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Compositional Mapping of the Surface and Interior of Mammalian Cells at Submicrometer Resolution



Christopher Szakal, Kedar Narayan, Jing Fu, Jonathan A. Lefman, Sriram Subramaniam


We present progress towards imaging of chemical species within intact mammalian cells using secondary ion mass spectrometry, with simultaneous mapping of subcellular elemental and molecular species along with intrinsic membrane-specific cellular markers. Results from imaging of both the cell surface and cell interior exposed by site-specific focused ion beam milling demonstrate that in-plane resolutions of approximately 400 nm can be achieved. The results from mapping cell surface phosphatidylcholine and several other molecular ions present in the cells establish that spatially-resolved chemical signatures of individual cells can be derived from novel multivariate analysis and classification of the molecular images obtained at different m/z ratios. The methods we present here for specimen preparation and chemical imaging of cell interiors provide the foundation for obtaining 3D molecular maps of unstained mammalian cells, with particular relevance for probing the subcellular distribution of small molecules, such as drugs and metabolites.
Analytical Chemistry


single cell imaging, hela cells, imaging mass spectrometry, SIMS, submicrometer, FIB


Szakal, C. , Narayan, K. , Fu, J. , Lefman, J. and Subramaniam, S. (2011), Compositional Mapping of the Surface and Interior of Mammalian Cells at Submicrometer Resolution, Analytical Chemistry, [online],, (Accessed April 20, 2024)
Created January 26, 2011, Updated October 13, 2022