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Multiplexed ion beam imaging (MIBI) is a novel approach to immunohistochemistry (IHC) that uses secondary ion mass spectrometry (SIMS) and antibodies labeled with elemental mass tags to visualize dozens of proteins simultaneously in a single tissue section. MIBI is compatible with standard formalin-fixed, paraffin-embedded (FFPE) tissue specimens, the most common sample type in clinical repositories worldwide, and can achieve single molecule sensitivity across a five log dynamic range at resolutions equivalent to brightfield microscopy. In recent work, MIBI was validated for imaging breast tumor tissue sections stained with clinically relevant metal-conjugated antibodies via side-by-side comparison with an FDA-approved quantitative image analysis platform. Since that time, my lab has validated over sixty antibodies and has constructed a 45-plex MIBI panel for characterizing phenotypic and epigenetic features of epithelial, stromal, and infiltrating immune cells in clinical breast tumor biopsies. Analogous approaches with metal conjugated oligonucleotides have also been used for multiplexed DNA and RNA ISH. Finally, to permit broader use of this method, we have designed and constructed novel instrumentation optimized for MIBI that is capable of super resolution imaging and one hundred fold faster sample throughput. Taken together, these tools are being used by lab to comprehensively enumerate immune cell populations in normal and neoplastic solid tissues, to develop clinical classifiers for predicting disease progression in pre-invasive cancer lesions, and to discover epigenetic drivers of epithelial to mesenchymal transition.