MALDI forms pixels by irradiating the sample surface point-by-point with a laser, inherently possessing spatial resolution and serving as the classic source for tissue imaging. ESI originally ionizes a solution continuously—the spray is fixed and the sample does not move—so it has no spatial resolution mechanism.
To make ESI image, it must be given a scanning mechanism and a surface desorption step, namely DESI (Desorption Electrospray Ionization)—using a moving spray to desorb the sample surface. Thus "ESI imaging" in practice usually refers to ESI-derived ambient sources such as DESI.
MALDI targets solid tissue sections, using matrix-assisted soft ionization of macromolecules such as proteins, peptides, and sugars, with the low-mass region suffering matrix interference. ESI/DESI targets surfaces or liquid phases, excelling at mid-to-low-mass molecules such as lipids, metabolites, and small-molecule drugs—ambient and matrix-free with low background.
Their molecular coverage is complementary: MALDI sees macromolecules, DESI (ESI-derived) sees small molecules. Neo-Source LDPI achieves matrix-free imaging at 2–3 µm via laser desorption plus photoionization, offering a new small-molecule single-cell imaging path that runs parallel to MALDI's macromolecule route.
MALDI requires matrix spraying and vacuum, with longer preprocessing; DESI/ESI-derived sources are ambient and matrix-free—sections are positioned and the instrument is ready, making the workflow shorter. But ESI's native LC-MS quantification (non-imaging) remains the mainstay for bulk-sample overall quantification.
Distinguish between "ESI for LC-MS quantification" and "ESI-derived source for imaging": the former measures overall concentration, the latter shows spatial distribution; the two are often used together in drug-metabolism research (LC-MS gives exposure, MSI gives localization).
If the target is spatial distribution of tissue macromolecules (proteins/peptides) → MALDI; if the target is spatial distribution of small-molecule metabolites/drugs and ambient matrix-free is required → DESI or LDPI/DPI; if only overall concentration quantification is needed → ESI-LC-MS.
The three are not substitutes: use MALDI for proteins, LDPI/DESI for small molecules, and ESI-LC-MS for overall quantification, then register with H&E to form a complete molecular pathology evidence chain.
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).