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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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.

Author information

Author notes

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

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.

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.

Corresponding author

Correspondence to Sanjiv S. Gambhir.

Supplementary information

  1. Supplementary Information

    Supplementary figures, tables and video captions.

  2. Reporting Summary

  3. Supplementary Video 1

    Trajectories and distribution of magnetic particles along the MagWIRE.

  4. Supplementary Video 2

    Magnetic particle accumulation on MagWIRE.

  5. Supplementary Video 3

    Single-pass method of rapid cell labelling and capture.

  6. Supplementary Video 4

    Fluoroscopy of the highly vascularized porcine ear.

  7. Supplementary Video 5

    Fluoroscopy of the MagWIRE in a porcine ear vein.

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DOI

https://doi.org/10.1038/s41551-018-0257-3