| Lipids and low molecular weight metabolites(LMWMs)are essential constituents of organisms and participate in cellular metabolism and regulation,providing a functional readout of cellular state.A better understanding of the molecular composition of the cellular lipidome and metabolome can provide insight into the mechanism of physiological and pathological functions.However,due to the complexity of lipids and metabolites,with a large variety of categories,classes,subclasses,and molecular species,it is a great challenge to establish efficient analytical strategies for interrogation of the cellular compositional complexity.Recently,mass spectrometry imaging(MSI)has been developed rapidly as an in situ and label free analysis technique to obtain the spatial distribution information of various compounds in tissues.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.1.Mass spectrometry imaging of metabolites in biological tissues using graphene oxide as a matrixAs one of the most promising two-dimensional nanomaterials,graphene oxide(GO),with a single layer of carbon atoms,has shown excellent physical,chemical,optical and mechanical properties.Herein,GO was used as a MALDI matrix to image endogenous metabolites in tissues in negative ion mode.Finally,212 of molecules including 190 of lipids and 22 of LMWMs 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 in situ tandem mass spectrometry.Compared with N-(1-naphthyl)ethylenediamine dihydrochloride and 9-aminoacridine,GO as a MALDI matrix has exhibited better sensitivity and enhanced MSI performance for analysis of metabolites in tissue sections.Furthermore,MSI of a mouse breast cancer tissue revealed distinct spatio-specific molecular signatures in viable and necrotic tumor regions,including multiple lipid species and LMWMs.2.Ambient mass spectrometry imaging of metabolites in gastric cancer tissuesAmbient ionization mass spectrometry is undergoing rapid development because it enables detection of samples in a native environment without additional sample preparation.In previous study,we developed a method of liquid extraction electrosonic spray ionization(LEESSI)for ambient MSI.The high linear velocity of the nebulizing gas provides efficient desolvation of the charged liquid sample,and promotes the ionization of the desorbed analysts.When coupled with Fourier transform ion cyclotron resonance mass spectrometer(FTICR MS),high mass resolution and high spatial resolution imaging could be achieved within 3 hours.In this study,LEESSI ambient MSI was used for detecting the distributions of endogenous metabolites in gastric cancer tissues.Ion images coupled with multivariate statistical results revealed that the levels of FA(18:1),FA(18:2),FA(20:4),PG(16:0/18:1),PG(16:0/20:3),PG(16:0/20:4),PAHSA,OAHSA,POHSA,PI(16:0/18:1)and PI(18:1/18:1)were significantly up-regulated in cancerous areas,whereas levels of inosine and PE(20:1/22:6)were down-regulated in the same region.Our research indicates that LEESSI ambient MSI is a powerful tool for simultaneously investigating the distribution of metabolites in cancer tissues. |
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