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Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking

Nature Nanotechnology volume 12, pages 274–281 (2017)Cite this article

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Abstract

Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in whole blood is critical to unravelling the complex and dynamic properties of these potential clinical markers. This task is challenging because these cells are present at parts per billion levels among normal blood cells. Here we report a new nanoparticle-enabled method for CTC characterization, called magnetic ranking cytometry, which profiles CTCs on the basis of their surface expression phenotype. We achieve this using a microfluidic chip that successfully processes whole blood samples. The approach classifies CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers, which is read out using magnetic nanoparticles. We deploy this new technique to reveal the dynamic phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth and aggressiveness. We also test magnetic ranking cytometry using blood samples collected from cancer patients.

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Figure 1: The MagRC approach to profiling rare cells.
Figure 2: Modelling of cell capture in the MagRC device.
Figure 3: Profiling protein surface expression using MagRC.
Figure 4: MagRC applied to rare cells in whole blood.
Figure 5: MagRC enables profiling of CTCs in cancer xenograft models and patient samples.

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Acknowledgements

The authors acknowledge generous support from the Canadian Institutes of Health Research (Emerging Team grant, POP grant), the Ontario Research Fund (ORF Research Excellence grant), the Canadian Cancer Society Research Institute (Innovation grant) and the Connaught Foundation. We also acknowledge all of the patients and healthy donors who donated specimens to our studies.

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Authors and Affiliations

  1. Department of Electrical and Computer Engineering, Faculty of Engineering, University of Toronto, Toronto, M5S 3G4, Ontario, Canada

    Mahla Poudineh & Edward H. Sargent

  2. Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, M5S 3M2, Ontario, Canada

    Peter M. Aldridge, Brenda J. Green, Leyla Kermanshah & Shana O. Kelley

  3. Department of Pharmaceutical Science, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S 3M2, Ontario, Canada

    Sharif Ahmed, Vivian Nguyen, Carmen Tu, Reza M. Mohamadi & Shana O. Kelley

  4. Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, M4N 3M5, Ontario, Canada

    Robert K. Nam

  5. Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, M5G 2M9, Ontario, Canada

    Aaron Hansen, Srikala S. Sridhar, Antonio Finelli, Neil E. Fleshner & Anthony M. Joshua

  6. Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, M5S 1A8, Ontario, Canada

    Shana O. Kelley

Authors
  1. Mahla Poudineh
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  16. Shana O. Kelley
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Contributions

M.P., P.M.A., S.A., B.J.G., L.K., V.N., C.T., R.M.M., S.O.K. and E.H.S. conceived and designed the experiments. M.P., P.M.A., S.A. B.J.G., L.K., V.N., C.T. and R.M.M. performed the experiments and analysed the data. R.K.N., A.H., S.S.S., A.F., N.E.F. and A.M.J. contributed clinical expertise and clinical specimens. All authors discussed the results and contributed to the preparation and editing of the manuscript.

Corresponding authors

Correspondence to Edward H. Sargent or Shana O. Kelley.

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The authors declare no competing financial interests.

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Poudineh, M., Aldridge, P., Ahmed, S. et al. Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking. Nature Nanotech 12, 274–281 (2017). https://doi.org/10.1038/nnano.2016.239

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