High Temperature Superconducting (HTS) NMR Resonators

High Sensitivity NMR of Mass Limited Samples, Complex Mixtures and Structural Biology

Principal Investigator: Bill Brey
Program Director: Matthew Merritt

Solution 1H NMR has shown great success in understanding the structure and dynamics of molecules. Sensitivity, however, has limited the use of NMR in characterizing systems where samples are only available in limited quantities and where direct detection of 13C, 15N and other less abundant or less receptive isotopes is required. For typical 1H detection, NMR requires ~17 nanomoles of NMR active nuclei. As a result, NMR nuclei with a lower natural abundance (i.e. 13C, 2H, 15N) are even more challenging.  

We are developing high sensitivity probes and methodology for direct detection 13C, 2H, 15N NMR to address research problems in metabolomics, intrinsically disordered proteins (IDPs) and natural products. We anticipate achieving approximately a factor of two sensitivity improvement over conventional commercial cryoprobes, corresponding to a factor of two less sample. We are developing this probe for both metabolomics and protein structure. For metabolomics, this probe will be used for isotopomer analysis to assess metabolic changes. For protein structure NMR, we will optimize for efficient detection of 15N and 13C spins and be designed to exploit the recently described TROSY-based line narrowing effect at high field and the improved spectral dispersion of 13C chemical shifts.

  • Aim 1: Develop a 13C-optimized HTS probe for 1.1 GHz magnets that will utilize a new rectangular sample format to improve filling factor and sensitivity. The probe will be tested and demonstrated in the 1.1 GHz (25.9 T) Bruker Neo spectrometer being installed at the University of Georgia. The rectangular sample format allows for a sample volume similar to 5 mm probes together with the mass sensitivity of 3 mm probes. This aim builds on the Edison DBP and a separately funded project to develop a 13C-optimized probe for the University of Georgia.
  • Aim 2: Develop an HTS probe with superconducting receive and normal transmit coils. In spite of their superior sensitivity, applications of HTS probes have been limited. Normal metal probes typically achieve better lineshape and stronger B1 fields. A promising solution is to utilize a normal metal coil for transmit which will allow the HTS resonator to be optimized for lineshape. We will develop a hybrid probe with normal metal transmit and HTS receive which will have advantages from both technologies. We plan to target this “H-HTS” probe for 800 MHz and 3 mm samples.
  • Aim 3: Demonstrate improved resonator designs in HTS probes. In addition to developing two new HTS probes we propose to continue testing improvements in our current probes. We now have two promising designs to increase the current density in HTS resonators that can be tested and used in our existing 13C HTS probes.

Associated Driving Biomedical Projects (DBPs):

  • 13C NMR for improved metabolite identification; Art Edison, University of Georgia
  • Imaging Hepatic Gluconeogenesis with Hyperpolarized Dihydroxyacetone; Matt Merritt, University of Florida
  • RNA Recognition by Intrinsically Unstructured Proteins; Robert Silvers, Florida State University
  • In situ mapping energy landscapes of biological macromolecules and their complexes, Matt Eddy, University of Florida 

Associated Collaboration & Service Projects (CSPs):

  • Hyperpolarized 13C Metabolic MRI of Hypertrophic Cardiomyopathy; Roselle Abraham and Peder Larson, University of California, San Francisco
  • Metabolic Origins of Nonalcoholic Steatohepatitis (NASH), Shawn Burgess, University of Texas Southwestern
  • 13C NMR measurements of liver samples for development of unified model of hepatic metabolism; Stanislaw Deja, University of Texas Southwestern
  • 13C NMR measurements of liver samples for development of unified model of hepatic metabolism; John Griffith Jones, University of Coimbra, Portugal
  • Novel targeted anticancer agents from marine cyanobacteria; Hendrik Luesch, University of Florida
  • The Regulation of Hepatic Metabolic Zonation by the Diabetes Gene TCF7L2, Luke Norton, University of Texas, San Antonio
  • Metabolic origins of nonalcoholic steatohepatitis; Nishanth Sunny, University of Maryland

Technology Partnership Project (TPP):

To inquire about starting a collaboration including establishing a DBP, CSP, or TPP, please contact principal investigators for this TDP: https://nmrprobe.org/people/leadership/.