Enhancement of biological mass spectrometry by using separations based on changes in ion mobility (FAIMS and DMS)

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.

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Spatial Metabolomics of the Human Kidney Using MALDI Trapped Ion Mobility Imaging Mass Spectrometry

10.26434/chemrxiv.12118644.v2 ◽

2020 ◽

Author(s):

Elizabeth Neumann ◽

Lukasz Migas ◽

Jamie L. Allen ◽

Richard Caprioli ◽

Raf Van de Plas ◽

...

Keyword(s):

Mass Spectrometry ◽

Ion Mobility ◽

Imaging Mass Spectrometry ◽

Structural Complexity ◽

Human Kidney ◽

Resolving Power ◽

Mobility Separation ◽

Trapped Ion ◽

Mobility Data ◽

Ion Mobility Separation

<div> <div> <p>Small metabolites are essential for normal and diseased biological function but are difficult to study because of their inherent structural complexity. MALDI imaging mass spectrometry (IMS) of small metabolites is particularly challenging as MALDI matrix clusters are often isobaric with metabolite ions, requiring high resolving power instrumentation or derivatization to circumvent this issue. An alternative to this is to perform ion mobility separation before ion detection, enabling the visualization of metabolites without the interference of matrix ions. Here, we use MALDI timsTOF IMS to image small metabolites at high spatial resolution within the human kidney. Through this, we have found metabolites, such as arginic acid, acetylcarnitine, and choline that localize to the cortex, medulla, and renal pelvis, respectively. We have also demonstrated that trapped ion mobility spectrometry (TIMS) can resolve matrix peaks from metabolite signal and separate both isobaric and isomeric metabolites with different localizations within the kidney. The added ion mobility data dimension dramatically increased the peak capacity for molecular imaging experiments. Future work will involve further exploring the small metabolite profiles of human kidneys as a function of age, gender, and ethnicity.</p></div></div>

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