Nitrogen-vacancy center magnetic imaging of Fe3O4 nanoparticles inside the gastrointestinal tract of Drosophila melanogaster
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2023-12-05 |
| Journal | Nanoscale Advances |
| Authors | Niklas Mathes, Maria Comas, Regina Bleul, Katrijn Everaert, Tobias Hermle |
| Institutions | Physikalisch-Technische Bundesanstalt, Carl Zeiss (Germany) |
| Citations | 8 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive SummaryâThis research demonstrates the feasibility of using Nitrogen-Vacancy (NV) center magnetometry for high-resolution vector magnetic imaging of magnetic nanoparticles (MNPs) within biological tissue.
- Core Achievement: Successful proof-of-principle imaging of Fe3O4 MNP clusters accumulated inside the gastrointestinal (GI) tract of Drosophila melanogaster larvae.
- Resolution Advantage: The widefield NV technique achieved diffraction-limited spatial resolution (sub-1 ”m), offering a significant improvement over conventional preclinical magnetic imaging methods like Magnetic Particle Imaging (MPI) (millimeter resolution).
- Vector Capability: The method allowed for the full reconstruction of the three Cartesian components (Bx, By, Bz) of the MNP stray field, providing detailed information on MNP clustering and magnetization alignment.
- Sensor Specifications: The NV sensor utilized a near-surface layer (~400 nm thick, ~1 ppm NV concentration) in a single-crystal diamond, enabling close proximity (microns standoff) to the biological sample.
- Sensitivity: Calculated shot-noise limited magnetic sensitivity (η) ranged from 5.13 to 7.65 ”T/Hz1/2 across the four NV orientations, confirming sufficient accuracy for MNP detection.
- Qualitative Findings: The MNP distribution clearly followed the outer shape of the dissected organ, and the MNP magnetization was observed to be partially aligned with the external 10 mT bias field.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| MNP Material | Fe3O4 | N/A | Magnetite, single core |
| MNP Core Diameter | ~29 | nm | Determined by TEM |
| NV Sensor Material | Single-crystal diamond | N/A | (100)-surface orientation |
| NV Layer Thickness | ~400 | nm | Estimated from CVD growth |
| NV Concentration | ~1 | ppm | Estimated within the doped layer |
| Spatial Resolution | <1 | ”m | Diffraction-limited (Widefield ODMR) |
| Bias Magnetic Field (Bbias) | ~10 | mT | Applied for Zeeman splitting |
| Measured Bbias (Free Area) | (3.88, 6.08, 4.68) | mT | Cartesian components (x, y, z) |
| Maximum MNP Field Modulation | 1.8 | mT | Observed in the y-component |
| Shot-Noise Limited Sensitivity (η) | 5.13 to 7.65 | ”T/Hz1/2 | Range across four NV orientations |
| ODMR Signal-to-Noise Ratio (SNR) | ~10 | dB | Single pixel measurement |
| Objective Numerical Aperture (NA) | 0.65 | N/A | 20x magnification, long working distance |
| Microwave Frequency Scan Range | 2.725 to 3.025 | GHz | Total range scanned |
| Frequency Step Size | 500 | kHz | ODMR measurement step |
| Sample Standoff (Estimated) | Order of a few | ”m | Distance between MNPs and NV layer |
Key Methodologies
Section titled âKey MethodologiesâThe experiment combined specialized MNP synthesis, biological sample preparation, and advanced widefield NV magnetometry.
- Magnetic Nanoparticle (MNP) Synthesis: Fe3O4 MNPs (~29 nm core) were synthesized via precipitation from alkaline iron chloride solution using a continuous micromixer process, followed by electrostatic stabilization and magnetic purification.
- NV Sensor Fabrication: A dense NV layer (~400 nm thick, ~1 ppm N) was created in a single-crystal diamond via Chemical Vapor Deposition (CVD) overgrowth, followed by electron irradiation and annealing to form the NV centers.
- Biological Loading: Drosophila melanogaster 3rd instar larvae were incubated for 24 hours in phosphate-buffered saline (PBS) containing 100 ”g/mL Fe3O4 MNPs, leading to MNP accumulation in the GI tract.
- Sample Mounting: Larval guts were dissected, fixed in 4% paraformaldehyde, and mounted directly onto the diamond plate, ensuring the tissue was in close proximity (microns) to the NV layer.
- Widefield ODMR Measurement: A home-built widefield NV center magnetometer was used. A 10 mT bias magnetic field was applied to split the NV resonances. The NV centers were excited by a green laser, and the fluorescence was collected by a 20x, NA 0.65 objective and imaged onto an sCMOS camera.
- Frequency Sweeping: Optically Detected Magnetic Resonance (ODMR) spectra were acquired by sweeping the microwave frequency (2.725 GHz to 3.025 GHz) in 500 kHz steps, with 30 repetitions averaged per step to enhance the signal-to-noise ratio.
- Vector Field Reconstruction: The Zeeman splitting maps for the four distinct NV orientations were extracted from the ODMR data. These four projections were then mathematically transformed using the known diamond lattice orientation to reconstruct the full three-dimensional (x, y, z) magnetic field vector generated by the MNPs.
Commercial Applications
Section titled âCommercial ApplicationsâThe high-resolution, non-destructive vector magnetic imaging capability of NV centers is highly relevant across several advanced technology sectors.
- Biomedical Research and Diagnostics:
- Targeted Drug Delivery: Visualizing the precise location, density, and clustering of functionalized MNPs used as drug carriers within cells or thin tissue sections.
- Preclinical Imaging: Providing ultra-high-resolution âzoom-inâ capability to complement lower-resolution techniques (like MPI or MRI) for detailed analysis of MNP pharmacokinetics.
- Physiological Process Tracking: Monitoring the distribution of MNPs used to track specific physiological processes or organ-organ communication (e.g., in intestinal models).
- Quantum Sensing and Metrology:
- Compact Magnetometers: Development of miniaturized, portable, and integrated NV sensors for magnetic field mapping in complex environments.
- Material Characterization: High-resolution mapping of magnetic domains and stray fields in thin films and novel magnetic materials.
- Therapeutic Optimization:
- Magnetic Hyperthermia: Quantifying MNP density distributions in situ to optimize the efficiency and targeting accuracy of cancer treatment protocols based on selective heating.
- Advanced MRI:
- High Spatial Resolution MRI: Utilizing NV layers to detect alternating magnetic fields generated by MNPs, potentially enabling high-resolution MRI signal detection beyond current limitations.
View Original Abstract
Widefield magnetometry based on nitrogen-vacancy centers enables high spatial resolution imaging of magnetic field distributions without a need for spatial scanning.