Person:

Bucher, Dominik

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 the state-of-the-art of mass-limited NMR spectroscopy, opening the door to new applications at the picoliter-scale in drug and natural product discovery, catalysis research, and single cell studies.

Quantum systems that consist of solid-state electronic spins can be sensitive detectors of nuclear magnetic resonance (NMR) signals, particularly from very small samples. For example, nitrogen–vacancy centres in diamond have been used to record NMR signals from nanometre-scale samples1,2,3, with sensitivity sufficient to detect the magnetic field produced by a single protein4. However, the best reported spectral resolution for NMR of molecules using nitrogen–vacancy centres is about 100 hertz5. This is insufficient to resolve the key spectral identifiers of molecular structure that are critical to NMR applications in chemistry, structural biology and materials research, such as scalar couplings (which require a resolution of less than ten hertz6) and small chemical shifts (which require a resolution of around one part per million of the nuclear Larmor frequency). Conventional, inductively detected NMR can provide the necessary high spectral resolution, but its limited sensitivity typically requires millimetre-scale samples, precluding applications that involve smaller samples, such as picolitre-volume chemical analysis or correlated optical and NMR microscopy. Here we demonstrate a measurement technique that uses a solid-state spin sensor (a magnetometer) consisting of an ensemble of nitrogen–vacancy centres in combination with a narrowband synchronized readout protocol7,8,9 to obtain NMR spectral resolution of about one hertz. We use this technique to observe NMR scalar couplings in a micrometre-scale sample volume of approximately ten picolitres. We also use the ensemble of nitrogen–vacancy centres to apply NMR to thermally polarized nuclear spins and resolve chemical-shift spectra from small molecules. Our technique enables analytical NMR spectroscopy at the scale of single cells.