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Quantum nanodiamonds for sensing of biological quantities - Angle, temperature, and thermal conductivity

MetadataDetails
Publication Date2022-01-01
JournalBiophysics and Physicobiology
AuthorsShingo Sotoma, Hirotaka Okita, Shunsuke Chuma, Yoshie Harada
InstitutionsThe University of Osaka, Quantum (Australia)
Citations13
AnalysisFull AI Review Included

Technical Documentation: MPCVD Diamond for Quantum Biosensing

Section titled “Technical Documentation: MPCVD Diamond for Quantum Biosensing”

This review highlights the critical role of Fluorescent Nanodiamonds (FNDs) containing Nitrogen-Vacancy (NV) centers as robust, biocompatible quantum sensors for measuring physical quantities within living cells.

  • Core Application: FNDs enable ultrasensitive nanosensing of intracellular physical parameters, including angle (rotational dynamics), temperature, and thermal conductivity.
  • Quantum Readout: Sensing relies on the distinctive magneto-optical properties of the NV center, read out using Optically Detected Magnetic Resonance (ODMR) or all-optical Zero-Phonon Line (ZPL) shifts.
  • High Precision Achieved: Demonstrated angular uncertainty of 3° (at 1.7 s resolution) for tracking 3D rotational motion of FNDs on cell membranes.
  • Robust Temperature Sensing: NV centers function as robust thermometers, minimally influenced by environmental factors (pH, viscosity), achieving precision down to 0.1 K in living HeLa cells.
  • Novel Thermal Measurement: PDA-coated FNDs were successfully used as hybrid heater/thermometers to measure intracellular thermal conductivity (0.11 ± 0.04 Wm-1 K-1).
  • Material Challenge: Future development requires overcoming material inhomogeneity (size, strain, NV count) and establishing reliable synthesis methods for smaller, high-signal nanodiamonds.
ParameterValueUnitContext
NV Center Zero-Field Splitting (D)2870MHzGround state spin sublevels ms = ±1
NV- ZPL Wavelength637nmFluorescence emission peak
NV0 ZPL Wavelength575nmFluorescence emission peak
Thermal Shift (dD/dT)-75kHz/KODMR temperature sensitivity (280-330 K range)
Angular Uncertainty3°3D rotational tracking resolution (1.7 s time resolution)
Temperature Precision (ODMR)0.1KMeasurement precision achieved in HeLa cells
ZPL Temperature Sensitivity0.015nm/KAll-optical temperature sensing
All-Optical Sensitivity (PHEMA)0.46-1.1K Hz-1/2ZPL shift method (35-120 °C range)
Intracellular Thermal Conductivity0.11 ± 0.04Wm-1 K-1HeLa and MCF-7 cells (95% confidence)
FND Particle Size (General Use)50-100nmStandard biomedical applications

The research relies on advanced material preparation and quantum measurement techniques to achieve intracellular sensing:

  1. NV Center Generation: Fluorescent Nanodiamonds (FNDs) containing negatively charged Nitrogen-Vacancy (NV-) centers are utilized. The quality and concentration of NV centers are critical for signal strength and coherence.
  2. Surface Functionalization: FNDs are coated using non-covalent (e.g., BSA, PEI, Lipids) or covalent (e.g., PDA, Silica, HPG) methods to enhance water solubility, colloidal stability, and enable specific targeting of biomolecules (e.g., EGF receptors).
  3. Optically Detected Magnetic Resonance (ODMR): This technique provides the optical readout of the NV electron spin quantum states. Microwave (MW) irradiation induces electron spin magnetic resonance, resulting in reduced fluorescence emission.
  4. Angular Sensing (Tomographic Vector Magnetometry): An orthogonally aligned three-axis magnet system generates an arbitrary external magnetic field. The Zeeman splitting of the NV spin sublevels is monitored to determine the angle between the magnetic field vector and the NV axis, enabling 3D rotational tracking.
  5. Temperature Sensing (ODMR): Temperature is derived from the shift in the zero-field splitting (D) of the NV ground state, which is highly temperature-dependent (dD/dT = -75 kHz/K).
  6. Thermal Conductivity Measurement: FNDs coated with polydopamine (PDA) are used as a hybrid system (photothermal heater and quantum thermometer). Laser heating is applied, and the resulting temperature rise is measured via ODMR/ZPL shifts to calculate the thermal conductivity of the surrounding cellular environment.

6CCVD provides the high-quality MPCVD diamond materials and precision engineering services necessary to advance quantum biosensing research, specifically addressing the material inhomogeneity and customization challenges noted in the paper.

To replicate or extend this research, particularly focusing on improving material homogeneity and signal quality, 6CCVD recommends:

  • High-Purity Single Crystal Diamond (SCD): SCD wafers (up to 500 ”m thick) serve as ideal precursors for creating highly uniform FNDs via top-down fabrication (e.g., milling or etching). Our SCD offers ultra-low strain (critical for minimizing ODMR signal inhomogeneity) and precise control over nitrogen/boron doping for optimized NV center creation.
  • Boron-Doped Diamond (BDD) Substrates: For researchers developing electrochemical or hybrid sensing platforms, our BDD material provides a conductive, robust, and biocompatible substrate.
  • Optical Grade SCD: For bulk NV ensemble sensing applications that require high-power ODMR systems, 6CCVD supplies large-area, highly polished SCD plates (Ra < 1 nm) with controlled NV density, offering superior crystal quality compared to FND ensembles.

The development of advanced FND sensors requires precise control over geometry and integration with external components (e.g., heaters for thermal conductivity). 6CCVD offers comprehensive customization:

Requirement from Research6CCVD Customization CapabilityTechnical Advantage
Hybrid Sensor Integration (e.g., PDA heater)Custom Metalization: We apply thin films of Au, Pt, Ti, W, or Cu directly onto diamond substrates.Enables the fabrication of integrated heater/sensor platforms or electrical contacts for advanced ODMR setups.
Controlled Geometry (for FND precursors)Custom Dimensions & Thickness: SCD/PCD plates up to 125 mm in diameter and thicknesses from 0.1 ”m to 10 mm.Provides large, uniform source material for high-yield, homogeneous nanodiamond synthesis.
Surface Preparation (for coating/functionalization)Ultra-Precision Polishing: SCD surfaces polished to Ra < 1 nm; PCD surfaces to Ra < 5 nm (inch-size).Ensures optimal surface quality for subsequent chemical functionalization (e.g., HPG, PDA coating) and minimizes surface defects that can degrade NV coherence.
Targeting Specific SitesLaser Cutting & Shaping: Custom laser cutting services for unique geometries or micro-structures.Allows for the creation of specific diamond structures optimized for targeted delivery or integration into microfluidic devices.

6CCVD’s in-house PhD team specializes in the material science of MPCVD diamond and NV center physics. We can assist researchers in:

  • Material Selection: Optimizing the diamond grade (SCD vs. PCD) and doping concentration (Nitrogen/Boron) to maximize NV center yield and coherence time (T2) for specific quantum sensing projects.
  • Strain Management: Providing low-strain SCD substrates essential for high-resolution ODMR measurements, particularly for temperature and magnetic field sensing.
  • Process Integration: Consulting on optimal surface preparation techniques to ensure robust and stable functionalization for biological applications, such as intracellular thermal conductivity measurements.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

Measuring physical quantities in the nanometric region inside single cells is of great importance for understanding cellular activity. Thus, the development of biocompatible, sensitive, and reliable nanobiosensors is essential for progress in biological research. Diamond nanoparticles containing nitrogen-vacancy centers (NVCs), referred to as fluorescent nanodiamonds (FNDs), have recently emerged as the sensors that show great promise for ultrasensitive nanosensing of physical quantities. FNDs emit stable fluorescence without photobleaching. Additionally, their distinctive magneto-optical properties enable an optical readout of the quantum states of the electron spin in NVC under ambient conditions. These properties enable the quantitative sensing of physical parameters (temperature, magnetic field, electric field, pH, etc.) in the vicinity of an FND; hence, FNDs are often described as “quantum sensors”. In this review, recent advancements in biosensing applications of FNDs are summarized. First, the principles of orientation and temperature sensing using FND quantum sensors are explained. Next, we introduce surface coating techniques indispensable for controlling the physicochemical properties of FNDs. The achievements of practical biological sensing using surface-coated FNDs, including orientation, temperature, and thermal conductivity, are then highlighted. Finally, the advantages, challenges, and perspectives of the quantum sensing of FND are discussed. This review article is an extended version of the Japanese article, In Situ Measurement of Intracellular Thermal Conductivity Using Diamond Nanoparticle, published in SEIBUTSU BUTSURI Vol. 62, p. 122-124 (2022).