Applications


      Field-cycling technique in NMR has been applied on various field dependent studies. Several key words, NMR dispersion (NMRD), and relaxometry, all point to the field-cycling technique in NMR. The main idea is to measure the relaxation in the frequency basis. Its applications include material science, such as polymer dynamics, and structural biology, such as membrane dynamics and protein dynamics, and relaxivity measurements on contrast agent in MRI field, and 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 of high resolution, rapid field switch is essential.
      Recently, high-field static NMR become insufficient for biological system studies. Protein dynamics investigation requires field-depedent 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 essential study in many biological systems [A. Refield, Journal of Biomolecular NMR 52(2):159-77]. In addtiion to fundamental physics studies of protein dynamics , ligand-base 19F-NMR recreening was reported as an efficient method for performing ligand binding. 19F longitudinal relaxation in different magnetic field 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) has been proofed to apply on protein dynamics investigation in various laboratories. Additionally, the proof od sensitivity has been published in Journal Biomolecular NMR (2016). The system was successfully installed in several commercial spectrometers equipped with different probe systems, including 5mm cyro-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 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 solvent side. Its important application is contrast agents in MRI. The agents perturb the relaxation mechanism in water in order to increase the imaging contrast at 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 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 behavior of polymers has 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