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Cell Syst. 2016 Apr 27;2(4):225-38. doi: 10.1016/j.cels.2016.03.008. Epub 2016 Apr 27.

Multiplexed Epitope-Based Tissue Imaging for Discovery and Healthcare Applications.

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Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland. Electronic address:


The study of organs and tissues on a molecular level is necessary as we seek an understanding of health and disease. Over the last few years, powerful highly multiplexed epitope-based imaging approaches that rely on the serial imaging of tissues with fluorescently labeled antibodies and the simultaneous analysis using metal-labeled antibodies have emerged. These techniques enable analysis of dozens of epitopes in thousands of cells in a single experiment providing a systems level view of normal and disease processes at the single-cell level with spatial resolution in tissues. In this Review, I discuss, first, the highly multiplexed epitope-based imaging approaches and the generated data. Second, I describe challenges that must be overcome to implement these imaging methods from bench to bedside, including issues with tissue processing and analyses of the large amounts of data generated. Third, I discuss how these methods can be integrated with readouts of genome, transcriptome, metabolome, and live cell information, and fourth, the novel applications possible in tissue biology, drug development, and biomarker discovery. I anticipate that highly multiplexed epitope-based imaging approaches will broadly complement existing imaging methods and will become a cornerstone of tissue biology and biomedical research and of precision medical applications.


Tissue systems biology; clinical pathology; computational biology; imaging mass cytometry; multiplexed imaging; multiplexed ion beam imaging; precision medicine; quantitative pathology; serial immunofluorescence microscopy; single-cell analysis

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