Higher Magnetic Fields are on the Horizon:

What Science will be Facilitated?

What is the Technology that will be make this

Possible?

When will all of this Happen?

Today: 23.5 T (1 GHz 1H NMR)

MagSci Challenge: ≈30 T by ≈2020

High Temperature Superconductors for High Fields

have become a viable technology

Why New Materials are Needed for

the Next Generation of Magnets

• Low T Superconductors

• High T SuperconductorsCeramics

• Wire vs. Tape

• But the potential!!

Jc, Critical Current Density, is a function of Field, Temperature, Strain, Mechanical Strength and Wire Piece Length.

Even the Nb3Sn is a sophisticated material the result of a

complicated process

• Most useful as multi-filamentary composites

• Because Nb3Sn is very brittle the wires must be processed to small

final diameters while the Nb and Sn elements are separate

• The Nb3Sn compound is formed by a high temperature reaction

treatment typically at 650°C for as long as 100 hours.

• Typically the coil is wound from the unreacted wire while it is still

ductile, then the entire coil undergoes reaction

• Of course the insulation must remain intact during this process

• NbTi is used for the outer coils up to a field strength of ~9T

To get above 24T we need HTS materials

• Bi2223: (Bi,Pb)2Sr2Ca2Cu3O10-x A Tape – powder-in-tube method; Tc = 110K

- high quality magnets have been made

- while a high critical current density, it is highly anisotropic

To get above 24T we need HTS materials

• Bi2212: Bi2Sr2CaCu2O8-x A Wire, Tc = 90K

- high critical current density and low anisotropy

- has to be processed at a very high temperature just below the melting

temperature of silver

• YBCO: YBa2Cu3O7-d A Tape, Tc = 92K

- uses a substrate known as Hastelloy or a Ni-W alloy providing a high

tensile strength

- Strong anisotropy leads to problems at the ends of coils for NMR

magnets, which are very long to generate a homogenous field

Insulation Cross Sections

434‐NT‐S57‐B 435‐NT‐S57‐B

6

• Coating still shows eccentricity; however, minimum thickness is now about 15 µm, which is within our acceptable range

• Compression test‐coil has been made and is currently in the Mellen furnace for standard heat treatment

• Coating of a 430 m length of Al stand‐in wire starts today to verify reproducibility over long length; if success, coating of 120 m for quad‐layer coil

Coating thicknesses sampled from about 30 cm of conductor

H. Kandel, J. Lu

To get above 24T we need HTS materials

• YBCO: YBa2Cu3O7-d A Tape, Tc = 92K

- uses a substrate known as Hastelloy or a Ni-W alloy (in figure it is labeled

“substrate”) providing a high tensile strength

- Strong anisotropy leads to problems at the ends of coils for NMR

magnets, which are very long to generate a homogenous field

We have been spoiled by NbTi and Nb3Sn Conductors

• The first and maybe for a log time the performance will not just our our

current LTS magnets

- Essentially zero drift

- for solid state NMR – essentially perfect homogeneity

• Shimming an HTS magnet maybe challenging

- for LTS magnets the low order gradients are corrected by coils on

the outside of the main magnetic field coils

- for HTS coils the screening of the currents in such coils makes them

ineffective

- will have to use ferro shims on the inside of the bore

- if an HTS tape is used the shims maybe be different each time the

magnet is energized …. Reshimming with ferroshims??

• Stability – a report on a YBCO coil stated that the half-life of the drift when

the magnet was energized was ~600 days….

- tricks and new techniques are being developed

We have been spoiled by NbTi and Nb3Sn Conductors

• Joints – unless superconducting electrical joints can be made the magnet

will have to be attached to a power supply

- really excellent power supplies have stability of ~1 ppm

- however long ago at Carnegie Mellon the first 600 MHz instrument

was installed (~1980?) – it was not a persistent magnet – yet

linewidths of a ppb were obtained, since only a small amount of

power was needed to maintain the field

- rumors of Bi2212 joints exist

- Bruker claims they have joints for the YBCO that are “better than

they expected” they will be using in their 28T magnets.

• The bottom line is that we should be prepared, at least for the near future to

have high field magnets with somewhat reduced performance in some of

these areas

NMR/MRI Applications as a Function

of Bo Homogeneity & Stability

Bo Homogeneity & Stability

SuperconductingMagnets

High-Res ResistiveMagnets

Series ConnectedHybrid Magnet

Std-Res ResistiveMagnets

25T Keck Resistive Magnet • built in 1996

• 52mm bore size

• 39kA(24MW)

• 20ppm/oC

Field maps before and

after ferromagnetic

shim

NMR signal with

4mm magic-angle

spinning

Bird, Gan, IEEE Appl Supercon, 12 (2002) 447-451

Gan, Kwak, Bird, Cross, Gor'kov, Brey, J Magn Reson, 191 (2008) 135.

Worse case senario

Compensating field fluctuations

~25ppb

Field fluctuations can be corrected if a reference signal (D2O solvent) is acquired

simultaneously and used for correcting the fluctuation to the 1H signal phase.

HO-CH2-CH3

First (& last) Attempt at 45T Hybrid

Z. Gan, P. Gor’kov, T. Cross, A. Samoson, D. Massiot J Am Chem

Soc, 124(2002) 5634-5635

9Al2O3 + 2B2O3 19.6T

40T

High Field Impacts for Quadrupolar NMR: Resolution and Sensitivity

• Boltzman factor B0

• Frequency B0

• Line narrowing B0

• Resolved spinning sideband

• ~20 gain in sensitivity from 9.4 to 19.6T (~400 in time)

2 hrs at 19.6T

(NHMFL)

7 days at 9.4T

(Grandinetti, Ohio State)

17O NMR

27Al NMR

(6-17O) Methyl a-D-Glucopyranoside

Gan et al JACS (2002)

Ultra-High Magnetic Resonances:

Opportunities for

Novel Science

Advantages of High Magnetic Fields coupled with High Homogeneity and High Magnet Stability

•Enhanced Sensitivity for Magn. Reson., e.g. can be greater than Bo4 for quadrupole nuclei

•Enhanced Resolution for Magn. Reson., e.g. enhancements can increase with

dimensionality of the spectra

•New Physical Phenomena at High Field, e.g. new phases

•Altered Physical Phenomena at High Field, e.g. altered relaxation times in

Magn. Reson.

•Different frequency regimes for Magn. Reson., e.g. important for characterizing

dynamics

•Changed Relative Magnitudes of Spin Interactions for Magn. Reson., e.g.

leads to substantial resolution enhancements, such as TROSY

•Increased Magnetic Susceptibility, e.g. enhanced Functional Magn. Reson.

Imaging, e.g. improved alignment of diamagnetic, paramagnetic molecules

•and more….

New resonances appear in these 2D 13C-13C correlations: “Peaks out of Blobs”

Solid-state 2D NMR Correlation Spectra are Significantly Enhanced At High Fields – MORE THAN ANTICIPATED

Renault et al., Angew. Chem. 2010 – Chimeric KcsA-Kv1.3 in Lipid Bilayers

900 MHz500 MHz 750 MHz

Sperling et al., J. Biomol. NMR 2010 – GB1

X,Y 1H

In Combination with State-of

the-Art Probes

HIV-1 Viral Capsid CA ProteinPolenova et al., (2013) J. Am. Chem. Soc.

Proton-Detected

Experiments Stand to

Gain a LOT at

Ultrahigh Fields

1H-13C Correlation Spectrum of an SH3 Domain Reif et al., (2013 Acc. Chem. Res. 46:2089-2097

• Ultrahigh field NMR can provide critical new insight into the composition of biological metabolomes in health and disease.

• A powerful new tool in the drug discovery pipeline

• New combinations with Mass Spec / Chromatographic methods for sorting complex biological mixtures

Spectral Dispersion and Sensitivity for

Natural Products, Metabolomics, etc.

1.5 mm HTS Probe for metabolomics natural products

Mega-Proteins: Structure, Dynamics & Function from UHF NMR

• Elucidating function in the using methyl TROSY:conformational states (A, B, C) have been identified and the interconversion rates characterized.

• Doubling the field strength will lead to unique opportunities for making what is a heroic effort today, routine

• New opportunities such as Ca –TROSY will also arise

• 15N detection – not such a big penaltyRosenweig & Kay, Ann. Rev. Biochem. 2014

Intrinsically Disordered Proteins:

News & Views by Chouard re: Ferreon et al., (2013) Nature

• The ultimate demand for spectral resolution in the hunt for residual structure

15N

–1H

Dip

ola

r C

ou

plin

g (k

Hz)

15N Anisotropic Chemical shift (ppm)

N- Terminus

Interhelical Loop

OS NMR of CrgA: A Membrane Protein IDR

Residual Anisotropy

Nascent Structure

AA DC ACSSer4 0.0 110Val6 0.0 125Asn10 1.0 115Phe12 0.0 120Thr13 0.0 105Val14 0.0 125Ser15 1.0 110Ala16 0.0 130Val17 0.0 125Ser18 1.0 110Arg19 5.2 70Thr20 5.6 75Met22 3.9 105Val24 5.4 70Val26 4.3 75Gly27 5.1 70Ser29 4.0 175

Ser30 8.5 225

AA DC ACSSer53 6.6 178Ala54 4.2 173Ala55 3.6 166Ile56 5.8 78Gly57 5.2 80Ser58 5.0 80Ala60 1.3 125Pro61Thr62 5.5 62Ala63 4.3 78Leu64 5.5 65Asn65 5.0 80Trp66 5.0 85Met67 5.4 88Ala68 1.7 133Leu70 0.0 105

Gly71 0.0 110

9 Ala Sites Labeled

1 Phe Labeled in the IDR

CrgA, the protein that recruits 5 other proteins to the M. tuberculosis divisome.

In Situ (E. coli Membranes) vs.

Isolated, Purified, Reconstituted (in Synthetic Bilayers):

Full length M2 proteinMiao et al.,(2012) Angew Chemie.

In Cell studies are unique and wonderfully well adapted

for NMR – but only at ultrahigh fields

Superoxide dismutase 1 maturation in live human cells: Zn binding,

homodimer formation, chaperone intervention, disulfide bond formation –

all observable at 15 µM, at 950 MHz (Banci et al, Nat. Chem. Bio 2013)

Sharma et al., (2010)Science 330:509-512

900 MHz

So do oriented sample BioNMR Experiments

• M2 Protein (22-62) from

Influenza A

• Structure determined in

uniformly aligned

liquid-crystalline lipid

bilayers

• Enhanced Alignment at

high Fileds

A unique resource that only opens at Ultrahigh Fields: Quadrupolar NMR

Single site 17O labeled gramicidin A in lipid bilayers –samples uniformly aligned & spectra obtained at 19.6 T (Hu et al., J. Am. Chem. Soc. 2005

Dramatical increase in sensitivity and resolution for NMR quadrupolar nuclei partaking of crucial chemical and

biochemical events: Structure, Catalysis, Energy

27Al MAS spectra of A9B2

compound(Gan et al., J. Am. Chem. Soc.2002).

Again – Understanding & Explaining

Biological Function – it’s what NIH wants….

Oriented Sample 17O Gramicidin A -solvation of monovalent cations by this cation channel.

- Goal is narrow linewidths and enhanced sensitivity

- 1 ppm homogeneity and stability will be OK

- The temperature dependence is very interesting and unexplained

- 21T: 17O – 112 MHz

- 36T: 17O – 208 MHz

In Vivo Chlorine and Sodium MRI Imaging of the

Rat Brain at 21.1 T

V. D. Schepkin, M. Elumalai,Kitchen, J.A., C. Qian, P.L.Gor’kov, & W.W. Brey (2013)MAGMA

•35Cl – 20x less sensitive than 23Na

•Biexponential Free Induction Decay

• Loss of 35Cl signal –large quadurpolarinteraction

• High [Cl-] in Rat Glioma correlates tumor progression

Sliding Ring Coil for Neuroimaging in

Verical Bore Magnets – 21.1T

2

3

14

(c)

1 cm

• 33 mm id coil(a) In vivo rat brain(b) Multiple ex vivo mouse brains(c) Human brain section

Alzheimer’s patient• diverse coil loading

(a)

(b)

C. Qian, I.S. Masad, J.T. Rosenberg, M. Elumalai, W.W. Brey, S.C. Grant,P.L. Gor’kov, (2012) J. Magn. Reson. 221: 110-116.

Relaxation Enhanced Ultrahigh Field 1H Magnetic Resonance

Spectroscopy:

Novel spectral fingerprints for stroke in the spectral region downfield of water which contains numerous crucial resonances, but whose direct observation in disease has not been achieved insofar.

Combining highly selective spectral excitation In vivo with 21 T detection generates SNR ratios of >50:1 in <6 sec with virtually complete suppression of water

N Shemesh, JT Rosenberg, JA Muniz, SC Grant, L Frydman, Relaxation Enhanced in-vivo

Magnetic Resonance Spectroscopy at Ultrahigh Fields, in Nature Commun.

Progress towards HTS Magnets

500 MHz Lysozyme Spectra

Maeda et al (2010) IEEE 20:714-717

LTS Magnet LTS/HTS Driven Magnet

Using a Bi2223 coil

• A driven magnet

1.02 GHz HTS/LTS

Magnet

3.6 T of Bi222320.4 T of the outer LTS

coils of the former 920 MHz Magnet

24 T in total – a powered magnet system that achieves good stability and lineshape

mmHashi et al., JMR 2015

1.3 GHz HTS/LTS Magnet Design

mm Iwasa et al., IEEE Trans Appl Supercond, 2015

500 MHz LTS800 MHz HTS (GdBCO – a tape conductor)

• Note the small size of the HTS coil- High current carrying capability

• The GdBCO tape will be would as a pancake not as a coil

• Shaking Coil – novel concept for damping the long term drift

• Note the need for low order shims in the interior of the magnet –most LTS magnets have these on the outside – but this will not be possible with HTS coils.

• Iwasa’s efforts for NMR have been supported by NIH for many years

NHMFL’s NIH-supported pilot project for a 24 T, ≈1ppm, ≈100 µL

magnet

S-2S-3

S-4

T-1

T-2

33

6.0

5 m

m

B

HTS-NMR Prototype≥23.5 T: 17.5 T LTS + 6.3 T HTS

• Utilizing a the outer coils of a high field Oxford Magnet (17.5 T)

• For the HTS conductor a Bi2212 wire conductor – the only HTS wire conductor available.

• Wire conductor’s have the advantage that the current is constrained to a nearly linear path and they can be wound in a coil.- this leads to a much more stable magnet- it also leads to a more homogeneous and reproducible field.

“Platypus”

NHMFL’s 30T “mammal”: Proposals (D. Markiewicz & H. Weijers)

HTS section shares many design parameters with 32 T design

Field homogeneity and stability are the major new challenges

Bio-NMR

Science and Technology at

High Fields: 36 T Series

Connected Hybrid Magnet for NMR

& MRI

Bruker AVANCE III HDTM High Performance Ultra High Frequency Digital NMR Console

• A Collaboration with Bruker on Field Regulation and Stabilization; 17O NMR spectroscopy

• Three 1H Frequencies between 23 and 36 T for frequency dependence studies.

• Triple Resonance• Gradients for micro imaging an option

• Unique series connection for the 12T superconducting outer magnet with the 24 T resistive insert designed for enhanced homogeneity

A Prelude to HTS Magnets with fields of 30, 40, 50??T

Scientific Plan

VISION: A Interdisciplinary Program that takes Unique Advantage of the:

• Enhanced Homogeneity

• Increased Run-Time compared to the Resistive Magnets• High Field Strength

• Improved Temporal Stability• Enhanced Experimental Flexibility

PROBES:

• Low g MAS Probe

• 2.0 mm CP MAS HCN Probe• Static 1H-X Probe

• 1.6 mm CP MAS Probe• Micro-Imaging Probe

Probes set up with Internal & External Locks

SCH SPECIFICATIONS

• 1 ppm temporal stability • 1 ppm homogeneity

• 15 hour run time • 14 MWatts

• 40 mm bore

The Superconducting Outsert is

Complete, Tested and in its Cryostat

Version #1 of this Magnet is now operational at 36 Tesla in Berlin (not for NMR).

An Exciting and Very Challenging

Future for Solid State NMR

lies ahead with

HTS Magnets