Multimodal Ion Beam Imaging to Correlate Elements and Metabolites at the Micron Scale Using Water Cluster Secondary Ion Mass Spectrometry and MeV Ion Beam Analysis.

Multiomics imaging at or below the single cell level is highly sought after for correlating the location of metal containing drugs, nanoparticles, or bioaccumulated metals with host metabolites and lipids. Secondary ion mass spectrometry (SIMS) is a technique that can image lipids and metabolites at high spatial resolution (∼1 μm), especially water cluster SIMS. Similarly, X-ray mapping techniques such as particle induced X-ray emission (PIXE) can image elements at submicron spatial resolution in tissues. Here we developed a workflow for SIMS followed by X-ray elemental mapping, performed on the same section of tissue. To enable compatibility with X-ray spectrometry, samples were mounted on a thin polymer film, which proved challenging for SIMS due to charge accumulation on the sample surface. Various sample preparation strategies, including carbon coating and metallic grids, were tested to overcome this issue. Multimodal imaging using SIMS and ion beam analysis (IBA) was then successfully performed on a porcine skin section. By way of example, we show how SIMS-IBA can be applied to image the different regions of a hair follicle to colocate elements, metals, and lipids using sequential elemental and molecular mapping, without any delocalization or loss by the preceding measurement.