, and guanosine monophosphate) and significantly decreased levels of nucleosides (i.e., inosine, guanosine, and uridine) and N-acetylneuraminic acid were observed in cancerous areas.