In Situ Hydrogel Conditioning of Tissue Samples To Enhance the Drug’s Sensitivity in Ambient Mass Spectrometry Imaging

Ion suppression from the tissue matrix has a severe effect on the mass spectrometry imaging (MSI) of drugs. This problem hinders further applications of MSI in preclinical drug research and development. In this study, an in situ hydrogel conditioning method was developed to enhance the sensitivity of air-flow-assisted desorption electrospray ionization (AFADESI)-MSI. Instead of the traditional washing or digestion treatment in solvent, this method used a solid phase hydrogel to “wash” tissue sections. It was demonstrated that this in situ hydrogel conditioning method improved the drug signal by as much as 2- to 25-fold in MSI, especially for hydrophobic compounds. Furthermore, the obvious dislocation of analytes was not observed. The evaluation of spatial resolution indicated that the amount of dislocation in tissue sections with the hydrogel process was less than the resolution of AFADESI-MSI. The underlying reasons for the MSI signal enhancement were initially investigated. The decreased signal intensit...