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6CCVD Research

Multimodal quantum metrology in living systems using nitrogen-vacancy centres in diamond nanocrystals

At a Glance

Section titled “At a Glance”
MetadataDetails
Publication Date2023-08-01
JournalFrontiers in Quantum Science and Technology
AuthorsJack W. Hart, Helena S. Knowles
InstitutionsUniversity of Cambridge
Citations4
AnalysisFull AI Review Included

Executive Summary

Section titled “Executive Summary”

This analysis focuses on the engineering and application of Nitrogen-Vacancy (NV) centers embedded in nanodiamonds (NDs) for multimodal quantum metrology within living biological systems.

  • Core Value Proposition: NV-NDs provide robust, nanoscale quantum sensors capable of operating under ambient conditions (room temperature) with exceptional electronic spin coherence and optical addressability.
  • Multimodal Capability: The platform integrates multiple sensing modalities—including thermometry, magnetometry, electric field sensing, and local spin detection (NMR/T1 relaxometry)—into a single nanoparticle device.
  • Nanoscale Resolution: Sensing is achieved in ultra-small volumes, demonstrated down to 7 zeptolitres (zL), enabling the detection of phenomena like local temperature gradients and molecular structure (NMR) at the sub-cellular level.
  • Biosensing Advantages: NDs exhibit low cytotoxicity, superior photostability compared to conventional fluorescent dyes (half-life >> 100s of seconds), and straightforward cellular uptake, facilitating long-term in vivo tracking.
  • Engineering Challenges & Solutions: The dynamic nature of living systems causes ND translation (up to 200 nm/s) and rotation (up to 5 °/s). These issues are mitigated using reactive tracking techniques and active localization via infrared optical trapping.
  • Future Direction: Focus is on developing interleaved protocols for simultaneous parameter measurement and optimizing pulsed excitation schemes (optical and microwave) to minimize localized thermal load and cytotoxicity.

Technical Specifications

Section titled “Technical Specifications”
ParameterValueUnitContext
Sensor MaterialNitrogen-Vacancy (NV) CentersN/AEmbedded in diamond nanocrystals (NDs).
Typical Probing Volume10s of zeptolitreszLCorresponds to volume of a 50 nm diameter sphere.
NMR Sensing Volume (Single NV)7 zeptolitreszLDemonstrated detection of ~1500 oil molecules.
Conventional NMR Sample Volume~1mm3Required for standard NMR spectroscopy.
Conventional NMR Magnetic FieldSeveralTeslaRequired for standard NMR spectroscopy.
NV Excitation WavelengthCommonly 532nmUsed for continuous spin initialization and readout.
T1 Relaxation Time ScaleMicrosecondsUsed for relaxometry sensing modality.
Maximum Intracellular Translation SpeedUp to 200nm/sActive transport by motor proteins.
Maximum Nanodiamond Rotation Speed5°/sDemonstrated tracking speed on cell membranes.
Fluorescent Dye Photobleaching Half-Life~100ssecondsNV centers offer superior photostability.
Observed Mitochondrial Temperature (Debated)Close to 50°CObserved local gradients in mitochondrial intermembrane space.

Key Methodologies

Section titled “Key Methodologies”

The following methodologies are critical for realizing multimodal quantum metrology using NV-NDs in living systems:

  1. Optically Detected Magnetic Resonance (ODMR): The standard readout technique. It involves monitoring the NV center’s photoluminescence (PL) signal while applying external microwave (MW) radiation. A shift in the ground state spin energy levels (ms = 0 to ms = ±1) indicates changes in local temperature, magnetic field, or strain.
  2. T1 Relaxometry: A spin-based modality that does not require coherent MW control. The spin relaxation time (T1) is measured by monitoring the change in PL between spin initialization and a finite relaxation time (typically microsecond scale). T1 is sensitive to local electromagnetic noise, providing an indication of temperature or free radical concentration (e.g., Reactive Oxygen Species).
  3. Passive Microrheology: Analyzing the motion of the ND probe within the cell by calculating the Mean Squared Displacement (MSD). The power-law exponent (α) of the MSD determines the local rheological properties (α < 1 indicates sub-diffusive/viscoelastic medium; α > 1 indicates super-diffusive/active transport).
  4. Charge State Conversion (Voltage Sensing): Exploiting the transition between the negatively charged (NV-) and neutral (NV0) states. A strong local electrostatic field can shift the NV energy levels relative to the diamond Fermi energy, facilitating voltage-dependent charge state conversion, detectable via PL changes.
  5. Motion Compensation and Tracking: Due to active intracellular transport, ND movement (translation and rotation) must be managed. Reactive tracking techniques compensate for translational movement. Rotational diffusion rates are inferred from the change in the ODMR resonance angle relative to a fixed external magnetic field.
  6. Active Localization via Optical Trapping: High refractive index contrast allows NDs to be physically held or moved using infrared optical traps. This enables targeted sensing in specific organelles and facilitates active microrheology by probing the environment’s response to a driven force.
  7. Thermal Load Mitigation: To prevent damage from continuous excitation (532 nm laser and MW radiation), strategies include designing waveguide structures for targeted, lower-power MW delivery, and using pulsed illumination/MW sequences to allow time for heat conduction away from the sample.

Commercial Applications

Section titled “Commercial Applications”

The unique capabilities of NV-ND quantum sensors are poised to impact several high-tech and biomedical sectors:

  • Biomedical Diagnostics: Developing ultrasensitive diagnostics for biomarker detection, offering orders of magnitude enhanced sensitivity compared to current clinical methods.
  • Cellular and Molecular Biology Research: Providing quantitative, high-resolution tools for understanding fundamental cellular processes, such as heat transfer (addressing the debate on intracellular temperature gradients), mitochondrial function (thermogenic effects), and cytoskeletal dynamics (microrheology).
  • Drug Development and Delivery: Enabling nanoparticle-based drug delivery systems where the NV sensor is integrated to monitor local physiological conditions (e.g., pH, temperature, viscosity) or track drug release in vivo.
  • Neuroscience: High-sensitivity magnetic field sensing (magnetometry) for detecting transient, small magnetic signals, such as action potentials in single neurons, or imaging magnetosomes generated by bacteria.
  • Advanced Materials Characterization: Utilizing nanoscale NMR spectroscopy to resolve chemical shifts and structural information of molecules and proteins in extremely small, localized volumes (zeptolitres), relevant for characterizing novel materials or complex biological samples.
  • Quantum Technology Development: Serving as a testbed for robust quantum control techniques (e.g., SEDOR, optimal control) in complex, dynamic environments, informing the design of next-generation solid-state quantum sensors and quantum memory elements.
View Original Abstract

Nitrogen-vacancy centres in diamond nanocrystals are among the leading candidates for realising nanoscale quantum sensing under ambient conditions. Due to their exceptional electronic spin coherence at room temperature and optical addressability, these solid state spin-based sensors can achieve a wide selection of sensing modalities, including probing temperature, external magnetic and electric field, as well as the detection of nearby electronic and nuclear spins. In this article, we discuss recent progress made utilizing nanodiamond quantum sensors in living systems and explore both opportunities for future advances and challenges that lie ahead.

Tech Support

Section titled “Tech Support”

Original Source

Section titled “Original Source”

References

Section titled “References”
  1. 2010 - Temperature dependence of the nitrogen-vacancy magnetic resonance in diamond [Crossref]
  2. 2017 - Nanoscale nuclear magnetic resonance with chemical resolution [Crossref]
  3. 2014 - A critique of methods for temperature imaging in single cells [Crossref]
  4. 2020 - Sensitivity optimization for nv-diamond magnetometry [Crossref]
  5. 2016 - Optical magnetic detection of single-neuron action potentials using quantum defects in diamond [Crossref]
  6. 2020 - Silicon carbide color centers for quantum applications [Crossref]
  7. 2020 - Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents [Crossref]
  8. 2020 - Optical thermometry with quantum emitters in hexagonal boron nitride [Crossref]
  9. 2020 - Probing and manipulating embryogenesis via nanoscale thermometry and temperature control [Crossref]
  10. 2018 - Mitochondria are physiologically maintained at close to 50 c [Crossref]

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