MALDI Matrix: Origins, Innovations, and Frontiers

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and its imaging variant (MALDI-MSI) are pivotal analytical tools for biological sample analysis, allowing detection and visualization of diverse biomolecules. At the heart of MALDI-MS/MSI performance lies the crucial yet often empirically determined choice of matrix. A suitable matrix not only boosts analyte ionization efficiency but also enhances sensitivity, salt tolerance, and overall applicability, which are key for specific compound detection. To date, a cumulative total of 467 matrices have been successfully discovered and developed. However, merely a handful of them have achieved widespread utilization, which strongly suggests that there remains a substantial reservoir of untapped potential within this domain. This review offers a systematic and comprehensive overview of MALDI matrices over four decades (1985-present). It starts by outlining MALDI-MS analysis principles and procedures, providing a basis for understanding matrix functions. Then, matrices are systematically classified according to their features. We also spotlight recent matrix applications in MALDI-MS detection and imaging in proteomics, lipidomics, metabolomics, glycomics, nucleic acid analysis, and quantitative analysis. Finally, we chart future research directions, aiming to unlock the full potential of matrices in this dynamic field.