Laser energy is first absorbed by the matrix; the matrix rapidly vaporizes and desorbs the analyte into the gas phase together, while proton transfer occurs to charge the analyte. Without a suitable matrix, the laser hitting the tissue directly can hardly achieve effective ionization.
The chemical structure of the matrix determines what charge it tends to carry and in which mass region it produces background peaks; therefore choosing the wrong matrix damages both signal and background. Uniform spraying is another key point, as uneven crystallization causes imaging artifacts.
DHB (2,5-dihydroxybenzoic acid) is a classic matrix for analyzing larger molecules such as proteins and peptides (m/z above several thousand), giving robust signals for these macromolecules in positive-ion mode, with fine-needle-like, relatively uniform crystallization.
Its biggest shortcoming is the dense matrix peaks it produces in the low-mass region (m/z<700), interfering with drugs and metabolites; therefore DHB is not ideal for small-molecule imaging and one often needs to switch to a matrix-free source (LDPI/DPI/DESI).
CHCA (α-cyano-4-hydroxycinnamic acid) is commonly used for peptides, small proteins and some medium-mass molecules; it crystallizes into micrometer-scale dots and offers high sensitivity for many protein/peptide analyses, making it a common choice for proteomics MALDI.
Similar to DHB, CHCA also has matrix background in the low-mass region, and uneven dot-like crystallization can affect imaging quality. When selecting, it is common to first run standard tests to confirm that the target analyte gives the optimal signal under the chosen matrix.
A practical matrix-selection workflow: first pre-screen by the target molecule's mass range (macromolecules → DHB/CHCA, small molecules → be cautious or switch sources) → spray standards to verify signal and crystallization → optimize spraying parameters (concentration, temperature, number of layers).
If the research subject is small-molecule drugs/metabolites, it is strongly recommended to skip the matrix hassle and directly adopt matrix-free ambient sources: Neo-Source LDPI (low background above m/z≥70, 2–3 μm) and DPI (20–200 μm, sensitivity 1–4 orders of magnitude higher than DESI) eliminate matrix interference at the source.
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).