The two hurdles facing traditional DESI: polarity discrimination and ion suppression – how can photoionisation sources overcome them?

Every technology has its ‘inherent limitations’, and the DESI (Desorption Electrospray Ionisation) imaging source is no exception. Whilst it has made a promising start in open-path imaging, it faces two major hurdles: polarity discrimination and ion suppression. New Source’s photoionisation imaging source is specifically designed to tackle these two challenges.

Hurdle 1: Polarity bias – non-polar molecules ‘desorb well but do not ionise well’

DESI relies on charged solvent droplets to desorb and ionise the sample. The problem lies in ionisation preference: the DESI imaging sources commonly used internationally ‘can only image highly polar components’, whilst being less effective for weakly polar and non-polar components. This means that many non-polar molecules—such as lipids, terpenes and flavonoids—are blown off by the spray but do not readily acquire a charge for mass spectrometry, and consequently ‘go missing’ from the image.

The impact on researchers is immediate: in a tissue image, whilst polar metabolites are clearly visible, non-polar molecules appear as a blank space, resulting in a naturally biased spatial distribution. New Source’s MSI DPI highlights this as the very first feature of the product—‘No polarity discrimination (suitable for the ionisation and imaging of non-polar substances)’—achieved precisely through the use of post-ionisation via photochemical ionisation, which incorporates non-polar molecules into the detection pathway.

Hurdle 2: Ion Suppression — Strong Signals Overpower Weak Signals

The second hurdle is ion suppression. When the sample matrix is complex, certain high-abundance ions can ‘snatch’ charge, suppressing the response signal of the analytes of interest; sample purification is therefore required to ensure accurate measurement. DESI also suffers from significant ion suppression in this regard, making it unsuitable for complex samples.

MSI DPI addresses this in two ways: on the one hand, photochemical secondary ionisation broadens the ionisation window, allowing more molecules to acquire their own charges and thereby reducing the overall dominance of a single ion monopolising the charge supply; on the other hand, the product page explicitly states ‘low ion suppression’, meaning complex samples can be analysed directly without the need for tissue washing, solvent washing or chemical derivatisation. This not only eliminates steps but also preserves information that might otherwise be lost during sample purification.

Once these hurdles are overcome: from ‘being able to image’ to ‘daring to analyse samples directly’

Overcoming these two hurdles has brought about not merely improvements in parameters, but a relaxation of the workflow. In the past, when faced with complex samples, researchers had to first consider ‘how to purify them to ensure accurate measurement’; now they can consider ‘what can be observed by loading them directly onto the instrument’. This shift has transformed the imaging source from being ‘suitable only for clean samples’ to ‘daring to handle real samples’.

Behind this lies the logic of a single beam of light: by adding a photoionisation system and a high-efficiency ion transport channel following the DESI spray, and by switching the photoionisation source on and off, high-sensitivity spatial imaging of both polar and non-polar components is achieved. The two hurdles—polarity discrimination and ion suppression—are essentially problems that ‘single ionisation cannot cover’, and the second-stage photoionisation precisely fills this coverage gap.