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Single-cell magnetic imaging using a quantum diamond microscope

Nature Methods volume 12, pages 736–738 (2015)Cite this article

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Abstract

We apply a quantum diamond microscope for detection and imaging of immunomagnetically labeled cells. This instrument uses nitrogen-vacancy (NV) centers in diamond for correlated magnetic and fluorescence imaging. Our device provides single-cell resolution and a field of view (∼1 mm2) two orders of magnitude larger than that of previous NV imaging technologies, enabling practical applications. To illustrate, we quantified cancer biomarkers expressed by rare tumor cells in a large population of healthy cells.

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Figure 1: Quantum diamond microscope for magnetically labeled targets.
Figure 2: Wide-field imaging for quantitative magnetic measurement of biomarker expression on multiple cell lines.

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Acknowledgements

The authors thank M.L. McKee for help with electron microscopy, as well as M. Liong and H. Shao for advice on magnetic assay protocols. This work was supported in part by US National Institutes of Health grants R01HL113156 (H.L.) and U54-CA119349 (R.W.) as well as the US Defense Advanced Research Projects Agency (DARPA) QuASAR program and DARPA SBIR contract W31P4Q-13-C-0064.

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Author notes

  1. David R Glenn and Kyungheon Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Harvard-Smithsonian Center for Astrophysics, Cambridge, Massachusetts, USA

    David R Glenn & Ronald L Walsworth

  2. Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA

    Kyungheon Lee, Ralph Weissleder & Hakho Lee

  3. Department of Physics, Harvard University, Cambridge, Massachusetts, USA

    Hongkun Park, Amir Yacoby, Mikhail D Lukin & Ronald L Walsworth

  4. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA

    Hongkun Park

  5. Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA

    Hongkun Park & Ronald L Walsworth

  6. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA

    Ralph Weissleder

  7. Quantum Diamond Technologies, Inc., Somerville, Massachusetts, USA

    Colin B Connolly

Authors
  1. David R Glenn
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  2. Kyungheon Lee
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  8. Ronald L Walsworth
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Contributions

D.R.G. and R.L.W. designed and constructed the quantum diamond microscope. C.B.C., H.L. and R.L.W. conceived the application of the quantum diamond microscope to the task of rare-cell detection and devised the experiments. K.L., R.W. and H.L. developed the optimal protocol for magnetic labeling of cells. K.L. prepared magnetic nanoagents and carried out the cell labeling. D.R.G. and C.B.C. performed the experiments and analyzed the data. C.B.C., D.R.G., K.L., H.L. and R.L.W. wrote the manuscript, with discussion and input from all authors. A.Y., H.P., M.D.L. and R.L.W. conceived the application of NV diamond wide-field magnetic imaging to biomagnetism.

Corresponding authors

Correspondence to Hakho Lee, Ronald L Walsworth or Colin B Connolly.

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Competing interests

M.D.L. and R.L.W. are cofounders of Quantum Diamond Technologies, Inc. (QDTI). M.D.L., R.L.W. and A.Y. all serve on the Scientific Advisory Board of QDTI and have financial interests in QDTI. R.W. has financial interest in T2Biosystems. R.W.'s interests are reviewed and managed by MGH and Partners HealthCare in accordance with their conflict of interest policies.

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Glenn, D., Lee, K., Park, H. et al. Single-cell magnetic imaging using a quantum diamond microscope. Nat Methods 12, 736–738 (2015). https://doi.org/10.1038/nmeth.3449

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