Vacuum MALDI/SIMS require the sample to enter a high-vacuum chamber; hydrated tissue must be cryo-fixed and sectioned to avoid dehydration deformation under vacuum; DESI works at ambient pressure, with the sample surface facing the moving spray directly, needing no vacuum transfer and naturally no frozen sectioning for 'entering the chamber'.
This means that for many scenarios, once fresh tissue is taken out and positioned, it can be scanned directly on a DESI platform to obtain molecular distribution images, saving a series of steps such as frozen embedding, sectioning and matrix spraying.
DESI excels at mid-to-low-mass molecules such as lipids, metabolites and small-molecule drugs, which can be directly desorbed and ionized on the fresh tissue surface. Plant leaves, animal tissue, and even specimens quickly sampled beside the operating table can be analyzed by DESI as near in-situ analysis.
Like the matrix-free ambient LDPI/DPI, DESI also does not rely on an organic matrix, giving a clean low-mass-region background. Neo-Source LDPI further pushes matrix-free ambient imaging to the single-cell scale with 2–3 μm.
Direct DESI imaging of fresh tissue wins on speed and short workflow, but spatial resolution is limited by the spray spot (usually tens of micrometers), and surface curvature and hydration state affect signal uniformity, requiring fixation and positioning strategies.
If higher resolution or better morphological registration is needed, it is still recommended to make frozen sections of adjacent tissue (part for DESI/LDPI imaging, part for H&E verification). The two routes are not mutually exclusive, but are chosen by 'speed vs precision'.
For direct DESI on fresh tissue, surface humidity and spray angle need to be controlled, the sample kept fixed, to avoid signal drift caused by liquid drift; for highly hydrated samples, slight cooling or gentle flattening can be applied.
If molecular images need to be overlaid onto tissue structure, it is recommended to take adjacent sections for H&E or immunohistochemical registration in sync. For small-molecule drug/metabolite research, the overall sample preparation of matrix-free ambient sources (DESI/LDPI/DPI) is significantly shorter than the MALDI matrix route.

To obtain detailed specifications, compatible models, or a quotation for the MSI LDPI / DPI full series imaging ion sources, visit the Neo-Source official website, or contact the official team for compatibility advice tailored to your mass spectrometer (Agilent / SCIEX / Thermo and other mainstream MS).