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Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets

Nature Nanotechnology volume 8, pages 735–741 (2013)Cite this article

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An Erratum to this article was published on 07 November 2013

This article has been updated

Abstract

The spread of cancer throughout the body is driven by circulating tumour cells (CTCs)1. These cells detach from the primary tumour and move from the bloodstream to a new site of subsequent tumour growth. They also carry information about the primary tumour and have the potential to be valuable biomarkers for disease diagnosis and progression, and for the molecular characterization of certain biological properties of the tumour. However, the limited sensitivity and specificity of current methods for measuring and studying these cells in patient blood samples prevents the realization of their full clinical potential. The use of microfluidic devices is a promising method for isolating CTCs2,3. However, the devices are reliant on three-dimensional structures, which limits further characterization and expansion of cells on the chip. Here we demonstrate an effective approach to isolating CTCs from blood samples of pancreatic, breast and lung cancer patients, by using functionalized graphene oxide nanosheets on a patterned gold surface. CTCs were captured with high sensitivity at a low concentration of target cells (73 ± 32.4% at 3–5 cells per ml blood).

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Figure 1: Graphene oxide chip and functionalization/characterization of graphene oxide.
Figure 2: Characterization of the graphene oxide chip with cells in buffer solution.
Figure 3: Characterization of the graphene oxide chip with MCF-7 cells spiked into whole blood.
Figure 4: Fluorescence microscope images and quantification of CTCs captured from cancer patient samples.

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  • 01 October 2013

    In the version of this Letter originally published, in Fig. 1b one of the PEG chains was misplaced. This has now been corrected in the HTML and PDF versions.

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Acknowledgements

The authors thank K. Herman and S. Laurinec for procurement of patient blood samples, and S. Fouladdel for technical help with qRT-PCR. This work was supported by the National Institutes of Health (NIH) Director's New Innovator Award (1DP2OD006672-01), a Career Development Program of the Gastrointestinal Specialized Program of Research Excellence (GI SPORE) award (CA130810), and a 3M non-tenured Faculty Award. The work was performed in part at the Lurie Nanofabrication Facility, a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Hyeun Joong Yoon, Tae Hyun Kim, Zhuo Zhang, Trinh M. Pham & Sunitha Nagrath

  2. Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Tae Hyun Kim

  3. Department of Internal Medicine, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Ebrahim Azizi, Costanza Paoletti, Nithya Ramnath, Max S. Wicha & Daniel F. Hayes

  4. Department of Surgery, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Jules Lin & Diane M. Simeone

  5. Translational Oncology Program, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Max S. Wicha, Diane M. Simeone & Sunitha Nagrath

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  1. Hyeun Joong Yoon
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Contributions

H.Y. and S.N. conceived and designed the study. H.Y. and T.K. fabricated devices and performed the experiments. T.K., Z.Z. and T.P. performed the cell culture. E.A. analysed the RNA data. C.P., J.L., N.R., M.W., D.H. and D.S. prepared the clinical samples. H.Y. and S.N. analysed the data and co-wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Sunitha Nagrath.

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The authors declare no competing financial interests.

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Yoon, H., Kim, T., Zhang, Z. et al. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nature Nanotech 8, 735–741 (2013). https://doi.org/10.1038/nnano.2013.194

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