Titania Nanosheet as a Matrix for Surface-Assisted Laser Desorption/Ionization Mass Spectrometry Analysis and Imaging

Surface-assisted laser desorption/ionization (SALDI) acts as a soft desorption/ionization technique, which has been widely recognized in small-molecule analysis owing to eliminating the requirement of the organic matrix. Herein, titania nanosheets (TiO₂ NSs) were applied as novel substrates for simultaneous analysis and imaging of low-mass molecules and lipid species. A wide variety of representative analytes containing amino acids, bases, drugs, peptides, endogenous small molecules, and saccharide-spiked urine were examined by the TiO₂ NS-assisted LDI mass spectrometry (MS). Compared with conventional organic matrices and substrates [Ag nanoparticles (NPs), Au NPs, carbon nanotubes, carbon NPs, CeO₂ microparticles, and P25 TiO₂], the TiO₂ NS-assisted LDI MS method shows higher sensitivity and less spectral interference. Repeatability was evaluated with batch-to-batch relative standard deviations for 5-hydroxytryptophan, glucose-spiked urine, and glucose with addition of internal standard, which were 17.4, 14.9, and 2.8%, respectively. The TiO₂ NS-assisted LDI MS method also allows the determination of blood glucose levels in mouse serum with a linear range of 0.5-10 mM. Owing to the nanoscale size and uniform deposition of the TiO₂ NS matrix, spatial distributions of 16 endogenous small molecules and 16 lipid species from the horizontal section of the mouse brain tissue can be visualized at a 50 μm spatial resolution. These successful applications confirm that the TiO₂-assisted LDI MS method has promising prospects in the field of life science.