Dry Deposition Strategies for MALDI–MS Imaging: Principles, Advances and Emerging Applications

Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) has become a pivotal tool in biomedical research, enabling untargeted, spatially resolved analysis of molecular species in complex biological tissues. Among the critical steps in MALDI-MSI workflows, matrix deposition significantly influences sensitivity, spatial resolution and reproducibility by affecting crystal morphology and analyte extraction efficiency. While wet deposition techniques, such as manual spray-coating, electrospray deposition and automated systems, have been widely adopted, they often suffer from limitations related to solvent-induced analyte delocalisation. These challenges have driven increasing interest in dry matrix deposition methods, which aim to eliminate or minimise solvent use to enhance spatial fidelity and image quality. This review summarises the main dry deposition strategies used in MALDI-MSI, covering their principles, instrumentation, benefits and limitations. It also discusses recent comparative studies (2023-2025) between wet and dry approaches, examining their impact on analytical performance and the increasing importance of dry deposition in high-resolution spatial omics.