Emanuelle Claude (Presenter)
Waters Corporation
Authorship: Emmanuelle Claude, Emrys Jones, Philippa Hart Mark Towers
Waters Corporation , Wilmslow , UK
| Short Abstract Mass spectrometry imaging (MSI) is now increasingly used for clinical research applications due to significant technological improvements that have made the technique more accessible. MALDI, initially introduced by Caprioli et al1, is the dominant MSI technique used today, due to the ability of MALDI to analyse proteins and also its widespread commercial availability. In the last few years, several alternative ambient ionization techniques have been developed that can ionize clinically important molecules such as lipids directly from tissue. One of these techniques, desorption electrospray ionization (DESI), requires minimum sample preparation and is therefore more compatible within a clinical research environment Here we compare and contrast these two imaging techniques which can be operated on an oa-QTOF mass spectrometer. |
Long Abstract
Mass spectrometry imaging (MSI) is now increasingly used for clinical research applications due to significant technological improvements that have made the technique more accessible. Matrix-assisted laser desorption/ionization (MALDI), initially introduced by Caprioli et al1, is the dominant MSI technique used today, due to the ability of MALDI to analyse intact proteins directly from tissue. Furthermore MALDI is widely available and has been commercially developed by a number of vendors.
In the last few years, several alternative ambient ionization techniques have been developed that can ionize clinically important molecules such as lipids directly from tissue. One of these techniques is desorption electrospray ionization (DESI). DESI, a surface analysis technique incorporating an electrospray probe, can be utilized as a spatially resolved imaging technique by rastering a surface under the spray using a high precision XY stage. As the electrospray droplets impact upon a surface, chemical constituents are desorbed and transferred into the atmospheric inlet of the mass spectrometer source. Ionization occurs due to the charge imparted onto the droplets. No modification to the sample such as matrix addition is necessary and therefore minimum sample preparation is required to run a DESI imaging experiment, making this technique more compatible within a clinical research environment
Here we compare and contrast MALDI and DESI imaging techniques which are operated on an oA-QTOF mass spectrometers, such as the SYNAPT G2-Si and Xevo-G2-XS QTof.
The tissue sections analyzed were mainly frozen tissue sections, however FFPE tissue sections which are more common in clinical settings can also be used for MS imaging.
Experiments were carried out by MALDI imaging on tissue samples including rodent brain, xenograph and clinical human tissue sections. Matrix solution was sprayed automatically using a commercial SunCollect nebulizing spray device, making the sample preparation step more reproducible than manual spraying. In some examples, such as FFPE tissue sections (including from frozen samples), a trypsin solution was sprayed prior to the matrix application, to cleave proteins into tryptic peptides.
Consecutive or similar tissue sections were also analysed by DESI imaging. However in these experiments, no sample preparation step was required. Solvent solutions mainly used for the desorption and ionisation step were a mixture of Methanol-Water, which proved ideal for lipids and/or small molecule metabolite detection. By managing solvent and gas flow rates appropriately, in combination with the optimised voltages, the DESI technique resulted in negligible destruction of the tissue surface and therefore the same tissue sample can be histologically stained. In this case the molecular distribution was compared with the tissue's microscopic structure obtained from the H&E stained image.
References & Acknowledgements:
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