Sheath flow and spray solvents

The first stage of the MSI DPI imaging ion source is DESI (Desorption Electrospray Ionisation): a capillary ejects high-speed charged solvent droplets; these droplets strike the sample surface, desorbing surface molecules into charged microdroplets, which are then dried to form gaseous ions. Within this ‘spray–desorption–ionisation’ sequence, there are two parameters that are most frequently optimised: sheath flow and the composition of the spray solvent. These directly determine how many neutral molecules and ions the MSI DPI front-end can deliver, thereby influencing the supply of ‘raw materials’ for photochemical ionisation in the rear-end.

The sheath flow refers to a layer of auxiliary liquid flow or a gas curtain enveloping the outer side of the central analytical flow path. It acts as a ‘protective shield’: it gathers target ions at the centre of the channel, reduces diffusion losses to the tube walls, and improves transport efficiency from the sampling point to the mass analyser; at the same time, it isolates the system from ambient moisture and contaminants to a certain extent, thereby stabilising ionisation. In MSI DPI, vacuum ultraviolet photochemical ionisation is superimposed following DESI desorption; the design of the sheath flow during the spraying and transport stages directly determines the number of ions that ultimately reach the detector—if the sheath flow is unstable, even the strongest light at the rear end will fail to illuminate a sufficient number of neutral molecules.

The spray solvent acts as the ‘extractant’ in DESI; it consists of a proportionate mixture of water, methanol and acetonitrile, often with a small amount of formic acid or acetic acid added to adjust the pH. It determines two key factors: firstly, which molecules are ‘washed’ off the sample surface (polarity and pH influence extraction efficiency); and secondly, the form in which the desorbed ions exist (e.g. [M+H]⁺ or [M+Na]⁺ adducts). The flow rate is just as critical as the spray needle voltage: too high a flow rate floods the surface, whilst too low a rate results in insufficient desorption; the voltage determines the charge on the droplets and the intensity of desorption.

MSI DPI’s post-photoionisation precisely addresses this shortcoming: even if certain molecules have low ionisation efficiency in the DESI spray, the escaping neutral molecules can still be secondary photoionised by vacuum ultraviolet photons, compensating for polarity discrimination, thereby reducing the sensitivity to spray parameters and making the method more robust. This is also why MSI DPI is more tolerant of solvent systems than simple DESI imaging.

When troubleshooting anomalies in MSI DPI imaging, these two parameters are often the first to be checked: if the signal is generally weak or highly fluctuating, this is usually due to an unstable sheath flow or a blocked spray needle; in such cases, check the gas lines and clean the spray needle first; if unexpected addition peaks or retention time drifts appear in the spectrum, this is often caused by changes in solvent composition or acidity, requiring the solution to be prepared anew and verified; if surface contamination leads to elevated background noise, increase the number of cleaning steps or reduce the spray intensity. MSI DPI is compatible with mainstream mass spectrometers from Agilent, AB SCIEX, Thermo and others; the experience gained in tuning the spray and sheath flow is transferable across different instruments.