Mass spectrometry imaging of small molecules in biological tissues using graphene oxide as a matrix

With the development of matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), molecular interrogation of tissue sections over a wide mass range has become feasible, but small molecule analysis is still far from being fully reached due to the limited sensitivity and matrix interference. Herein, graphene oxide (GO) is used as a MALDI matrix to image small molecules in tissues in negative ion mode. Finally, 212 of molecules including 190 of lipids and 22 of low molecular weight metabolites were detected and spatially visualized in mouse brain tissue sections without the interference of matrix ions/clusters, and the structures of 69 of the lipids were confirmed by using in situ tandem mass spectrometry. A further application of GO matrix could reveal distinct spatio-molecular signatures in viable and necrotic tumor regions derived from a mouse breast cancer tissue. In addition, GO as a MALDI matrix has exhibited a better performance in MSI of lipids relative to N-(1-naphthyl) ethylenediamine dihydrochloride and 9-aminoacridine. [Display omitted] •Graphene oxide as a MALDI matrix could improve tissue imaging quality of small molecules.•212 of small molecules were spatially imaged in mouse brain tissue with high sensitivity.•MSI using graphene oxide as a matrix revealed metabolite heterogeneity in cancer tissue.