Mass Spectrometry Imaging with Matrix-Enhanced SIMS: The Influence of Matrix Deposition Rate on Crystal Size and Signal Enhancement

Matrix-enhanced secondary ion mass spectrometry and matrix-assisted laser desorption/ionization are two mass spectrometry imaging techniques used to image biological molecules in cells and tissues. Both techniques utilize an organic matrix coating to enhance the detection of molecular ions. The homogeneity and crystal size of the matrix coating are critical for obtaining high quality images. Sublimation/deposition is currently widely used to apply a matrix layer onto a sample because of its ability to produce homogeneous layers with small crystal sizes. Additionally, the absence of a solvent during matrix application reduces lateral movement of the analyte. However, vertical migration of the analyte into the matrix coating is required to observe signal enhancement, and the factors that influence this migration are poorly understood. In this work, an in-house built sublimation matrix coater with a Knudsen effusion cell and sample cooling was used for controlled deposition of the matrix alpha-cyano-4-hydroxycinnamic acid onto a section of mouse brain cerebellum. Different deposition rates were used to coat two areas of the brain section with two different crystal sizes. Macro-scan images of the brain and 3D imaging of selected brain regions were performed. The results show differences in migration through the two matrix layers but also differences in analyte migration behavior for the same analyte in different tissue types.