After the first laser (or matrix-absorbing laser) completes desorption/ablation, sample molecules enter the gas-phase plume mostly as neutrals; the second laser excites neutral molecules to an ionized state or directly ejects electrons through resonant or multi-photon absorption, forming detectable ions. The two steps are separated in time and space, facilitating separate parameter tuning.
The wavelength, energy density, and delay of the second laser relative to the primary event directly determine ionization efficiency and fragmentation. Too strong introduces fragments and background; too weak gives insufficient gain, so there is an optimal window for specific molecular classes.
MALDI-2 overlays laser-induced post-ionization on top of conventional MALDI desorption: the matrix first absorbs the laser to complete desorption, and after neutral molecules enter the plume they are post-ionized by the second laser. This combination expands weak-signal molecular coverage without changing pixel resolution.
Because it still relies on the matrix, MALDI-2 retains sample preparation such as matrix spraying; its gain is mainly reflected in neutral molecules such as lipids and metabolites that have low ion yield under conventional MALDI.
Neo-Source LDPI works in a matrix-free, ambient environment through laser-induced photoionization, eliminating matrix spraying; DPI further adopts a dual photoionization structure, with higher sensitivity for polar molecules than DESI. Both share the idea of a second light/photochemical step improving ionization but omit the matrix desorption step.
This extends laser-induced post-ionization from a gain module of MALDI to the core principle of an independent matrix-free imaging source, suitable for imaging scenarios requiring matrix-free, interference-free, in-situ ambient conditions.
When adopting laser-induced post-ionization, the timing of the two lasers, wavelength matching, and energy ratio must be systematically optimized, with attention to background suppression. For existing MALDI platforms, the MALDI-2 module has low retrofit cost; for building a new matrix-free ambient imaging line, LDPI/DPI is more direct.
From molecular applicability, neutral, low-polarity, or difficult-to-ionize molecules benefit most from this mechanism; strongly polar easily ionized molecules already perform well under conventional ionization, with relatively limited gain.
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).