Nuclear magnetic resonance microscopy using diamond quantum sensors - Project Summary: Nuclear magnetic resonance microscopy using diamond quantum sensors Acosta’s lab specializes in the emerging field of quantum sensing, broadly defined as the use of qubit systems to measure environmental parameters. They harness the optical and spin properties of nitrogen-vacancy (NV) color centers in diamond to image physical, chemical, and biological phenomena under a wide range of ambient conditions. Diamond quantum sensors offer exquisite sensitivity to their environment, while maintaining immunity to common sources of optical and spin instability, owing to protection from the diamond host matrix. A major part of the lab’s research is in device engineering, quantum optics, and spin physics. However, the motivation is to enable biochemistry applications. Acosta is most intrigued by the prospect for nuclear magnetic resonance (NMR) spectroscopy at the micrometer (sub-nanoliter) scale. The focus of this proposal is to dig deep into the (promising, but technically demanding) microscale NMR spectroscopy problem. NMR spectroscopy is a powerful analytical technique used widely in chemistry, biology, and pharmaceutical metabolomics research. This has been recognized by, for example, the six Nobel Prizes awarded for NMR methods development alone. Despite its impressive record, NMR spectroscopy is notoriously plagued by poor signal-to-noise ratio (SNR), particularly for small sample volumes. Miniature inductive coils have been developed to improve SNR for such samples, but their inherent discontinuities in magnetic susceptibility can lead to inadequate spectral resolution. An alternative strategy for small-volume NMR spectroscopy is to use a non-inductive detector. Various sensors have been pursued, but none yet meet the demanding requirements on spatial resolution, spectral resolution, and sensitivity needed for molecular analysis at the micrometer scale. Acosta’s goal is to develop a microfluidic NMR detection platform, based on diamond quantum sensors, that overcomes limitations of traditional NMR for small-sample analysis. If successful, the platform will address the acute need for non-invasive, label-free, chemically-specific techniques that can be integrated into hyphenated microfluidic assays. For example, in pharmaceutical drug discovery, detection methods which can identify and quantify metabolites in small fluid samples are essential for pharmacodynamics studies. Other applications include quantitation of natural products, trace contaminants, and combinatorial compounds. Acosta envisions two potential modalities: i) an NMR microscope that can probe metabolic processes in cell cultures or perform NMR molecular analysis in multiwell plates, and ii) a microfluidic NMR chip for hyphenated chemical analysis. To realize this goal, Acosta’s lab is pursuing: 1) developing new diamond quantum sensing protocols to improve sensitivity, 2) microfluidic integration strategies to improve spectral resolution, and 3) proof-of-principle applications in microfluidic metabolomics quantitation and single-cell NMR microscopy.
