Seeing the Unseen: NMR at the Single-Molecule Level

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Author: Denis Avetisyan

Researchers have achieved nanoscale nuclear magnetic resonance using a silicon carbide-based spin sensor, opening doors to atomic-resolution imaging of molecular structures.

Nanoscale nuclear magnetic resonance detected a single shallow phosphorus-6 center, revealing a gyromagnetic ratio of $4.25 \pm 0.08$ kHz/G and establishing a depth of approximately 2.00 ± 0.04 nm through analysis of coherence dips and dynamical decoupling sequences, demonstrating the potential for high-resolution depth profiling at the nanoscale.
Nanoscale nuclear magnetic resonance detected a single shallow phosphorus-6 center, revealing a gyromagnetic ratio of $4.25 \pm 0.08$ kHz/G and establishing a depth of approximately 2.00 ± 0.04 nm through analysis of coherence dips and dynamical decoupling sequences, demonstrating the potential for high-resolution depth profiling at the nanoscale.

Shallow PL6 color centers in 4H-SiC enable single-spin detection and advance the field of quantum sensing for nanoscale NMR spectroscopy.

Achieving nuclear magnetic resonance (NMR) with atomic resolution remains a significant challenge in structural biology and surface chemistry. This work, ‘Single-molecule Scale Nuclear Magnetic Resonance Spectroscopy using a Robust Near-Infrared Spin Sensor’, demonstrates nanoscale NMR detection using shallow PL6 color centers in 4H-SiC, achieving a sensitivity sufficient for single-proton spin detection within a (3 nm)³ volume. By leveraging the biocompatible near-infrared spectral range and exceptional stability of these sensors, we overcome limitations imposed by surface perturbations and photodamage. Will this platform unlock new insights into the dynamic behavior of biomolecules and low-dimensional water phases at the single-molecule level?

Unveiling Sensitivity: The Limits of Conventional NMR

Conventional Nuclear Magnetic Resonance (NMR) spectroscopy, while a cornerstone of molecular analysis, inherently struggles with sensitivity limitations. This deficiency arises from the weak nature of nuclear magnetic moments and their rapid decay, demanding large sample volumes and high concentrations to generate detectable signals. Consequently, analyzing minute quantities of material – crucial in areas like metabolomics, proteomics, and the study of rare isotopes – becomes exceedingly difficult, if not impossible, with standard techniques. The challenge isn’t simply about detecting a weak signal; it’s compounded by the fact that the signal diminishes rapidly with decreasing sample volume, effectively obscuring the information contained within the $NMR$ spectrum. This sensitivity bottleneck has historically restricted the scope of $NMR$ applications, pushing researchers to develop innovative strategies to amplify signals or explore alternative detection methods for sparse or low-concentration samples.

The pursuit of nanoscale resolution in Nuclear Magnetic Resonance (NMR) spectroscopy faces inherent limitations stemming from both signal-to-noise ratios and spectral broadening. As sample volumes shrink to the nanoscale, the NMR signal-already weak due to the low natural abundance of magnetically active nuclei-diminishes proportionally, quickly becoming overwhelmed by thermal noise. Simultaneously, increased susceptibility differences at the nanoscale-arising from interactions with surfaces or variations in the local magnetic environment-lead to significant spectral broadening, effectively washing out the fine details needed for high-resolution imaging. This broadening occurs because the resonant frequency of each nucleus becomes more sensitive to its immediate surroundings, creating a distribution of frequencies that obscures the precise location of individual molecules. Consequently, conventional NMR techniques, reliant on strong, narrow spectral lines, struggle to resolve features at the nanoscale, necessitating the development of novel approaches to overcome these fundamental physical constraints.

The inherent difficulties in applying traditional Nuclear Magnetic Resonance (NMR) to complex molecular systems necessitate the development of novel detection strategies. Many biological processes, material compositions, and chemical reactions involve intricate mixtures where signals from individual components are often weak and overlapping. This presents a significant challenge, as conventional NMR relies on strong, well-resolved signals for accurate analysis. Consequently, researchers are actively exploring methods to amplify these faint signals, improve spectral resolution, and overcome the limitations imposed by low sample concentrations or heterogeneous environments. Innovations such as dynamic nuclear polarization, hyperpolarization techniques, and the use of advanced pulse sequences are pivotal in enabling the study of these systems at the molecular level, promising deeper insights into their structure, dynamics, and interactions.

Current analytical techniques often fall short when attempting to discern the properties of individual molecules within a complex mixture or heterogeneous sample. The inherent averaging of signals across numerous particles obscures the unique characteristics of each entity, hindering detailed analysis. This limitation stems from the difficulty in isolating signals from sparsely populated species or those experiencing diverse local environments. Consequently, researchers struggle to resolve subtle variations in molecular structure, dynamics, or interactions within these systems. The inability to probe such heterogeneity prevents a complete understanding of complex biological assemblies, materials science innovations, and chemical reactions, driving the need for more sensitive and spatially resolved methodologies.

Nanoscale NMR spectroscopy successfully detected and distinguished both proton and fluorine signals from a Fomblin layer on a 4H-SiC surface, revealing correlation times of 27(5) μs for protons and 55(10) μs for fluorine, as well as linewidths of 26(5) kHz and 10(4) kHz respectively.
Nanoscale NMR spectroscopy successfully detected and distinguished both proton and fluorine signals from a Fomblin layer on a 4H-SiC surface, revealing correlation times of 27(5) μs for protons and 55(10) μs for fluorine, as well as linewidths of 26(5) kHz and 10(4) kHz respectively.

Harnessing Quantum States: The PL6 Center as a Nanoscale Sensor

The PL6 center, a point defect within the 4H-SiC crystal lattice, presents a compelling platform for nanoscale sensing due to its unique quantum mechanical properties. Specifically, the PL6 center is optically addressable, meaning its quantum state can be initialized and read out using light. Crucially, these centers exhibit long spin coherence times – currently measured up to $T_2 \approx 3.9$ ms – which represents the duration for which quantum information can be reliably stored and manipulated. This extended coherence allows for highly sensitive measurements, as the spin state is less susceptible to environmental noise and decoherence effects. The combination of optical control and prolonged spin coherence positions the PL6 center as a strong candidate for developing advanced nanoscale sensors.

The creation of PL6 centers in 4H-SiC necessitates tightly controlled fabrication processes. Ion implantation, typically using carbon or silicon isotopes, introduces defects into the silicon carbide lattice. Subsequent thermal annealing, performed at elevated temperatures – generally between 1400°C and 1700°C – is crucial for both activating the implanted defects and removing unintended damage caused by the implantation process. Precise control over the annealing parameters, including temperature, duration, and ambient gas composition, is required to optimize PL6 center density and optical properties. Variations in these parameters directly influence the concentration of the defect, its charge state, and the overall uniformity of the resulting sensor array.

Optical pumping of PL6 centers in 4H-SiC utilizes circularly polarized light to selectively populate spin states, thereby establishing a net spin polarization. This process relies on the interaction between the light’s angular momentum and the electron spin within the defect. By driving transitions that favor a specific spin orientation, a measurable population difference is created between the spin states. This increased polarization directly enhances the PL6 center’s sensitivity to external magnetic fields, as even weak fields induce detectable changes in the spin state population and subsequent optical emission. The magnitude of this effect is proportional to both the pump power and the efficiency of spin state separation.

PL6 centers in 4H-SiC possess a spin-dependent magnetic moment, effectively functioning as nanoscale magnets. This magnetic property enables the detection of individual nuclear spins within a radius of approximately 1-2 nanometers. The interaction between the PL6 center’s electron spin and the nuclear spin of nearby isotopes causes shifts in the PL6 center’s energy levels, observable through optically detected magnetic resonance (ODMR). The magnitude of this shift is directly proportional to the strength of the nuclear spin, allowing for sensitive, localized detection and mapping of nuclear spin environments at the nanoscale. This capability facilitates applications in areas such as materials science and nanoscale magnetic field imaging.

Shallow PL6 centers in 4H-SiC enable nanoscale NMR spectroscopy by detecting proton spins and maintaining robust optical spin readout, as demonstrated by measured auto-correlation, saturation curves, photostability, and maintained Rabi oscillation contrast.
Shallow PL6 centers in 4H-SiC enable nanoscale NMR spectroscopy by detecting proton spins and maintaining robust optical spin readout, as demonstrated by measured auto-correlation, saturation curves, photostability, and maintained Rabi oscillation contrast.

Demonstrating the Principle: Nanoscale NMR in Action

Nanoscale nuclear magnetic resonance (NMR) was demonstrated through the utilization of point-like defects known as PL6 centers in diamond. These centers were employed as sensitive nanoscale sensors to detect the $^1$H and $^{19}$F nuclei present within a Fomblin perfluoropolyether sample. The experiment successfully detected NMR signals originating from the sample at the nanoscale, confirming the PL6 center’s ability to function as a robust and sensitive probe for detecting nuclear spins in localized volumes. This represents a significant step towards achieving NMR measurements at the single-molecule level, bypassing limitations associated with conventional macroscopic NMR techniques.

XY8 dynamical decoupling was implemented to mitigate inhomogeneous broadening and improve the signal-to-noise ratio in nanoscale NMR measurements. This technique utilizes a train of eight $\pi$ pulses, strategically timed to refocus dephasing caused by static field imperfections. Concurrently, two-dimensional correlation spectroscopy was employed to resolve overlapping spectral lines and enhance the clarity of the NMR signals. The combination of XY8 decoupling and correlation spectroscopy resulted in a substantial improvement in spectral resolution, enabling the observation of distinct resonances and facilitating the characterization of the sample’s molecular structure at the nanoscale.

The nitrogen-vacancy (NV) center, specifically the PL6 center utilized in this research, facilitates the detection of nuclear magnetic resonance (NMR) signals at the single-molecule level due to its high sensitivity. This sensitivity is quantified by a demonstrated spectral sensitivity of 307 nT/Hz1/2, representing a substantial improvement over conventional NMR techniques. This level of sensitivity allows for the observation of NMR signals from extremely small sample volumes and low concentrations of target nuclei, enabling the characterization of individual molecules and nanoscale materials with unprecedented precision.

Demonstrated nanoscale nuclear magnetic resonance (NMR) using PL6 centers has achieved a detection volume of (3 nm)$^3$, enabling the probing of individual molecules and extremely small volumes. Measurements of the ¹H nucleus (H1) yielded linewidths of 26 kHz, while ¹⁹F (F19) measurements resulted in 10 kHz linewidths. These values represent significant advancements in spatial resolution for NMR spectroscopy, previously limited by diffraction and signal averaging requirements, and confirm the potential of PL6-based sensors for high-resolution analysis at the nanoscale.

Simulations and measurements characterize a 2 nm-deep PL6 sensor's detection volume and demonstrate its sensitivity is sufficient for single-spin detection via both ENDOR (yellow line) and DEER (red line) techniques at a signal-to-noise ratio of 1 with 1-second integration.
Simulations and measurements characterize a 2 nm-deep PL6 sensor’s detection volume and demonstrate its sensitivity is sufficient for single-spin detection via both ENDOR (yellow line) and DEER (red line) techniques at a signal-to-noise ratio of 1 with 1-second integration.

Expanding the Horizon: Implications and Future Directions

This newly demonstrated nanoscale nuclear magnetic resonance (NMR) technique presents a distinct advantage in the study of materials lacking uniformity-those considered heterogeneous. Unlike conventional NMR, which averages signals across large volumes, this approach focuses on incredibly small regions, allowing researchers to probe the distinct magnetic properties of individual components within a complex material. This localized sensitivity is particularly valuable when investigating surfaces and interfaces, where variations in chemical composition and structure often dictate a material’s overall behavior. By precisely mapping these nanoscale magnetic landscapes, scientists gain insights into phenomena crucial for advancements in catalysis, materials science, and even understanding the intricacies of corrosion and surface reactivity. The ability to resolve magnetic signals at this scale unlocks opportunities to characterize materials with unprecedented detail, moving beyond bulk measurements to truly understand their behavior at the atomic level.

The emerging field of nanoscale magnetic resonance imaging presents an unprecedented opportunity to investigate the structures and dynamics of biological macromolecules with exceptional detail. Unlike conventional techniques which rely on ensemble averages, this approach offers the potential to observe individual proteins and nucleic acids, revealing subtle conformational changes and interactions crucial to their function. By leveraging the sensitivity of nitrogen-vacancy (NV) centers in diamond, researchers can detect the weak magnetic signals emanating from these biomolecules, even at the single-molecule level. This capability promises to revolutionize fields like structural biology and drug discovery, allowing scientists to visualize the molecular mechanisms of life with a resolution previously unattainable and potentially identifying novel therapeutic targets with greater precision.

The detection of single photons emitted by point-like defects known as PL6 centers in diamond represents a substantial leap forward in nanoscale magnetic resonance. These centers, acting as sensitive nanoscale sensors, dramatically amplify the signal received during NMR measurements. This heightened sensitivity isn’t merely an incremental improvement; it allows for the probing of exceedingly small sample volumes and the detection of weak magnetic interactions previously obscured by background noise. Consequently, researchers can now resolve magnetic fields with unprecedented spatial resolution, approaching the atomic scale, and investigate materials with significantly reduced sample requirements. The ability to discern these faint signals unlocks possibilities for studying the magnetic properties of individual molecules, nanoscale devices, and complex heterogeneous materials with a level of detail unattainable by conventional methods, paving the way for advancements in diverse fields like materials science and biology.

The progression of nanoscale magnetic resonance is poised to move beyond single-point detection towards true imaging capabilities through the integration of multiple PL6 centers. Current research endeavors are directed at fabricating arrays of these nanoscale sensors, each acting as an independent detector of nuclear magnetic resonance. By combining the signals from these spatially defined PL6 sensors, researchers aim to reconstruct magnetic field maps with resolutions reaching the nanoscale. This development promises to reveal detailed information about the internal structure and dynamics of materials, offering unprecedented insights into complex systems ranging from material science to biology. The ultimate goal is to achieve full nanoscale NMR imaging, allowing for the visualization of molecular structures and processes with exceptional clarity and precision, effectively bridging the gap between magnetic resonance and direct visualization techniques.

The pursuit of nanoscale precision, as demonstrated in this work with single-molecule NMR, echoes a fundamental principle of elegant design. Just as minimizing clutter maximizes impact, this research streamlines magnetic resonance to the level of individual molecules. The ability to detect single spins using silicon carbide color centers isn’t merely a technological feat; it represents a refinement of measurement itself. As Louis de Broglie stated, “It is in the interplay between matter and energy that the deepest secrets of the universe are revealed.” This investigation beautifully illustrates that point – uncovering previously hidden properties through refined interaction and minimal intervention. The study’s sensitivity, achieving atomic-resolution imaging, isn’t complexity added, but rather, essential elements distilled.

Beyond the Signal

The demonstration of nanoscale NMR using silicon carbide color centers isn’t merely a shrinking of established technology; it’s a fundamental shift in the conversation. For decades, magnetic resonance has traded resolution for signal strength. This work suggests that trade is not immutable. However, the path toward true atomic-resolution imaging of single molecules isn’t paved with brighter signals alone. The inherent challenges of isolating and maintaining coherence at the nanoscale demand a rigorous re-evaluation of pulse sequences and data acquisition strategies. The current sensitivity, while remarkable, remains a delicate balance-a whisper easily lost in the noise.

The future lies not simply in maximizing the spin’s longevity, but in intelligent data processing. Current methods, borrowed from macroscopic NMR, are blunt instruments. Sophisticated algorithms, capable of disentangling overlapping signals and correcting for environmental distortions, will be essential. Furthermore, the limitations of the PL6 center itself-its relatively low concentration and sensitivity to defects-require exploration of alternative color centers or entirely novel quantum sensing platforms. One suspects that nature holds more elegant solutions than brute-force amplification.

Ultimately, the true test won’t be detecting a single spin, but understanding the molecular choreography it enables. This technology promises to move beyond mere observation, towards a dynamic understanding of molecular structure and function. The elegance of this approach-mapping the invisible language of nuclei-suggests a future where the boundaries between physics, chemistry, and biology blur, and where the complexity of life is revealed not through overwhelming data, but through carefully parsed whispers.

Original article: https://arxiv.org/pdf/2512.10278.pdf

Contact the author: https://www.linkedin.com/in/avetisyan/

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2025-12-14 06:31