Metabolites, lipids and the vast majority of small-molecule drugs (mostly m/z below 1000) are best suited to matrix-free ambient sources (DESI, LDPI, DPI). LDPI presents small molecules with a low background above m/z≥70 and matrix-free; DPI has sensitivity 1–4 orders of magnitude higher than DESI, and in negative/positive ion modes can newly detect over a hundred secondary metabolites.
In plant and herbal-medicine imaging, DPI has demonstrated sensitive detection of theanine (signal increased 14.5×), caffeine (61×), flavonoids, terpenes, etc., showing that small molecules are among the most mature application ranges of MSI.
Peptides, sugars and some medium-mass molecules are well presented by MALDI via matrix-assisted soft ionization, and can also be partly covered by ESI-derived sources (DESI). MALDI gives robust signals in this high-mass region.
For projects that need to see both peptides and small molecules, MALDI (peptides/proteins) and LDPI/DESI (small molecules) are often combined and registered to the same tissue.
Large molecules such as proteins, peptides and nucleic acids (m/z thousands to tens of thousands) are mainly covered by MALDI and SIMS, among which MALDI is the most mature for intact protein/peptide imaging and is the main force for spatializing tissue proteomics.
SIMS can also measure large molecules but is a hard-ionization, easily fragmenting approach; ambient matrix-free sources (LDPI/DPI/DESI) lean toward small and medium molecules and are weak at imaging intact large proteins. Therefore 'wanting to see proteins' essentially points to MALDI.
TOF-SIMS can also detect elements, inorganic ions and surface chemistry, a unique means for materials and biomineralization research with resolution down to the nanometer scale. This is the exclusive capability of SIMS compared with other sources.
Summary: small molecules / metabolites / drugs / lipids → DESI/LDPI/DPI; peptides/proteins → MALDI; nanometer-scale elements/lipids → SIMS. Choosing the source by target molecule is the first step in MSI method design.
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).