Ultra-High Field Nuclear Magnetic Resonance (NMR) Spectroscopy: Applications at 1 GHz and Beyond

Nuclear magnetic resonance (NMR) spectroscopy is a powerful non-invasive analytical technique with wide applications that can observe multiple nuclear species at a site-resolved level. Despite this, NMR has inherent low sensitivity compared to other analytical techniques. A principal approach to improve the sensitivity and resolution of the NMR experiment is to increase the strength of the external static magnetic field (B₀), for which the upper practicable limit has gradually increased over five decades. The relatively recent use of high-temperature superconducting materials, such as Bi₂Sr₂Ca₂Cu₃O_x (Bi-2223), Bi₂Sr₂CaCu₂O_x (Bi-2212) or REBa₂Cu₃O_7-x (REBCO, RE = rare earth), has enabled construction of ultra-high field NMR magnets. Over twenty commercial ultra-high field NMR instruments at 1.0, 1.1 and 1.2 GHz (23.5, 25.9 and 28.2 Tesla, respectively) have been installed worldwide in the past several years, with more to come. NMR at ultra-high fields benefits both solution-state and solid-state NMR applications. The potential improvements in sensitivity and resolution in NMR spectra are particularly important for studying the structure, dynamics and ligand interactions of biomolecules, which can suffer from poor sensitivity and prohibitive signal crowding. The benefits of using ultra-high field NMR have begun to be demonstrated on various sample types, including intrinsically disordered proteins, membrane proteins, amyloid fibrils, viral capsids, bacterial chlorosomes, fungal cell walls, and whole human cells. Alongside optimisations in sample preparation, probe design and pulse sequences, and exploitation of dynamic nuclear polarisation (DNP), ultra-high field magnets are contributing to an exciting period for improving the sensitivity and resolution of NMR spectra in the study of more complex biomolecules and other samples.