Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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


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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others


  1. Chaffer, C. L. & Weinberg, R. A. A perspective on cancer cell metastasis. Science 331, 1559–1564 (2011).

    Article  CAS  Google Scholar 

  2. Plaks, V., Koopman, C. D. & Werb, Z. Circulating tumor cells. Science 341, 1186–1188 (2013).

    Article  CAS  Google Scholar 

  3. Alix-Panabières, C. & Pantel, K. Challenges in circulating tumour cell research. Nat. Rev. Cancer 14, 623–631 (2014).

    Article  Google Scholar 

  4. Lang, J. M., Casavant, B. P. & Beebe, D. J. Circulating tumor cells: getting more from less. Sci. Transl. Med. 4, 141ps13 (2012).

    Article  Google Scholar 

  5. Green, B. J. et al. Beyond the capture of circulating tumor cells: next-generation devices and materials. Angew. Chem. Int. Ed. 55, 1252–1265 (2016).

    Article  CAS  Google Scholar 

  6. Hu, X. et al. Marker-specific sorting of rare cells using dielectrophoresis. Proc. Natl Acad. Sci. USA 102, 15757–15761 (2005).

    Article  CAS  Google Scholar 

  7. Nagrath, S. et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235–1239 (2007).

    Article  CAS  Google Scholar 

  8. Adams, A. et al. Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor. J. Am. Chem. Soc. 130, 8633–8641 (2008).

    Article  CAS  Google Scholar 

  9. Talasaz, A. H. et al. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc. Natl Acad. Sci. USA 106, 3970–3975 (2009).

    Article  CAS  Google Scholar 

  10. Stott, S. L. et al. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc. Natl Acad. Sci. USA 107, 18392–18397 (2010).

    Article  CAS  Google Scholar 

  11. Wang, S. et al. Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. Angew. Chem. Int. Ed. 50, 3084–3088 (2011).

    Article  CAS  Google Scholar 

  12. Schiro, P. G. et al. Sensitive and high-throughput isolation of rare cells from peripheral blood with ensemble-decision aliquot ranking. Angew. Chem. Int. Ed. 51, 4618–4622 (2012).

    Article  CAS  Google Scholar 

  13. Zhao, W. et al. Bioinspired multivalent DNA network for capture and release of cells. Proc. Natl Acad. Sci. USA 109, 19626–19631 (2012).

    Article  CAS  Google Scholar 

  14. Ozkumur, E. et al. Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci. Transl. Med. 5, 179ra47 (2013).

    Article  Google Scholar 

  15. Reátegui, E. et al. Tunable nanostructured coating for the capture and selective release of viable circulating tumor cells. Adv. Mater. 27, 1593–1599 (2015).

    Article  Google Scholar 

  16. Mittal, S., Wong, I. Y., Yanik, A. A., Deen, W. M. & Toner, M. Discontinuous nanoporous membranes reduce non-specific fouling for immunoaffinity cell capture. Small 9, 4207–4214 (2013).

    Article  CAS  Google Scholar 

  17. Schneider, J. et al. A novel 3D integrated platform for the high-resolution study of cell migration plasticity. Macromol. Biosci. 13, 973–983 (2013).

    Article  CAS  Google Scholar 

  18. Mohamadi, R. M. et al. Nanoparticle-mediated binning and profiling of heterogeneous circulating tumor cell subpopulations. Angew. Chem. Int. Ed. 54, 139–143 (2015).

    Article  CAS  Google Scholar 

  19. Ferguson, B. S. et al. Genetic analysis of H1N1 influenza virus from throat swab samples in a microfluidic system for point-of-care diagnostics. J. Am. Chem. Soc. 133, 9129–9135 (2011).

    Article  CAS  Google Scholar 

  20. Chen, P., Huang, Y.-Y., Hoshino, K. & Zhang, J. X. J. Microscale magnetic field modulation for enhanced capture and distribution of rare circulating tumor cells. Sci. Rep. 5, 8745 (2015).

    Article  CAS  Google Scholar 

  21. Santisteban, M. et al. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 69, 2887–2895 (2009).

    Article  CAS  Google Scholar 

  22. Yu, M. et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339, 580–584 (2013).

    Article  CAS  Google Scholar 

  23. Jaye, D. L., Bray, R. A., Gebel, H. M., Harris, W. A. C. & Waller, E. K. Translational applications of flow cytometry in clinical practice. J. Immunol. 188, 4715–4719 (2012).

    Article  CAS  Google Scholar 

  24. Chan, T. Y., Partin, A. W., Walsh, P. C. & Epstein, J. I. Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy. Urology 56, 823–827 (2000).

    Article  CAS  Google Scholar 

  25. Issadore, D. et al. Ultrasensitive clinical enumeration of rare cells ex vivo using a micro-hall detector. Sci. Transl. Med. 4, 141ra192 (2012).

    Article  Google Scholar 

Download references


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.

Author information

Authors and Affiliations



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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 4595 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing