Joel D Keelor oral presentation (PB1-Mon2-1-6)
Combining SIMS and MALDI for Multimodal Imaging Mass Spectrometry
Maastricht MultiModal Molecular Imaging Institute (M4I), Universitseitssingel 50, 6229 ER Maastricht, Netherlands
The imaging mass spectrometry field now embraces a diversity of ion source techniques, with the chief examples including classic primary ion beam-based probes used in secondary ion mass spectrometry (SIMS), solvent-based desorption electrospray ionization (DESI), and matrix-assisted laser desorption ionization (MALDI) . Of course, each MS imaging source offers unique advantages, but the common source attributes that remain most desirable are spatial resolution, analysis speed/sensitivity, and complete analyte coverage. SIMS has evolved to encompass “softer” clustered ion sources, such as C60+ and the argon gas cluster ion beam (GCIB), which have expanded SIMS applications beyond depth-analysis of inorganic thin-film materials to the chemical mapping of biological tissue and even single cells . For such applications, SIMS is the only method capable of reaching the sub-micron resolutions required to correlate chemical information to individual cells within tissue. Still, MS imaging of bio-samples continues to be the domain of MALDI, where SIMS cannot currently compete with the achievable dynamic range of MALDI-MS for the detection of intact macromolecules. Yet as MALDI technology is approaching the upper limit of SIMS spatial resolutions (~1 µm), and SIMS methods have begun incorporating MALDI matrices for selective signal enhancement, these two techniques have grown evermore compatible .
In this work we present recent results acquired using a stigmatic ion imaging mass spectrometer incorporating both a C60+ cluster SIMS ion beam (Ionoptika Ltd, Southampton, United Kingdom) and a UV-MALDI source (Spectra-Physics, Santa Clara, CA, United States) for full-range multimodal imaging analysis. This dual source configuration was adapted to a BioTRIFT mass analyzer (Physical Electronics, Chanhassen, MN, United States) with a TimePixII detector for stigmatic imaging. Altogether, this system affords greater analysis speed using MALDI for large area substrates together with the sub-micron spatial resolution and 3D depth-profiling achievable with SIMS, including the first report of SIMS stigmatic imaging of single cells whereby spatial resolution is independent of the focused spot size of the beam. An overview of the general system performance will be demonstrated, comparing and contrasting MALDI and SIMS imaging capabilities for identical tissue samples, and a smart image registration algorithm for scaling images to higher resolution is briefly showcased.
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