Multiplexed ion beam imaging (MIBI) of human breast tumors

By Michael Angelo, Sean Bendall, R. Finck, M. Hale, C. Hitzman, A. Borowsky, R. Levenson, J. Lowe, Scot D. Liu, Shuchun Zhao and 2 more. Nature Medicine, 2014

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Immunohistochemistry (IHC) is a tool for visualizing protein expression that is employed as part of the diagnostic workup for the majority of solid tissue malignancies. Existing IHC methods use antibodies tagged with fluorophores or enzyme reporters that generate colored pigments. Because these reporters exhibit spectral and spatial overlap when used simultaneously, multiplexed IHC is not routinely used in clinical settings. We have developed a method that uses secondary ion mass spectrometry to image antibodies tagged with isotopically pure elemental metal reporters. Multiplexed ion beam imaging (MIBI) is capable of analyzing up to 100 targets simultaneously over a five-log dynamic range. Here, we used MIBI to analyze formalin-fixed, paraffin-embedded human breast tumor tissue sections stained with ten labels simultaneously. The resulting data suggest that MIBI can provide new insights into disease pathogenesis that will be valuable for basic research, drug discovery and clinical diagnostics.

Subfields: Molecular Biology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/ddbea97e965d384436d396bb77abe17abd8fa317

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Citations in the corpus

Deep Learning for Imaging Flow Cytometry: (2016, background): “Furthermore, given that multi-spectral 273 methods are advancing rapidly, imaging mass spectrometry is allowing dozens of labeled 274 channels to be acquired [23,24].”
Intratumor heterogeneity: the Rosetta stone of therapy resistance (2020, background): “Phenotypic heterogeneity can also be assessed by high multiplexing capacity of CytometryTime-of-Flight (CyTOF) (Spitzer and Nolan, 2016), multiplexed ion beam imaging (MIBI) (Angelo et al., 2014), and cyclic immunofluorescence (cycIF) (Lin et al., 2015) techniques that allow for the quantification o”
Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020, background): “Prior to dissociation, portions of tumors were fresh frozen and formalin-fixed for ST (Salmén et al., 2018b; Ståhl et al., 2016) and MIBI (Angelo et al., 2014), respectively (Figure 1A).”
Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes (2018, methodology): “159 Multiplexing antibodies and stains makes it possible to discriminate among proliferating, quiescent and dying 160 cells, identify tumor and stroma, and collect immuno-phenotypes.(19,27,28) Use of phospho-specific antibodies and 161”
The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution (2020, neutral): “Recent advances in single-cell and multiplexed spatial analysis of tissue allow us to interrogate this complexity at unprecedented resolution (Angelo et al., 2014; Buenrostro et al., 2015; Chen et al., 2016a; Chen et al., 2016b; Du et al., 2019; Gaublomme et al., 2019; Gierahn et al., 2017; Giesen e”
Sensitive detection of rare disease-associated cell subsets via representation learning (2016, background): “It is becoming routine to measure thousands of DNA, RNA 3 and dozens of protein 4 species in thousands of single cells, optionally including their spatial context 5–7 .”