GHz Class NMR

The strength of the magnetic field is one of the most important properties of an NMR spectrometer. The dispersion (i.e. the “distance” of two peaks in an NMR spectrum) is enhanced at higher magnetic fields. For the investigation of substances with a large number of peaks, higher magnetic fields render it possible to separate different peaks from one another, making GHz-class NMR an invaluable tool for structure determination. An example is shown in Figure 1.  

Another great advantage of higher magnetic fields is the improved sensitivity that can be achieved in an NMR experiment. Higher magnetic fields lead to a larger number of nuclear spins of the sample residing in the lower energy quantum state, which results in a stronger NMR signal. This is particularly beneficial for multi-dimensional NMR experiments, where the sensitivity increases additionally with the power of the number of dimensions.

For many years, high-resolution NMR was limited to a magnetic field of 23.5 Tesla, equivalent to a proton resonance frequency of 1.0 GHz. This limit was set by the physical properties of metallic, low-temperature superconductors (LTS), and it was first reached in 2009 with an Avance 1000 spectrometer at the Ultra-High Field NMR Center in Lyon, France.

High-temperature superconductors (HTS), first discovered in the 1980s, opened the door towards even higher magnetic fields at low temperatures, but considerable challenges in YBCO HTS tape manufacturing and in superconducting magnet technology made further UHF progress daunting until the early 2020ies.

Bruker's 1.0 GHz Ascend Evo, and 1.1 and 1.2 GHz Ascend magnets utilize a sophisticated hybrid design with high-temperature superconductor (HTS) in the inner sections and low-temperature superconductors (LTS) in the outer sections of the magnet, as illustrated in Figure 2. Bruker’s GHz-class NMR magnets feature a 54 mm room-temperature bore (“standard bore”) and have exquisite homogeneity and field stability compatible with the demanding requirements of high-resolution NMR.

The enhanced resolution and sensitivity make GHz-class NMR the ideal tool for many areas of research, in particular for material science and structural biology. The most important benefits are the following:

• Reduced sample quantity needed: Due to the enhanced sensitivity, UHF NMR typically requires only small amounts of sample, which is particularly advantageous for rare and limited samples.
• Atomic-level resolution: GHz-class NMR provides atomic-level resolution on an unprecedented level. For biological samples, this is particularly pronounced for small and medium-sized proteins.
• Solution-state information: GHz-class NMR can work in solution, offering insights into the behavior of biomolecules in conditions closer to their native environment, which is essential for understanding their biological functions.
• Analysis of dynamic structures: GHz-class NMR spectroscopy is excellent for studying the dynamics and motions of biomolecules in solution, providing insights into conformational changes, flexibility, and interactions. This capability to study dynamics is particularly beneficial in understanding protein folding, function, and interactions.
• Ability to study ligand interactions: UHF NMR is well-suited for studying interactions between proteins and small molecules, enabling detailed analysis of binding sites and dynamics, crucial for drug discovery and design.

Bruker’s GHz-class spectrometers are available with a large selection of NMR probes, including CryoProbes for solution-state NMR and fast-spinning MAS solid-state NMR probes. The most popular probes for Bruker’s GHz-class NMR spectrometers are the following:

• TCI (“inverse”) triple-resonance CryoProbes with dedicated channels and cold preamplifiers for H, C and N. These TCI solution-state probes are optimized for proton detection. They are equipped with a deuterium lock channel and a gradient coil.
• TXO (“observe”) triple-resonance CryoProbes with dedicated channels and cold preamplifiers for H, C and N. The TXO probes are optimized for X-detection (i.e. N and C). They are equipped with a deuterium lock channel and a gradient coil.
• TXI triple-resonance room-temperature probes feature dedicated channels for H, C and N, as well as a deuterium lock channel and a gradient coil.
• BBI dual-resonance room-temperature probes have a proton channel, a broadband channel, a deuterium lock channel, and a gradient coil. They make solution-state GHz-class spectrometers particularly versatile, as the broadband channel expands the range of accessible nuclei considerably.
• The advantages of GHz-class spectrometers are particularly pronounced in solid-state NMR. Bruker offers an extensive range of CPMAS probes. For GHz-class spectrometers, probes with the fastest spinning speeds (i.e. probes for 0.4 mm, 0.7 mm, 1.3 mm and 1.9 mm rotors) are typically employed. The most common probes are triple-resonance probes (HCN), as well as probes primarily dedicated to material science (HX).
• Bruker's well-known magnetic resonance (MR) microscopy probes are also available for GHz-class spectrometers. MR microscopy is used to image small samples. With GHz-class spectrometers, highest spatial resolutions or spatially localized chemical information can be achieved.

NMR research has entered a new era with the introduction of GHz-class spectrometers, which enable unprecedented resolution and sensitivity for studying complex biological systems and materials. Europe has been at the forefront of this innovation, with several 1.2 GHz NMRs already in operation across the continent. The US and Asia-Pacific are also embracing this technology, with the first 1.2 GHz NMR in the US and the first 4.2 K single-story 1.0 GHz NMR in Japan. More GHz-class NMRs are being installed or planned in these regions, reflecting the growing demand and recognition for this powerful and versatile tool for scientific discovery.
Below, you can find more information about some of the leading research institutions that have chosen GHz-class NMR for their projects.

In 2019, Bruker successfully installed the world's first 1.1 GHz NMR system at St. Jude's Children Research Hospital in Memphis, Tennessee.

Dr. Charalampos Kalodimos, Chair of the Structural Biology Department at St. Jude's Children Research Hospital stated: "We are thrilled to have received the first 1.1 GHz NMR spectrometer, which will be our most important tool to perform research in the area of dynamic molecular machines such as molecular chaperones and protein kinases. We commend Bruker on this impressive technological achievement."

Shortly after, in early 2020, Bruker installed the world's first 1.2 GHz NMR system at the CERM of the University of Florence. CERM is an Italian center of the European research infrastructure in structural biology.

Following the successful installation, professors Lucia Banci and Claudio Luchinat at the CERM of University of Florence, stated: “We are thrilled to have the world’s first 1.2 GHz NMR spectrometer successfully installed in our lab. We are looking forward to putting the instrument to use in our research on the structures and function of proteins linked to neurodegenerative diseases, such as Alzheimer's and Parkinson's Diseases, as well as in cancer and viral protein structure and functional research. Right now, we are actively working on SARS-CoV-2 proteins, and we will soon record the first 1.2 GHz NMR spectra of a protein from this coronavirus!”

Later in 2020, Bruker successfully installed the world’s second 1.2 GHz NMR spectrometer at Eidgenössische Technische Hochschule (ETH) Zürich in Switzerland. This 1.2 GHz spectrometer is the first one that is configured for solid-state NMR.

At the time, Professors Beat Meier, Matthias Ernst and Alexander Barnes at ETH stated: "We are very excited to have the world's first 1.2 GHz solid-state NMR spectrometer successfully installed in our lab. The system was delivered just a couple of months ago and the installation and energizing of the NMR magnet went exceptionally well. The completion of the installation marks the culmination of a project that we started with Bruker almost a decade ago. We are very much looking forward to starting our first ultra-high field solid-state NMR experiments.“

ETH utilize their 1.2 GHz NMR system to enable the development of new solid-state NMR techniques, and to apply these techniques to study materials and biological systems, including proteins fibrils which are linked to diseases such as Parkinson's and Alzheimer's. The 1.2 GHz spectrometer will also be used as a basis for further improving NMR methodology towards in-cell structural biology, and to investigate solid catalysts and functional materials, e. g. for energy conversion and data storage.

At the beginning of 2021, Bruker was proud to announce the successful installation of its fourth 1.2 GHz NMR system at the Max Planck Institute (MPI) for Biophysical Chemistry in Göttingen, enabling their research teams to deliver new insights into the SARS-CoV-2 nucleocapsid (N) protein, and aiding the deeper molecular understanding of Parkinson’s and Alzheimer’s diseases.

Professor Christian Griesinger, Director and Scientific Member at the Max Planck Institute for Biophysical Chemistry in Goettingen, commented: “The new 1.2 GHz spectrometer will allow us to characterize droplets and oligomers of IDPs that are key markers in diseases such as COVID-19, neurodegenerative diseases and cancer, and which cannot be studied using crystallography or cryo-EM.”

Dr. Markus Zweckstetter, Professor at the University of Goettingen and Group Leader at the German Center for Neurodegenerative Diseases, added: “Our first experiments after the installation of the new ultra-high field NMR system have focused on the SARS-CoV-2 nucleocapsid N-protein that is of key relevance for viral-host interactions and viral replication biology. The liquid-like properties of viral replication machineries in combination with the many intrinsically disordered regions of the N-protein make this research ideally suited for GHz-class NMR.”

Delve into the exciting world of GHz-class NMR technology through our exclusive interviews with leading scientists and researchers. Our video series showcases how this cutting-edge technology is pushing the boundaries of functional structural biology, enabling unprecedented resolution in the study of proteins and protein complexes. Hear firsthand how high-field GHz-class magnets are being leveraged to tackle key questions in structural biology, offering new dimensions of insight and solutions to some of society’s most pressing challenges. Watch now to stay at the forefront of scientific discovery and see how GHz-class NMR is transforming research and innovation.