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A biocompatible technique for magnetic field sensing at (sub)cellular scale using Nitrogen-Vacancy centers

MetadataDetails
Publication Date2020-10-21
JournalEPJ Quantum Technology
AuthorsEttore Bernardi, Ekaterina Moreva, Paolo Traina, Giulia Petrini, Sviatoslav Ditalia Tchernij
InstitutionsAustralian Nuclear Science and Technology Organisation, University of Turin
Citations9
AnalysisFull AI Review Included
  • Core Achievement: Demonstrated a biocompatible Nitrogen-Vacancy (NV) center magnetometry technique achieving a high sensitivity of 68 ± 3 nT/√Hz at a highly localized (sub)cellular sensing volume.
  • Sensing Scale: The sensing volume is defined by a 15 nm thick NV layer and a 10 x 10 ”m2 laser spot, resulting in a volume of 0.015 x 10 x 10 ”m3, significantly smaller than volumes used in previous macroscopic biological experiments.
  • Methodology: Utilizes a lock-in based Optically Detected Magnetic Resonance (ODMR) protocol, enhanced by simultaneous microwave excitation of the three 14N hyperfine resonances.
  • Sensitivity Enhancement: Simultaneous three-tone excitation increased the figure of merit (slope b) of the Lock-in Amplifier (LIA) signal by a factor of approximately 1.5 compared to single-tone excitation.
  • Biocompatibility: The method addresses the sensitivity/power trade-off; while maximum sensitivity was achieved at 80 mW, a conservative biocompatible power of greater than 10 mW is estimated, yielding a sustainable sensitivity of less than 200 nT/√Hz.
  • Future Impact: This setup is suitable for in-vitro measurement of biological magnetic fields at the subcellular scale, enabling the experimental study of processes like action potential generation inside cultivated cells.
ParameterValueUnitContext
Magnetic Sensitivity (Max)68 ± 3nT/√HzAchieved at 80 mW optical power.
Biocompatible Sensitivity (Est.)less than 200nT/√HzEstimated conservative limit at 10 mW optical power.
Sensing Volume (Total)0.015 x 10 x 10”m3NV layer thickness x Laser spot area.
NV Layer Thickness (z-axis)~15nmFormed by implantation and annealing.
NV Layer Depth~10nmDistance from the sample surface.
Laser Spot Size (x-y plane)~10 x 10”m2Focused excitation beam diameter.
Excitation Wavelength532nmSecond harmonic of Nd:YAG laser.
Maximum Optical Power Used80mWUsed for maximum sensitivity measurement.
Estimated Biocompatible Powergreater than 10mWConservative estimate for living cells.
NV Concentration~3 x 1019cm-3Concentration within the 15 nm layer.
ODMR Spin Resonance Frequency2.87GHzCenter frequency of the resonance.
Hyperfine Splitting (Aorth)2.16MHzSeparation used for simultaneous three-tone excitation.
ODMR Linewidth (ΔΜ)1.072MHzMeasured from the central dip.
LIA Time Constant (LSD Noise)300”sUsed for Linear Spectral Density (LSD) measurement.
LIA Time Constant (Spectrum)1msUsed for LIA spectrum construction.
  1. Diamond Substrate Preparation:

    • Started with a 3 x 3 x 0.3 mm3 “optical grade” CVD diamond substrate (ElementSix).
    • Nominal concentration of substitutional nitrogen and boron was less than 1 ppm and 0.05 ppm, respectively.
  2. NV Center Formation (Implantation and Annealing):

    • Implanted with 10 keV N ions at room temperature using a low energy ion implanter.
    • Implantation fluence (dose) was 1 x 1014 cm-2.
    • The sample was subsequently annealed for 2 hours at a temperature of 950 °C.
    • This process created a NV-rich layer of ~15 nm thickness, localized ~10 nm from the surface.
  3. Optical Excitation and Control:

    • Excitation light (532 nm) was generated by the second harmonic of a Nd:YAG laser (Coherent Prometheus 100NE).
    • An Acousto Optic Modulator (AOM) was used to switch the laser illumination on/off, reducing total light energy delivered to the sample.
    • The beam was focused through an air objective (NA = 0.67) to a spot size of ~10 x 10 ”m2.
  4. Microwave (MW) Control and ODMR:

    • MW control was provided by a commercial generator (Keysight N5172B) connected to a planar ring antenna.
    • The MW signal was internally frequency modulated at fmod = 5001 Hz with a modulation depth fdev = 0.5 MHz.
    • Simultaneous Hyperfine Driving: The MW signal was mixed with a ~2.16 MHz sinewave via a double-balanced mixer to generate three simultaneous driving frequencies, addressing all three 14N hyperfine resonances for enhanced sensitivity.
  5. Detection and Lock-in Amplification (LIA):

    • Photoluminescence (PL) was spectrally filtered (532 nm notch, 650 nm long-pass).
    • 96% of the PL intensity was collected onto a photodetector (Thorlabs DET 10A2) and sent to the LIA input channel.
    • The LIA read the resulting modulated photoluminescence signal, which is linearly proportional to the ODMR shift (and thus the magnetic field variation).
  • High-Resolution Biomagnetometry:

    • Intracellular Sensing: Direct measurement of magnetic fields generated by ion currents (e.g., K+, Na+) within single neurons or cardiac cells, overcoming the limitations of SQUID magnetometers.
    • Neurodegenerative Research: High-resolution mapping of neuronal action potentials for timely detection and study of psychic and neurodegenerative disorders.
  • Quantum Sensor Development:

    • Integrated Diamond Chips: Fabrication of diamond substrates with shallow NV layers optimized for surface sensing and integration into microfluidic or biological platforms.
    • Pulsed Sensing Systems: Implementation of advanced pulsed ODMR techniques (e.g., Ramsey sequences) to further increase contrast and extend the coherence time (T2) for superior sensitivity.
  • Non-Invasive Diagnostics:

    • Cardiac Mapping: Developing a new generation of non-invasive diagnostic and therapeutic techniques based on measuring magnetic fields produced by heart currents.
  • Material Science and Thin Film Analysis:

    • The core technology (shallow NV layer, high sensitivity) is applicable to high-resolution magnetic imaging of thin films and surfaces in materials research, especially where localized field mapping is critical.
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