# MALDI Matrix: Origins, Innovations, and Frontiers

## TL;DR

This paper reviews the development and use of MALDI matrices in mass spectrometry, highlighting their role in improving detection and analysis of biomolecules.

## Contribution

The paper systematically classifies 467 MALDI matrices and identifies opportunities for future innovation in matrix design.

## Key findings

- Only a few of the 467 developed MALDI matrices are widely used, indicating untapped potential.
- Matrices significantly impact ionization efficiency, sensitivity, and salt tolerance in MALDI-MS.
- Recent applications span proteomics, lipidomics, and nucleic acid analysis.

## Abstract

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.