Paper spray ionization mass spectrometry method detects Parkinson’s disease biomarkers in less than three minutes

Those of you who regularly cast an eye over the Editor’s Letter in CLI will know that we have been closely following the story of the development of a sebum-based biomarker test to diagnose Parkinson’s disease (PD; Editor’s letters in the Feb/March issues of CLI in 2018 and 2021).

Briefly, the background is that a woman, Joy Milne, with an amazing sense of smell (hyperosmia) had detected a change in her husband’s body aroma over a decade before he was diagnosed with PD. Then, as Joy encountered more people with PD (PwP), she realized that they all had the same musky type of aroma. Determined to take this discovery further, Joy was put in touch with Professor Perdita Barran at the University of Manchester, UK, and they have been working together to identify the compounds involved and to develop a biomarker based test for PD diagnosis. Altered sebum is a wellknown feature of PD, and is linked to mitochondrial dysregulation associated with the disease, so is an ideal but unexplored specimen. Barran and colleagues had previously shown that sebum contains volatile compounds that could be used as biomarkers for PD. Now, however, they have demonstrated a paper spray ionization ion mobility mass spectrometry (PS-IM-MS) technique that allows the direct analysis of sebum from non-invasively collected skin swabs1. The advantages of this technique are that it offers an inexpensive sampling method, minimal sample processing compared to LC-MS, and reveals far larger lipid moieties and provides enhanced separation for analytes with overlapping m/z ratios. Additionally it is fast with analysis from swab to results taking as little as three minutes. This study involved 150 people and the team is now recruiting a larger number of people to see if the method will successfully translate from the research environment into hospital labs. Currently, PD is diagnosed by the patient’s symptoms and medical history and the advantages of a definitive biomarker-based test are obvious.

For now, for method validation purposes, samples from people with confirmed PD are being tested against disease-free controls. However, by the time symptoms appear a significant amount of neurological damage has already occurred and the disease –as detected by Joy in her husband – can begin over a decade earlier. Therefore, for ideal disease management and treatment do we not need to catch people at the very beginning of the pathological process? If the changes are sufficient for Joy to smell, then hopefully the PS-IM-MS method will be able to detect them also. However, that brings us into the realms of screening the asymptomatic population– and that is another discussion.

1 Sarkar D, Sinclair E, Lim SH et al. Paper spray ionization ion mobility mass spectrometry of sebum classifies biomarker classes for the diagnosis of Parkinson’s disease. JACS Au 2022;2(9):2013–2022 (

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Alison Sleigh PhD – Editor