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An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo

Nature Biomedical Engineering volume 2, pages 696–705 (2018)Cite this article

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Abstract

The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5–10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject’s blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labelled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labelling and single-pass capture of viable model CTCs in less than 10 s. The wire achieves capture efficiencies that correspond to enrichments of 10–80 times the amount of CTCs in a 5-ml blood draw, and 500–5,000 times the enrichments achieved using the commercially available Gilupi CellCollector.

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Fig. 1: Schematic of the MagWIRE concept.
Fig. 2: Numerical simulations of the magnetic properties of a MagWIRE segment.
Fig. 3: CTC capture from buffer and blood in a continuous flow closed-loop system.
Fig. 4: CTC capture in single-pass flow in vitro and in vivo.
Fig. 5: Capture efficiencies for two uses of the MagWIRE: continuous versus single-pass flow.

Change history

  • 18 December 2019

    In the version of this Article originally published, the ORCID for Sanjiv S. Gambhir was incorrect; the correct ORCID is 0000-0002-2711-7554. This has now been amended.

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Acknowledgements

We thank D. Sze, A. Thakor, M. Mahmoudi, H. Nejadnik, T. Larson, A. de Souza and H. Tom Soh for discussions. We also thank Pork Power Farms for their help in choosing suitable pigs for the study. We would also like to acknowledge the Veterinary Service Center and Animal Diagnostic Laboratory at Stanford. This research was supported by the US National Institutes of Health (NIH) Awards U54CA151459 (Center for Cancer Nanotechnology Excellence and Translation) and R21CA185804 (to S.S.G. and S.X.W.), the Canary Foundation (to S.S.G.), and the Ben and Catherine Ivy Foundation. The authors also acknowledge funding support from the NIH Shared Instrument Grant S10 RR026714.

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Author notes

  1. These authors contributed equally: Ophir Vermesh, Amin Aalipour, T. Jessie Ge.

Authors and Affiliations

  1. Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA

    Ophir Vermesh, Amin Aalipour, T. Jessie Ge, Israt S. Alam, Seung-min Park, Hamed Arami & Sanjiv S. Gambhir

  2. Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA

    Ophir Vermesh, Amin Aalipour, T. Jessie Ge, Yamil Saenz, Israt S. Alam, Seung-min Park, Michael H. Bachmann, Kerstin Mueller, Hamed Arami & Sanjiv S. Gambhir

  3. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Amin Aalipour

  4. Howard Hughes Medical Institute, Chevy Chase, MD, USA

    T. Jessie Ge

  5. Department of Electrical Engineering, Stanford University, Stanford, CA, USA

    Yue Guo & Shan X. Wang

  6. Department of Chemistry, Stanford University, Stanford, CA, USA

    Charlie N. Adelson, Jennifer K. Lyons & Edward I. Solomon

  7. Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

    Yoshiaki Mitsutake & Alfredo Green

  8. Department of Comparative Medicine, Stanford University, Stanford, CA, USA

    Jose Vilches-Moure & Elias Godoy

  9. Department of Pediatrics, Stanford University, Stanford, CA, USA

    Michael H. Bachmann

  10. Department of Chemical Engineering, Stanford University, Stanford, CA, USA

    Chin Chun Ooi

  11. Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA

    Shan X. Wang

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Contributions

O.V., A.A., T.J.G. and S.S.G conceived and designed the research. O.V., A.A. and T.J.G. performed all experiments. O.V., A.A., T.J.G., S.-m.P., C.N.A., E.I.S., S.X.W. and S.S.G analysed the data. T.J.G. and Y.G. performed the computational modelling. Y.M., Y.S., J.K.L, A.G. and K.M. aided with the porcine model. O.V., I.S.A., C.N.A., J.V.-M., E.G. and E.I.S. conducted and analysed the toxicity, biodistribution and pharmacokinetic studies. C.C.O. and H.A. aided with MP characterization. M.H.B. contributed cell culture expertise and reagents. O.V., A.A., T.J.G., S.-m.P. and S.S.G drafted the manuscript with input from all of the authors.

Corresponding author

Correspondence to Sanjiv S. Gambhir.

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Competing interests

O.V., A.A., T.J.G., S.-m.P, and S.S.G. have filed for patent protection for the MagWIRE technology. The remaining authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary figures, tables and video captions.

Reporting Summary

Supplementary Video 1

Trajectories and distribution of magnetic particles along the MagWIRE.

Supplementary Video 2

Magnetic particle accumulation on MagWIRE.

Supplementary Video 3

Single-pass method of rapid cell labelling and capture.

Supplementary Video 4

Fluoroscopy of the highly vascularized porcine ear.

Supplementary Video 5

Fluoroscopy of the MagWIRE in a porcine ear vein.

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Vermesh, O., Aalipour, A., Ge, T.J. et al. An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo. Nat Biomed Eng 2, 696–705 (2018). https://doi.org/10.1038/s41551-018-0257-3

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