Detection of molecular transitions with nitrogen-vacancy centers and electron-spin labels
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2022-11-30 |
| Journal | npj Quantum Information |
| Authors | Carlos Munuera-Javaloy, Ricardo Puebla, Benjamin D’Anjou, Martin B. Plenio, J. Casanova |
| Institutions | Universität Ulm, University of the Basque Country |
| Citations | 9 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled “Executive Summary”This research presents a novel quantum sensing protocol utilizing a shallow Nitrogen-Vacancy (NV) center in diamond to detect single-molecule conformational changes at ambient conditions.
- Core Achievement: Demonstrated detection of inter-label coupling (g12) between two nitroxide electron-spin labels attached to a molecule, enabling the measurement of relative label positions (d12) down to the nanoscale.
- Methodology: A carefully engineered Double Electron-Electron Resonance (DEER) sequence, applying asymmetric Microwave (MW) pulses to the NV and Radiofrequency (RF) pulses to the labels, resolves small energy shifts in the NV spectrum.
- Tumbling Robustness: The protocol specifically targets the E0 energy-transition branch of the nitroxide labels, which exhibits excellent robustness against unavoidable molecular tumbling motion (simulated standard deviation σδ = 6.25°).
- Spectral Simplification: Using nitroxide labels containing distinct nitrogen isotopes (e.g., 14N and 15N) ensures orthogonal resonance frequencies, simplifying the inter-label interaction and eliminating complex flip-flop terms.
- Distance Extraction: Inter-label distance (d12) is extracted using a simple theoretical model combined with Bayesian inference (Markov Chain Monte Carlo), achieving high accuracy (inferred d12 = 3.54(25) nm vs. true d12 = 3.297 nm).
- Resource Exploitation: Counter-intuitively, the small residual effect of molecular tumbling is shown to be a resource, providing the necessary geometric variation to independently determine both the inter-label distance and the relative angle.
Technical Specifications
Section titled “Technical Specifications”| Parameter | Value | Unit | Context |
|---|---|---|---|
| NV Center Depth | 4 | nm | Proximity to diamond surface |
| NV Decoherence Time (T2*) | 20 | µs | Ambient conditions |
| Electron-Spin Label Relaxation (T1) | 4 | µs | Ambient conditions |
| Applied Magnetic Field (Bz) | 30 | mT | Used in simulations |
| Total Sequence Duration | 4.6 | µs | Total time for DEER protocol |
| Free Evolution Time (Tfree) | 1.3 | µs | Duration of phase accumulation stages |
| RF Rabi Frequency (ΩRF) | 2π x 250 | kHz | Applied to nitroxide labels |
| MW Rabi Frequency (ΩMW) | 31 x ΩRF | - | Applied to NV center |
| Inter-Label Coupling (g12) | ~2π x 1 | MHz | Used for d12 ≈ 3.3 nm |
| Simulated Inter-Label Distance (d12) | 3.297 | nm | Ground truth distance |
| Inferred Inter-Label Distance (d12) | 3.54(25) | nm | Result from Bayesian inference |
| Tumbling Standard Deviation (σδ) | 6.25 | ° | Gaussian distribution model |
| Required Measurements (Nm) | 2 x 104 | - | Ideal measurement accuracy |
| Required Measurements (Nm) | 5 x 105 | - | Estimated for imperfect NV detection efficiency |
Key Methodologies
Section titled “Key Methodologies”- System Setup: Employed a shallow NV center (4 nm depth) in diamond positioned near a target molecule labeled with two nitroxide electron-spin labels (free radicals).
- NV Initialization and Readout: The NV center is initialized and read out using laser light in the visible spectrum, removing thermal fluctuations from the measurement process.
- Modified DEER Sequence: The protocol uses two free-evolution stages (Tfree) separated by a driving stage consisting of 2N+1 continuous MW π-pulses on the NV center and a simultaneous, weaker RF π-pulse on the electron-spin labels.
- Asymmetric Driving: The MW field is resonant with the NV, while the RF field is resonant with the electronic transitions of the nitroxide labels, ensuring constructive phase accumulation and averaging out spurious NV-label interactions during irradiation.
- Targeting the E0 Branch: The RF frequency is tuned to the E0 energy-transition branch of the nitroxide labels, which is selected for its minimal dependence on the azimuth angle (θ), maximizing robustness against molecular motion.
- Isotopic Orthogonality: To simplify the inter-label interaction Hamiltonian and ensure clean spectral separation regardless of label orientation, distinct nitrogen isotopes (e.g., 14N and 15N) are used for the two nitroxide labels.
- Tumbling Modeling: Molecular tumbling is modeled as a random rigid rotation with a Gaussian distribution (σδ = 6.25°), and the resulting spectrum is obtained by averaging the NV response over these random orientations.
- Bayesian Inference: A simplified, accurate theoretical model of the tumbling-averaged spectrum is combined with Markov Chain Monte Carlo sampling to efficiently infer the posterior probability distribution of the inter-label distance (d12) and other unknown parameters.
Commercial Applications
Section titled “Commercial Applications”This technology provides a highly sensitive, nanoscale magnetic resonance platform suitable for studying molecular dynamics in complex environments, opening avenues in:
- Quantum Sensing and Metrology: Development of next-generation solid-state quantum sensors for high-resolution Electron Spin Resonance (ESR) and Nuclear Magnetic Resonance (NMR) spectroscopy at the single-molecule level.
- Structural Biology and Biochemistry: Real-time observation and characterization of conformational dynamics in individual proteins and macromolecules, crucial for understanding biological function, folding, and interaction mechanisms.
- Drug Discovery and Development: High-throughput screening and detailed analysis of drug-target binding kinetics and conformational changes induced by small molecules.
- Nanoscale Materials Characterization: Probing local magnetic environments and spin dynamics in complex soft matter systems and biological interfaces.
- Diamond Engineering: Advancing techniques for shallow NV implantation and surface functionalization necessary for robust coupling between quantum sensors and external molecular targets.
View Original Abstract
Abstract We present a protocol that detects molecular conformational changes with two nitroxide electron-spin labels and a nitrogen-vacancy (NV) center in diamond. More specifically, we demonstrate that the NV can detect energy shifts induced by the coupling between electron-spin labels. The protocol relies on the judicious application of microwave and radiofrequency pulses in a range of parameters that ensures stable nitroxide resonances. Furthermore, we demonstrate that our scheme is optimized by using nitroxides with distinct nitrogen isotopes. We develop a simple theoretical model that we combine with Bayesian inference techniques to demonstrate that our method enables the detection of conformational changes in ambient conditions including strong NV dephasing rates as a consequence of the diamond surface proximity and nitroxide thermalization mechanisms. Finally, we counter-intuitively show that with our method the small residual effect of random molecular tumbling becomes a resource that can be exploited to extract inter-label distances.
Tech Support
Section titled “Tech Support”Original Source
Section titled “Original Source”References
Section titled “References”- 1998 - Structure Elucidation by Modern NMR [Crossref]
- 1961 - The Principles of Nuclear Magnetism
- 2001 - Principles of pulsed electron paramagnetic resonance [Crossref]