Prospects of single-cell nuclear magnetic resonance spectroscopy with quantum sensors.

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.

Imaging local diffusion in microstructures using NV-based pulsed field gradient NMR.

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.

The Role of Electrolytes in the Relaxation of Near-Surface Spin Defects in Diamond.

Quantum sensing with spin defects in diamond, such as the nitrogen vacancy (NV) center, enables the detection of various chemical species on the nanoscale. Molecules or ions with unpaired electronic spins are typically probed by their influence on the NV center's spin relaxation. Whereas it is well-known that paramagnetic ions reduce the NV center's relaxation time (T1), here we report on the opposite effect for diamagnetic ions. We demonstrate that millimolar concentrations of aqueous diamagnetic electrolyte solutions increase the T1 time of near-surface NV center ensembles compared to pure water. To elucidate the underlying mechanism of this surprising effect, single and double quantum NV experiments are performed, which indicate a reduction of magnetic and electric noise in the presence of diamagnetic electrolytes. In combination with ab initio simulations, we propose that a change in the interfacial band bending due to the formation of an electric double layer leads to a stabilization of fluctuating charges at the interface of an oxidized diamond. This work not only helps to understand noise sources in quantum systems but could also broaden the application space of quantum sensors toward electrolyte sensing in cell biology, neuroscience, and electrochemistry.

Advances in nano- and microscale NMR spectroscopy using diamond quantum sensors.

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- and microscale NMR spectroscopy. Furthermore, we highlight possible future applications of this novel technology ranging from energy research, materials science, to single-cell biology, and discuss the associated challenges of these rapidly developing NMR sensors.

Surface NMR using quantum sensors in diamond.

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.