Hyperpolarization-Enhanced NMR Spectroscopy with Femtomole Sensitivity Using Quantum Defects in Diamond

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 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.