Applications


     The Field-Cycling technique in NMR has been applied to various field-dependent studies. Several keywords, NMR dispersion (NMRD), and relaxometry, all point to the field-cycling technique in NMR. The main idea is to measure NMR relaxation on a frequency basis. Its applications include material science, such as polymer dynamics, and structural biologies, such as membrane dynamics and protein dynamics, and relaxivity measurements on contrast agents in the MRI field, etc.

BioMolecular Dynamics

    Within applications of relaxometry, protein applications require the most high resolution and sensitivity. Due to the value range of relaxation parameters of biomolecular systems, in addition to the demand for high resolution, a rapid field switch is essential.
    Recently, high-field static NMR becomes insufficient for biological system studies. Protein dynamics investigation requires field-dependent term in relaxation rate to extract the parameters in molecular motions. To understand the spectra density function of protein dynamics, field-dependent longitudinal relaxation becomes an essential study in many biological systems [A. Refield, Journal of Biomolecular NMR 52(2):159-77]. In addition to fundamental physics studies of protein dynamics, ligand-based 19F-NMR rescreening was reported as an efficient method for performing ligand binding. 19F longitudinal relaxation in the different magnetic fields uses dynamics properties of ligands to carry out fragment-based screening[C. Dalvit and M. Piotto, Magnetic Resonance in Chemistry 55(2) (2016), DOI: 10.1002/mrc.4500]


      The sensitivity and stability of High-Field Field-Cycler (HFFC) have been proofed to apply to protein dynamics investigation in various laboratories. Additionally, the proof of sensitivity has been published in Journal Biomolecular NMR (2016). The system was successfully installed in several commercial spectrometers equipped with different probe systems, including a 5mm cryo-probe system.
      The following 15N-1H HSQC 700 MHz spectrum (a) from R1 measurements of 500 μM 15 N-ubiquitin sample, was acquired in 20 minutes under field cycling from 16.5 T to 1.0 T with the relaxation delay time of 48 ms. The used probehead was a 5 mm TCI Bruker cryoprobe. The resonance enclosed by the dashed square shows the sensitivity enhancement by utilizing a higher field spectrometer and cryo-probe system. (b) 1H slices at 121.3 ppm 15N chemical shift corresponding to the long dashed rectangle area of the previous 2D spectrum are displayed in the lower slice. The red slice is extracted from 1.0 T R1 measurement acquired at 600 MHz, and the black is extracted from the same shuttling experiment at 700 MHz.

Relaxivity on Contrast Agents

      In addition to protein dynamics investigation, relaxivity measurement on contrast agents is also a hot topic in NMR relaxometry studies. Relaxivity measurement is also a field-dependent relaxation measurement but observing on the solvent side. Its important application as contrast agents in MRI. The agents perturb the relaxation mechanism in water to increase the imaging contrast in the region of interest.
      Our field-cycler has been utilized in such studies and opened a comparable magnetic field range of relaxivity measurement as current MRI scanners.


Ref:
  • Scientific Reports 7, Article number: 44770 (2017) doi:10.1038/srep44770
  • In Vivo Field-Cycling Relaxometry Using an Insert Coil for Magnetic Field Offset. Magnetic Resonance in Medicine 72(5) DOI: 10.1002/mrm.25040

Long-lived State Relaxation:

      Our system is also suitable to investigate long-lived state relaxation. The field-cycler can play the role of a sample carrier to carry the sample to the desired magnetic field with controllable speed.

Ref. long-lived state relaxation:
  • M. Carravetta, O.G. Johannessen and M. H. Levitt, "Beyond the T1 limit: Singlet Nuclear Spin States in Low Magnetic Field", Phys. Rev. Letters 92(15), 153003 (2004).
  • M. Carravetta and M. H. Levitt, "Long-lived nuclear spin states in high-field solution NMR", J. Am. Chem. Soc. 126, 6228-6229 (2004).

Material Science:

      Dynamics of polymers have been investigated by NMR field-cycling relaxometry for decades. The field-dependent relaxation (relaxomtry, or so called dispersion NMR, “NMRD”) allows researchers to have a detailed description of the amplitude and characteristic time of molecular motions.

Ref.:
  • M. Hofmann, C. Gainaru, B. Cetinkaya, R. Valiullin, N. Fatkullin, and E. A. Rössler, “Field-Cycling Relaxometry as a Molecular Rheology Technique: Common Analysis of NMR, Shear Modulus and Dielectric Loss Data of Polymers vs Dendrimers“ Macromolecules 2015 48 (20), 7521-7534 DOI: 10.1021/acs.macromol.5b01805
  • Siegfried Stapf and and Rainer Kimmich*, “Field-Cycling Nuclear Magnetic Resonance Relaxometry and Field-Gradient Nuclear Magnetic Resonance Diffusometry of Polymers Confined in Porous Glasses:  Evidence for a Restricted-Geometry Effect”, Macromolecules 1996 29 (5), 1638-1641 DOI: 10.1021/ma9502112