Quantum measurement and orientation tracking of fluorescent nanodiamonds inside living cells

Journal name:
Nature Nanotechnology
Volume:
6,
Pages:
358–363
Year published:
DOI:
doi:10.1038/nnano.2011.64
Received
Accepted
Published online

Abstract

Fluorescent particles are routinely used to probe biological processes1. The quantum properties of single spins within fluorescent particles have been explored in the field of nanoscale magnetometry2, 3, 4, 5, 6, 7, 8, but not yet in biological environments. Here, we demonstrate optically detected magnetic resonance of individual fluorescent nanodiamond nitrogen-vacancy centres inside living human HeLa cells, and measure their location, orientation, spin levels and spin coherence times with nanoscale precision. Quantum coherence was measured through Rabi and spin-echo sequences over long (>10 h) periods, and orientation was tracked with effective 1° angular precision over acquisition times of 89 ms. The quantum spin levels served as fingerprints, allowing individual centres with identical fluorescence to be identified and tracked simultaneously. Furthermore, monitoring decoherence rates in response to changes in the local environment may provide new information about intracellular processes. The experiments reported here demonstrate the viability of controlled single spin probes for nanomagnetometry in biological systems, opening up a host of new possibilities for quantum-based imaging in the life sciences.

At a glance

Figures

  1. Quantum measurement of single spins in living cells.
    Figure 1: Quantum measurement of single spins in living cells.

    a, Experimental setup, including microwave (MW) control of the NV spin levels and confocal fluorescence readout. b, Overlay of bright-field and confocal fluorescence images of HeLa cells, showing uptake of nanodiamonds. NV fluorescence is shown in red and the nucleus is stained with Hoechst 33342 (blue). Images were obtained on a Leica TCS SP2 confocal microscope. c, Atomic lattice structure of the NV centre. d, Quantum measurement and control of the NV centre. Left: energy levels of the NV probe system and fluorescence dynamics. Middle: quantum control for Studies 1 and 2 (π and π/2 pulses for spin-echo). Right: orientation-dependent Zeeman splitting Δω(θ) in an applied magnetic field B0, measured in Study 3.

  2. Confocal image of a HeLa cell containing two isolated nanodiamonds with single NV centres and their measured ODMR spectra.
    Figure 2: Confocal image of a HeLa cell containing two isolated nanodiamonds with single NV centres and their measured ODMR spectra.

    ac, Confocal image of HeLa-1 (c, z = 11 µm above the cover glass; edge of the microwave antenna cladding is visible at the top of the image), with fluorescence gated around the NV emission (650–800 nm). The nucleus and cell membrane are indicated with dashed lines for clarity. The optically detected magnetic resonance (ODMR) spectra of NV-1a (a) and NV-1b (b) show the different strain splitting between the two centres.

  3. Quantum coherence properties of the probes NV-1a and NV-1b in HeLa-1.
    Figure 3: Quantum coherence properties of the probes NV-1a and NV-1b in HeLa-1.

    a,b, Rabi oscillations of NV-1a and NV-1b measured at various times during the lifetime of the cell. c, Initial spin-echo measurements on both NV centres (statistical errors are at the 1% level). d, Time evolution of the decoherence rates extracted from the spin-echo profiles for both NV centres. The uncertainties in the extracted values, quoted at the one sigma level, are determined from the fit to the data.

  4. NV axis rotation owing to motion of the nanodiamonds in HeLa-1.
    Figure 4: NV axis rotation owing to motion of the nanodiamonds in HeLa-1.

    a, With constant MW power, the Rabi frequency is governed by orientation φ of the NV axis with respect to the MW driving field. b, Upper bounds on the change in orientation of the nanodiamonds based on a maximum initial perpendicular alignment of the higher Rabi frequency centre (NV-1b) with the MW field (see Supplementary Information). c, Confocal scan sequence showing the corresponding morphological changes in the cell during the same timeframe.

  5. Orientation tracking of NV-2 in HeLa-2.
    Figure 5: Orientation tracking of NV-2 in HeLa-2.

    a, Changes in the orientation of the NV quantization axis relative to the external magnetic field owing to nanodiamond motion are manifest in the orientation-dependent Zeeman splitting Δω(θ) observed in the ODMR spectrum shown at various times over the HeLa-2 cell lifetime. b, Measured orientation of the nanodiamond as a function of time, and comparison of different acquisition rates. c, Four-dimensional tracking (position and orientation) of NV-2 in HeLa-2 over a 3 h period.

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Author information

Affiliations

  1. School of Physics, University of Melbourne, Victoria 3010, Australia

    • L. P. McGuinness,
    • A. Stacey,
    • D. A. Simpson,
    • L. T. Hall,
    • D. Maclaurin,
    • S. Prawer,
    • R. E. Scholten &
    • L. C. L. Hollenberg
  2. Centre for Quantum Computation and Communication Technology, School of Physics, University of Melbourne, Victoria 3010, Australia

    • L. P. McGuinness,
    • D. A. Simpson,
    • L. T. Hall,
    • D. Maclaurin &
    • L. C. L. Hollenberg
  3. Centre for Nanoscience and Nanotechnology, Department of Chemical and Biomolecular Engineering, University of Melbourne, Victoria 3010, Australia

    • Y. Yan &
    • F. Caruso
  4. School of Chemistry and Bio21 Institute, University of Melbourne, Victoria 3010, Australia

    • P. Mulvaney
  5. 3. Physikalisches Institut, Universität Stuttgart, Pfaffenwaldring, D-70550 Stuttgart, Germany

    • J. Wrachtrup
  6. Centre for Coherent X-ray Science, School of Physics, University of Melbourne, Victoria 3010, Australia

    • R. E. Scholten

Contributions

L.P.M., A.S., D.S. and R.E.S. designed and constructed the confocal/ESR system, performed the measurements and carried out the data analysis. Y.Y. and F.C. planned and conducted the cellular uptake experiments, and analysed the data. D.M., L.T.H. and L.C.L.H. carried out the theoretical analyses. L.C.L.H., J.W., F.C., P.M. and S.P. conceived and directed the project. L.C.L.H. wrote the paper with contributions from all authors.

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The authors declare no competing financial interests.

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