The Future of NMR at the NHMFL

1. The Future of NMR at the NHMFL NMR Leading the Science Effort for Next-Generation NHMFL Magnets SCH 36 Tesla 1535 MHz ASC Materials Technology for Next-Generation Magnets HTS/LTS 30+ Tesla 1300+ MHz Materials Technology, Design, and Construction of the Next-Generation NHMFL Magnets MS&T NMR Program Mission • User Driven High Field Technology Development • User Driven High Field Application Development

2. Advantages of High Magnetic Fields coupled with High Homogeneity & High Magnet Stability • Altered Physical Phenomena at High Field, e.g. altered relaxation times in Magnetic Resonance • Different frequency regime, e.g. important for characterizing dynamics • Enhanced Sensitivity, e.g. can be greater than Bo4 • Enhanced Resolution, e.g. enhancements can increase with dimensionality of the spectra • Enhanced Spectral dispersion, leads to the possibility for developing 1H detection for biological solid state NMR • Changed Relative Magnitudes of Spin Interactions for Magnetic Resonance, e.g. leads to substantial resolution enhancements, such as TROSY; leads to greatly improved resolution for quadrupolar nuclei • Increased Magnetic Susceptibility, e.g. enhanced Functional MRI and contrast; improved alignment of diamagnetic, paramagnetic molecules Many of these Factors Combine in a Multiplicative Fashion for NMR and MRI

3. Resolution & Sensitivity from Quadrupolar Nuclei Gan et al. (2008) JMR 191:135 Sefzik et al. (2007) Chem. Phys. Lett. »» Sensitivity Enhancement  ~Bo4

4. Synergy in Developing 36 T SCH & 30+ T HTS/LTS 36 T SCH 30+ T HTS/LTS • Access to high fields for NMR after 2013. • Will need the technology developed on the SCH such as the field frequency lock • Development of probes for solution and solid state NMR and for MRI will be based on experience from the SCH • Anticipating 8000 hours of oper-ation and all of the time for NMR and MRI • Development of routine NMR and MRI usage for those activities that benefit the most from High Field • Access to high fields for NMR and MRI soon (2013). • Development of a sophisticated field frequency lock • Development of probes for solution and solid state NMR and for MRI • Temporal stability and homogen-eity of 0.1 to 1.0 ppm - potentially some experiments can be performed at 0.01 ppm • Anticipating 1000 hours of oper-ation per year and 50% of this time for NMR and MRI • Most run time will be limited to an 8 hour block • Demonstrations of Materials and Biological Science

5. Time to echo   1st Generation 2nd Generation 3rd Generation Realizing the Science: Stabilization of the Resistive Keck Magnet at 25 Tesla Significant Echo Times have been achieved opening the door for the first time to a broad range of NMR and MRI experiments J. Schiano, PSU M. Li, PSU - Recently Defended Ph.D. W. Brey, NHMFL K. Shetty, NHMFL 90x 180x 80 70 60 NMR Phase Fluctuations [°] 50 40 30 SCH Program Development SCH DESIGN GOAL 20 10 0 0 4 8 12 16 20 Time to Echo [ms]

6. Realizing the Science: HEteroNuclear PhasE Correction (HENPEC) Spectroscopy • Using the single sharp line of 2H as a phase reference can enhance the resolution of the spectra by nearly two orders of magnitude. • The 25 Tesla (1066 MHz) Resistive Magnet at the NHMFL Gan et al. (2008) J. Magn. Reson. 191:135-140

7. Realizing the Science: RF Probe Development for the 36 T SCH • Funded in the SCH Magnet Construction Phase Grant - High Resolution MAS probe for solution spectroscopy with single axis pulsed field gradient: 1H observe, 13C decouple and 2H lock -10° to +50°C VT range - 5 mm 1H observe 13C indirect probe with 2H lock and 3 axis pulsed field gradients -10° to +50°C VT range - CP MAS Probe for broadband observe and 1H decouple with 2.5 mm rotor - 50° to +100°C VT range - MAS single frequency probe with wide tuning range for 4 mm sample rotor - 10° to +50°C VT range - broadband observe (15N - 31P), 1H decouple (Low-E coil) aligned sample probe -10° to +50°C VT range • To be funded (?) through the SCH Console MRI Proposal - Dielectric resonators for 1H microimaging - this is a technology that will take great advantage of higher frequencies - a collaboration with Andrew Webb at Penn. State and Leiden Univ. - A LHe cooled dipping probe to examine the quadrupolar sites in metalloproteins - a collaboration between Peter Gor’kov and Jesse Sears at PNNL - MicroMAS (1.6 mm) triple resonance solid state NMR probe with temperature capability down to 200K - a collaboration between Bill Brey, Peter Gor’kov and Kurt Zilm at Yale

8. State of the Art in HTS/LTS NMR Magnets • Y. Iwasa, MIT 700 MHz (100 MHz double pancake Bi2223 tape) A number of significant challenges in the drive toward high homogeneity and high stability have been described in Iwasa’s publications. For instance, the screening current induced fields generated by the double pancake HTS coil appears to be primarily responsible for the non-linear behavior of the a Z1 room temperature shim Hahn et al., (2009) IEEE Trans. Appl. Supercond. 19:2285

9. State of the Art in HTS/LTS NMR Magnets • H. Maeda, RIKEN & Yokohama Univ. 500 MHz (76 MHz double pancake Bi2223 tape) • Significant problems with drift (some of it due to a poor power supply) and homogeneity (a degra-dation of a ppb in 74 hours) were observed. • The 10 hour 3D HNCACB spectrum is an awesome achievement. LTS/HTS LTS Yanagisawa et al., (2010) JMR 203:274-282

10. HTS/LTS NMR Magnets: Scientific Frontiers • Structural biology is shifting toward the study of protein complexes - most proteins and nucleic acids function as complexes in the cell - NMR provides an opportunity to characterize these complexes in a native-like environment and higher fields will permit the characterization of larger complexes and complexes that bind more weakly. • Characterizing proteins in a native-like environment is becoming increasingly important especially for proteins that occur in a heterogeneous environment - protein structure is the result of protein-protein interactions as well as protein-environment interactions. • Characterizing materials for anodes and cathodes in functioning model batteries and synthetic membranes for fuel cells as well as the characterization of catalytic surfaces will be greatly enhanced through expanded access to the quadrupolar nuclei of the Periodic Table. • Characterizing complex mixtures as in metabolomics will greatly benefit from the increased dispersion and will not be signifiantly hindered by small sample size.

11. HTS/LTS NMR Magnets: Thoughts on a Roadmap • Partnering with industry - it is unlikely that the NHMFL will design and construct the entire HTS/LTS magnet. It will be important to develop a partnership, most likely with Agilent. • Funding the Design and Construction of the Magnet - an effort will have to be made to lay the ground work for submitting a proposal for funding to NIH and or DOE. This needs to be an NHMFL-wide effort. • Workshop on HTS/LTS Materials, Magnets and Potential Science - The NHMFL will develop a workshop, probably to be held in Washington DC for good NSF, NIH and DOE participation.