Hyperpolarization-Enhanced NMR Spectroscopy with Femtomole Sensitivity Using Quantum Defects in Diamond
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2020-06-09 |
| Journal | Physical Review X |
| Authors | Dominik Bucher, David R. Glenn, Hongkun Park, Mikhail D. Lukin, Ronald L. Walsworth |
| Institutions | Center for Astrophysics Harvard & Smithsonian, Technical University of Munich |
| Citations | 83 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive Summaryâ- Core Achievement: Successful integration of Overhauser Dynamic Nuclear Polarization (DNP) with picoliter-scale Nitrogen-Vacancy (NV) ensemble NMR spectroscopy (DNP-NV-NMR).
- Sensitivity Breakthrough: Achieved femtomole (50 fmol) molecule-number sensitivity, representing a greater than two orders of magnitude improvement over previous NV-NMR methods.
- Performance Metrics: Demonstrated a proton number sensitivity of ~10 pmol/(Hz)1/2, enabling high-resolution spectroscopy on dilute solutions.
- Enhancement Factor: Observed a ~230x signal enhancement in water samples due to DNP using TEMPOL molecular radicals at a low bias field (84.7 mT).
- High Resolution: Maintained high spectral resolution (~8-10 Hz linewidths) sufficient to observe chemical shifts and J-couplings in various small organic molecules (e.g., xylene, thymine).
- Technical Implementation: The system uses a 12C-enriched CVD diamond chip with a 13 ”m 14N-doped surface layer, defining a small sensing volume (~10 pL). The existing GHz-frequency antenna is leveraged for both NV spin manipulation and DNP driving.
- Impact: The technique advances mass-limited NMR spectroscopy, opening pathways for applications in single-cell analysis, metabolomics, and high-throughput drug screening.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Molecule Number Sensitivity (LOD) | 50 | femtomole | Limit of detection (SNR=3) for t-BuOD |
| Proton Number Sensitivity | 10 | pmol/(Hz)1/2 | Hyperpolarized water sample (SNR=3) |
| DNP Signal Enhancement | ~230 | x | Compared to non-DNP control |
| Effective NMR Sensing Volume | ~10 | pL | Defined by laser spot size on diamond |
| Bias Magnetic Field (B0) | 84.7 | mT | Operating field for NV-NMR |
| NV Resonance Frequency | ~500 | MHz | Electron spin transition frequency |
| TEMPOL ESR Frequency | ~2.37 | GHz | Overhauser drive frequency |
| Proton NMR Frequency | ~3.606 | MHz | FNP detection frequency |
| NV Ensemble Density | ~3x1017 | cm-3 | In the 13 ”m surface layer |
| Surface Layer Thickness | 13 | ”m | 14N-enriched layer on diamond |
| Diamond T2* (Ramsey) | ~750 | ns | NV ensemble coherence time |
| Diamond T2 (Hahn Echo) | ~6.5 | ”s | NV ensemble coherence time |
| Proton Spin Lifetime (T1) | ~150 | ms | With 20 mM TEMPOL radical |
| Laser Wavelength (λ) | 532 | nm | Green laser for NV readout |
| Laser Spot Diameter | ~20 | ”m | Defining active sensor area |
| Magnetometer Noise Floor | ~20 | pT/Hz-1/2 | NV ensemble sensor performance |
| Spectral Linewidth (Îf) | 8-10 | Hz | Observed in molecular spectra |
| Maximum DNP Rabi Frequency | ~10 | MHz | Optimized drive power for DNP |
Key Methodologies
Section titled âKey MethodologiesâThe DNP-enhanced NV-NMR system relies on combining specialized diamond fabrication, precise microwave control, and a synchronized readout sequence.
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Diamond Sensor Preparation:
- Substrate: 12C enriched (99.999%) Chemical Vapor Deposition (CVD) diamond chip (2mm x 2mm x 0.5 mm).
- NV Layer Growth: A 13 ”m thick surface layer was grown with high 14N density (~4.8 x 1018 cm-3).
- NV Creation: Electron irradiation (flux 1.3 x 1014 cm-2 s-1) followed by annealing at 800 °C yielded a dense NV ensemble (~3x1017 cm-3).
- Optical Geometry: Diamond edges were polished at 45° to enable laser excitation via total internal reflection (TIR), minimizing light exposure to the liquid sample.
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Magnetic and Microwave Setup:
- Bias Field (B0): A feedback-stabilized electromagnet provided B0 = 84.7 mT, aligned parallel to the diamondâs [111] axis.
- Antenna: A 1 mm diameter wire loop antenna, mounted immediately above the diamond, was used to drive both the NV spins (~500 MHz) and the DNP agent spins (~2.37 GHz).
- NMR Drive: A separate resonant coil (Q ~140) was used to apply the Ï/2 pulse on the protons at ~3.606 MHz, achieving a proton Rabi frequency of ~4 kHz.
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Hyperpolarization (Overhauser DNP):
- Agent: TEMPOL (4-Hydroxy-TEMPO) molecular radicals were dissolved in the liquid sample (e.g., 20 mM in water).
- Process: Continuous microwave driving saturates the TEMPOL electronic spin transition (at 2.37 GHz), transferring thermal electron spin polarization to the nuclear spins of the sample molecules (protons).
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Detection Sequence (DNP-CASR):
- The full experiment alternates between the Overhauser DNP sequence (~2 x T1, typically 300 ms) and the FNP detection sequence (~4 x T2*, typically 200 ms).
- FNP Generation: A Ï/2 pulse is applied to the hyperpolarized proton spins.
- CASR Readout: The Free Nuclear Precession (FNP) signal is detected by the NV ensemble using the Coherently Averaged Synchronized Readout (CASR) magnetometry pulse sequence, which is based on XY8-6 dynamic decoupling subsequences synchronized to an external clock.
Commercial Applications
Section titled âCommercial ApplicationsâThe combination of femtomole sensitivity and picoliter volume selectivity makes this technology highly relevant for mass-limited analytical fields:
- Drug Discovery and Screening:
- High-throughput screening (HTS) of binding affinity for mass-limited chemical reactions (nanomole scale synthesis).
- Providing superior isomeric distinguishability compared to traditional mass spectrometry pipelines.
- Metabolomics and Cell Biology:
- Quantitative metabolic studies and real-time analysis of metabolic flux at the single-cell level, leveraging the picoliter volume selectivity.
- Analysis of small, precious biological samples where sample volume is severely restricted.
- Catalysis and Chemical Synthesis:
- High-throughput analysis of mass-limited chemical reactions, allowing rapid characterization of intermediates and products using minimal reagent quantities.
- Advanced Magnetic Resonance Imaging (MRI):
- Enabling NV-detected MRI techniques at the micrometer scale, potentially allowing studies of water diffusion and transport dynamics within cells and tissue.
- Quantum Sensing Technology:
- Development of next-generation, ultra-sensitive solid-state NMR sensors capable of operating at small bias fields (85 mT) while achieving high sensitivity typically associated with high-field inductive detectors.
View Original Abstract
Nuclear magnetic resonance (NMR) spectroscopy is a widely used tool for chemical analysis and molecular structure identification. Because it typically relies on the weak magnetic fields produced by a small thermal nuclear spin polarization, NMR suffers from poor molecule-number sensitivity compared to other analytical techniques. Recently, a new class of NMR sensors based on optically-probed nitrogen-vacancy (NV) quantum defects in diamond have allowed molecular spectroscopy from sample volumes several orders of magnitude smaller than the most sensitive inductive detectors. To date, however, NV-NMR spectrometers have only been able to observe signals from pure, highly concentrated samples. To overcome this limitation, we introduce a technique that combines picoliter-scale NV-NMR with fully integrated Overhauser dynamic nuclear polarization (DNP) to perform high-resolution spectroscopy on a variety of small molecules in dilute solution, with femtomole sensitivity. Our technique advances mass-limited NMR spectroscopy for drug and natural product discovery, catalysis research, and single cell studies.