Nuclear magnetic resonance (NMR) and electron spin resonance (ESR) methods are indispensable techniques that utilize the spin of particles to probe matter, with applications in various disciplines, including fundamental physics, chemistry, biology, and medicine. Despite their versatility, the technique's sensitivity, particularly for NMR, is intrinsically low, which typically limits the detection of magnetic resonance (MR) signals to macroscopic sample volumes. In recent years, atom-sized magnetic field quantum sensors based on nitrogen-vacancy (NV) centers in diamond paved the way to detect MR signals at the micro- and nanoscale, even down to a single spin. In this perspective, we offer an overview of the most promising directions in which this evolving technology is developing. Significant advancements are anticipated in the life sciences, including applications in single molecule and cell studies, lab-on-a-chip analytics, and the detection of radicals or ions. Similarly, NV-MR is expected to have a substantial impact on various areas in the materials research, such as surface science, catalysis, 2D materials, thin films, materials under extreme conditions, and quantum technologies.

Single-cell analysis can unravel functional heterogeneity within cell populations otherwise obscured by ensemble measurements. However, noninvasive techniques that probe chemical entities and their dynamics are still lacking. This challenge could be overcome by novel sensors based on nitrogen-vacancy (NV) centers in diamond, which enable nuclear magnetic resonance (NMR) spectroscopy on unprecedented sample volumes. In this perspective, we briefly introduce NV-based quantum sensing and review the progress made in microscale NV-NMR spectroscopy. Last, we discuss approaches to enhance the sensitivity of NV ensemble magnetometers to detect biologically relevant concentrations and provide a roadmap toward their application in single-cell analysis.

Understanding diffusion in microstructures plays a crucial role in many scientific fields, including neuroscience, medicine, or energy research. While magnetic resonance (MR) methods are the gold standard for diffusion measurements, spatial encoding in MR imaging has limitations. Here, we introduce nitrogen-vacancy (NV) center-based nuclear MR (NMR) spectroscopy as a powerful tool to probe diffusion within microscopic sample volumes. We have developed an experimental scheme that combines pulsed gradient spin echo (PGSE) with optically detected NV-NMR spectroscopy, allowing local quantification of molecular diffusion and flow. We demonstrate correlated optical imaging with spatially resolved PGSE NV-NMR experiments probing anisotropic water diffusion within an individual model microstructure. Our optically detected PGSE NV-NMR technique opens up prospects for extending the current capabilities of investigating diffusion processes with the future potential of probing single cells, tissue microstructures, or ion mobility in thin film materials for battery applications.

Negatively-charged boron vacancy centers (V-B(-)) in hexagonal Boron Nitride (hBN) are attracting increasing interest since they represent optically-addressable qubits in a van der Waals material. In particular, these spin defects have shown promise as sensors for temperature, pressure, and static magnetic fields. However, their short spin coherence time limits their scope for quantum technology. Here, we apply dynamical decoupling techniques to suppress magnetic noise and extend the spin coherence time by two orders of magni-tude, approaching the fundamental T-1 relaxation limit. Based on this improvement, we demonstrate advanced spin control and a set of quantum sensing protocols to detect radiofrequency signals with sub-Hz resolution. The corresponding sensitivity is benchmarked against that of state-of-the-art NV-diamond quantum sensors. This work lays the foundation for nanoscale sensing using spin defects in an exfoliable material and opens a promising path to quantum sensors and quantum networks integrated into ultra-thin structures.

Quantum sensing with spin defectsin diamond, such asthe nitrogenvacancy (NV) center, enables the detection of various chemical specieson the nanoscale. Molecules or ions with unpaired electronic spinsare typically probed by their influence on the NV center'sspin relaxation. Whereas it is well-known that paramagnetic ions reducethe NV center's relaxation time (T (1)), here we report on the opposite effect for diamagnetic ions. Wedemonstrate that millimolar concentrations of aqueous diamagneticelectrolyte solutions increase the T (1) timeof near-surface NV center ensembles compared to pure water. To elucidatethe underlying mechanism of this surprising effect, single and doublequantum NV experiments are performed, which indicate a reduction ofmagnetic and electric noise in the presence of diamagnetic electrolytes.In combination with ab initio simulations, we proposethat a change in the interfacial band bending due to the formationof an electric double layer leads to a stabilization of fluctuatingcharges at the interface of an oxidized diamond. This work not onlyhelps to understand noise sources in quantum systems but could alsobroaden the application space of quantum sensors toward electrolytesensing in cell biology, neuroscience, and electrochemistry.

Atomic-scale magnetic field sensors based on nitrogen vacancy (NV) defects in diamonds are an exciting platform for nanoscale nuclear magnetic resonance (NMR) spectroscopy. The detection of NMR signals from a few zeptoliters to single molecules or even single nuclear spins has been demonstrated using NV centers close to the diamond surface. However, fast molecular diffusion of sample molecules in and out of the nanoscale detection volumes impedes their detection and limits current experiments to solid-state or highly viscous samples. Here, we show that restricting diffusion by confinement enables nanoscale NMR spectroscopy of liquid samples. Our approach uses metal-organic frameworks (MOF) with angstrom-sized pores on a diamond chip to trap sample molecules near the NV centers. This enables the detection of NMR signals from a liquid sample, which would not be detectable without confinement. These results set the route for nanoscale liquid-phase NMR with high spectral resolution.

Lab-on-a-chip (LOC) applications have emerged as invaluable physical and life sciences tools. The advantages stem from advanced system miniaturization, thus, requiring far less sample volume while allowing for complex functionality, increased reproducibility, and high throughput. However, LOC applications necessitate extensive sensor miniaturization to leverage these inherent advantages fully. Atom-sized quantum sensors are highly promising to bridge this gap and have enabled measurements of temperature, electric and magnetic fields on the nano- to microscale. Nevertheless, the technical complexity of both disciplines has so far impeded an uncompromising combination of LOC systems and quantum sensors. Here, we present a fully integrated microfluidic platform for solid-state spin quantum sensors, like the nitrogen-vacancy (NV) center in diamond. Our platform fulfills all technical requirements, such as fast spin manipulation, enabling full quantum sensing capabilities, biocompatibility, and easy adaptability to arbitrary channel and chip geometries. To illustrate the vast potential of quantum sensors in LOC systems, we demonstrate various NV center-based sensing modalities for chemical analysis in our microfluidic platform, ranging from paramagnetic ion detection to high-resolution microscale NV-NMR. Consequently, our work opens the door for novel chemical analysis capabilities within LOC devices with applications in electrochemistry, high-throughput reaction screening, bioanalytics, organ-on-a-chip, or single-cell studies.

Quantum technologies have seen a rapid developmental surge over the last couple of years. Though often overshadowed by quantum computation, quantum sensors show tremendous potential for widespread applications in chemistry and biology. One system stands out in particular: the nitrogen-vacancy (NV) center in diamond, an atomic-sized sensor allowing the detection of nuclear magnetic resonance (NMR) signals at unprecedented length scales down to a single proton. In this article, we review the fundamentals of NV center-based quantum sensing and its distinct impact on nano- to microscale NMR spectroscopy. Furthermore, we highlight and discuss possible future applications of this novel technology ranging from energy research, material science, or single-cell biology, but also associated challenges of these rapidly developing NMR sensors.

Nitrogen-vacancy (N-V) diamonds have attracted keen interest for nanoscale sensing and spin manipulation. In particular, the nonequilibrium electron spin polarization after optical excitation of single N-V centers has successfully been transferred to nuclear spin baths in the surrounding of defects. However, these experiments need to be extended to N-V ensembles that have promising practical applications in the hyperpolarization of bulk sample volumes for NMR signal enhancement. Here, we use a dense, shallow ensemble of N-V centers to demonstrate polarization transfer to nuclear spins in a well-defined composite diamond sample system. This allows us to address three different types of nuclear spins in different positions with respect to the N-V polarization source: from the close proximity of C-13 inside the diamond lattice to the self-assembled molecular system consisting of H-1 and F-19 spins outside the diamond and over multiple interfaces. We show that ensemble N-V experiments face problems different from single N-V experiments. In particular, using spinlock pulses, the inhomogeneously broadened electron spin resonance line of the N-V ensemble limits the minimal resonance linewidth with which the transfer protocol can occur. Furthermore, we compare the N-V spin-polarization losses and polarization transfer rates to the different nuclear baths and discuss the role of spin diffusion as detrimentally affecting the direct observation of nuclear polarization buildup within the detection volume of nanoscale N-V-NMR experiments.

NMR is a noninvasive, molecular-level spectroscopic technique widely used for chemical characterization. However, it lacks the sensitivity to probe the small number of spins at surfaces and interfaces. Here, we use nitrogen vacancy (NV) centers in diamond as quantum sensors to optically detect NMR signals from chemically modified thin films. To demonstrate the method's capabilities, aluminum oxide layers, common supports in catalysis and materials science, are prepared by atomic layer deposition and are subsequently functionalized by phosphonate chemistry to form self-assembled monolayers. The surface NV-NMR technique detects spatially resolved NMR signals from the monolayer, indicates chemical binding, and quantifies molecular coverage. In addition, it can monitor in real time the formation kinetics at the solid-liquid interface. With our approach, we show that NV quantum sensors are a surface-sensitive NMR tool with femtomole sensitivity for in situ analysis in catalysis, materials, and biological research.