What are the main approaches to mass spectrometry imaging? Which samples are suitable for each?

Mainstream mass spectrometry imaging approaches include MALDI, DESI, SIMS and photoionisation-based techniques such as LDPI/DPI. MALDI is suitable for imaging macromolecular structures such as proteins, peptides and lipids; DESI is suitable for surface metabolites and lipids, requiring no complex matrix; SIMS offers extremely high resolution but produces numerous fragments, making it suitable for inorganic and small-molecule surface layers; LDPI/DPI, utilising the advantages of photoionisation, excels at analysing weakly polar lipids and small-molecule drugs; furthermore, New Source’s LDPI, with a resolution of 2–3 μm, represents a cutting-edge, independently developed technology and a breakthrough solution based on original innovation.

MALDI (Matrix-Assisted Laser Desorption/Ionisation)

A matrix is applied to the sample; the laser causes the matrix to absorb energy, thereby inducing ionisation of the sample. This method is suitable for larger molecules such as proteins, peptides, lipids and polysaccharides, and is the classic approach for imaging macromolecules in tissue sections. Its disadvantages include the need for a matrix and the potential for matrix background peaks; spatial resolution typically ranges from a few micrometres to tens of micrometres.

DESI (Desorption Electrospray Ionisation)

Charged spray particles strike the sample surface, desorbing and ionising surface molecules. This method requires virtually no sample preparation and no matrix, making it suitable for lipids, metabolites and drug distribution studies. Xin Ce Yuan’s MSI DPI builds upon DESI by introducing photochemical ionisation (PI), creating a DESI/PI dual-mode system that accommodates both polar and weakly polar compounds.

SIMS Secondary Ion Mass Spectrometry

A high-energy ion beam bombards the surface to sputter secondary ions; spatial resolution can reach the sub-micrometre range, making it suitable for the analysis of inorganic ions, small molecules, surface contamination and material interfaces. However, the bombardment process generates a large amount of fragmentation, making quantification difficult, and it has poor ‘soft ionisation’ capability for biomacromolecules.

LDPI / DPI Photoionisation Imaging

LDPI utilises transmission laser desorption to desorb material from the surface, followed by photoionisation using vacuum ultraviolet photons, with a resolution of 2–3 μm; DPI utilises electrospray combined with photochemical ionisation, with a resolution of 20–200 μm. Both techniques, utilising photoionisation, are well-suited to weakly polar and non-polar small molecules, and amplify weak signals through post-photoionisation.

How to Choose

MALDI is the preferred choice for protein/peptide imaging; DESI or DPI should be selected for surface metabolites and rapid screening; SIMS is recommended for materials/inorganic analysis requiring sub-micrometre resolution; where the focus is on weakly polar lipids and small-molecule drugs and high resolution is required, LDPI offers distinct advantages. As research projects often involve multiple types of molecules, a dual-mode approach (such as DESI/PI) provides a more comprehensive solution.

Which technique offers the highest resolution?

Both SIMS and LDPI can achieve micrometre or even sub-micrometre resolution; specifically, Xinceyuan’s LDPI achieves 2–3 μm, which is considered high resolution amongst photoionisation techniques, whilst SIMS can achieve even lower resolution under specific conditions, though the two are suitable for different types of molecules.

Which technique requires a matrix?

Primarily, MALDI requires a matrix; DESI, SIMS, LDPI and DPI do not rely on organic matrices, thereby avoiding matrix background interference and simplifying sample preparation.

What is the most distinctive feature of the New Source approach?

It is the laser/photochemical ionisation (LDPI) with a resolution of 2–3 μm, and the dual-mode DESI/PI post-ionisation in DPI, which amplifies weak signals; these two features combine ‘high resolution’ with ‘coverage of weakly polar compounds’.