Automated solvent-free matrix deposition for tissue imaging by mass spectrometry

The ability to analyze complex (macro) molecules is of fundamental importance for understanding chemical, physical, and biological processes. Complexity may arise from small differences in structure, large dynamic range, as well as a vast range in solubility or ionization, imposing daunting tasks in areas as different as lipidomics and proteomics. Here, we describe a rapid matrix application that permits the deposition of matrix-assisted laser desorption/ionization (MALDI) matrix solvent-free. This solvent-free one-step automatic matrix deposition is achieved through vigorous movements of beads pressing the matrix material through a metal mesh. The mesh (20 mum) produces homogeneous coverage of <12 microm crystals (DHB, CHCA matrixes) in 1 min, as determined by optical microscopy, permitting fast uniform coverage of analyte and possible high-spatial resolution surface analysis. Homogenous tissue coverage of <5 microm sized crystals is achieved using a 3 microm mesh. Solvent-free MALDI analysis on a time-of-flight (TOF) mass analyzer of mouse brain tissue homogenously covered with CHCA matrix subsequently provides a homogeneous response in ion signal intensity. Total solvent-free analysis (TSA) by mass spectrometry (MS) of tissue sections is carried out by applying the MALDI matrix solvent-free for subsequent ionization and gas phase separation for decongestion of complexity in the absence of any solvent using ion mobility spectrometry (IMS) followed by MS detection. Isobaric compositions were well-delineated using TSA by MS.