Quantitative Profiling and Mapping of Small Molecules by Laser Desorption-Ionization Mass Spectrometry: Combinations of Carbon-based Nano Matrices and Sample Preparation Protocols

The choices of matrices and the protocols of sample deposition are critical factors which are convolving with each other in the matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging. Previous reports on MALDI MS matrices only compared their performance in MS signal intensities, and provided the optical microphotos or MALDI MS images of the sample spots, lacking of quantitative evaluation. There is an urgent need to develop multivariate model to evaluate the performance of different combinations between matrices and sample protocols. Herein we report a weighted multivariate model for quantitative profiling combinations of matrices/protocols systematically. Our work includes three types of carbon-based nano matrices, such as two-dimensional graphite oxide (GO) nanosheets, one-dimensional carbon nanotubes (CNTs), and zero-dimensional graphite dots (GDs). Four representative sample protocols for MALDI MSI, including rapid evaporation, seed layer, sandwich, and dry droplet, are examined in our model. We select five important parameters: (1) planar dispersity grading by SEM, (2) planar fluorescence homogeneity, (3) coefficient variations in MS signals, (4) MS signal-to-noise ratio, and (5) planar MS signal heatmap grading, with individually assigned weights according to their significance in MSI performance. Calculation of the radar chart areas based on our model provides quantitative profiles for individual combinations. Among them, the dry droplet protocol using the matrix of GDs offers the largest radar chart area, indicating a favorable combination choice for MSI. This work proposes a multivariate model to systematically compare different combinations of matrices and sample protocols, promising a useful tool for mapping small molecules by LDI MS.