DESI uses charged droplets to desorb surface molecules and sprays no organic matrix, so there are no MALDI-style matrix background peaks. But real samples (tissue, blood, plants) are rich in endogenous lipids, salts and metabolites, which are desorbed together, forming a complex background and possibly suppressing the target analyte.
In addition, buffer or saline residues on the sample surface can also change spray ionization efficiency, causing signal drift. So 'interference' mainly comes from the sample itself and its preparation, not from an externally added matrix.
The first step to reduce interference is sample preparation: gently wash surface salts and buffer residues with a suitable solvent, control section storage conditions and avoid contamination. The spray solvent composition of DESI (water/organic phase ratio, additives) also directly affects desorption and ionization selectivity.
By adjusting spray solvent polarity, pH and flow rate, the response of the target analyte can be enhanced and endogenous co-eluents suppressed. For complex matrices such as blood and urine, a dedicated solvent recipe and cleaning workflow often need to be established.
On the analysis side, mass spectrometry imaging software (such as MSCL, SCiLS Lab, Cardinal) can be used for normalization, background subtraction and multivariate statistics, to separate target signals from endogenous background. For highly overlapping peaks, high-resolution accurate mass or tandem mass spectrometry (MS/MS) can help with identification.
But data processing can only 'restore' signals, not eliminate strong suppression out of thin air. If endogenous interference is too strong and the low-mass region is submerged, one should consider switching sources fundamentally.
When the sample background is extremely complex and the target is a low-mass small molecule, DESI's endogenous interference significantly drags down sensitivity. In this case one can switch to Neo-Source LDPI—laser desorption plus photoionization, completely matrix-free, low background above m/z≥70, reducing interference at the source.
DPI, on the other hand, stacks photoionization secondary ionization on top of desorption electrospray, with sensitivity 1–4 orders of magnitude higher than DESI and no polarity bias, and can newly detect over a hundred secondary metabolites in both positive and negative ion modes, suiting strong-interference scenarios of complex biological samples.
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).