Mini‐Birdcage Coil for Portable Nuclear Magnetic Resonance Spectroscopy: Design, Simulation, and Performance Analysis

Nuclear magnetic resonance (NMR) spectroscopy is a valuable and complementary tool in environmental research, but it is underutilized due to the cost, size, and maintenance requirements of standard "high-field" NMR spectrometers. "Low-field" NMR spectrometers are a financially and physically accessible alternative, but their lower sensitivity and increased spectral overlap limit the analysis of heterogeneous environmental/biological media, especially with fast-relaxing samples that produce broad, low-intensity spectra. This study therefore investigates the potential of the steady-state free precession (SSFP) experiment to enhance signal-to-noise ratios (SNRs) of fast-relaxing, complex samples at both high- and low-field. SSFP works by obtaining steady-state transverse signal using a train of equally spaced radiofrequency pulses with the same flip angle and a time between pulses less than the transverse relaxation time, allowing for thousands of scans to be summed in a short time period. Here, 13C-SSFP is applied to samples of varying complexity (egg white, dissolved organic matter, and crude oil) at low-field and at high-field for testing and comparison. The potential of in vivo SSFP NMR is additionally investigated by applying 31P-SSFP to live Eisenia fetida at high-field. In some samples, SSFP increased 13C SNR by over 2000% at both high-field and low-field compared to standard 13C NMR and enabled detection of peaks that were not observable by standard 13C NMR. Ultimately, SSFP holds great potential for improving analysis of fast-relaxing, complex samples, which could in turn make low-field NMR spectroscopy a more effective tool not only in environmental/biological research but also in numerous other disciplines.

Nuclear magnetic resonance (NMR) spectroscopy is a wide-spread analytical technique which is used in a large range of different fields, such as quality control, food analysis, material science and structural biology. In the widest sense, NMR is an analytical technique to determine the structure of molecules. At the time of writing this manuscript, commercial NMR spectrometers with a proton resonance frequency ⩾900 MHz are only available from Bruker. In 2019, Bruker installed the first 1.1 GHz (25.8 T) NMR spectrometer at the St. Jude Children Research Hospital in Memphis, Tennessee, followed by the installation of the first 1.2 GHz (28.2 T) NMR spectrometer at the University of Florence in Italy in 2020. These were the first commercial NMR spectrometers operating at magnetic fields in excess of what can be achieved with conventional low temperature superconductors, and which depend on high temperature superconductors to generate the required magnetic field. In this paper, the requirements on commercial NMR magnets are discussed and the history of high-field NMR magnets is reviewed. Bruker’s R&D program for 1.1 and 1.2 GHz NMR magnets and spectrometers will be described, and some of the key properties of these first commercial NMR magnets with high-temperature superconductors are reported.

The accurate characterization of relative composition in multicomponent polymer systems such as statistical copolymers, block copolymers, and polymer blends is critical to understanding and predicting their behavior. Typically, polymer compositional analysis is performed using 1H Nuclear Magnetic Resonance (NMR) Spectroscopy which provides quantitative chemical group concentrations without prior calibration. This utility has led 1H NMR spectroscopy to become a routine method for the molecular characterization of polymers. Unfortunately, due to cost constraints, NMR spectroscopy is rarely used for routine materials verification such as quality control in industrial settings that commonly lack on-site advanced instrumentation facilities. Recently, low-field or so-called benchtop NMR spectrometers have been introduced commercially as a less expensive alternative to higher field, and costlier, NMR spectrometers. Here, we examine the capability of a low-field 1H NMR spectrometer (60 MHz) for the compositional analysis of select block copolymers and polymer blends by direct comparison with results obtained using a 400 MHz NMR spectrometer. In the analysis of high 1,4-content polyisoprene we find quantitative agreement between the 400 and 60 MHz spectrometers. Furthermore, quantitative agreement is demonstrated for compositional analysis of commercially available poly(styrene-b-isoprene-b-styrene) (SIS) and poly(styrene-b-butadiene-b-styrene) (SBS) triblock copolymers and polymer blends of polystyrene/polyisoprene (PS/PI) and polystyrene/poly(methyl methacrylate) (PS/PMMA) that also serve as proxies for statistical and block copolymer analysis. Overall, we find low-field 1H NMR spectroscopy to be an accessible, powerful and useful tool for polymer characterization.

NMR in Environmental Science

Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful analytical tool that has significantly advanced the understanding of cattle metabolism. Nuclear Magnetic Resonance (NMR) spectroscopy plays a pivotal role in the study of cattle metabolism, offering distinct advantages over other spectrometric methods. NMR spectroscopy is a powerful analytical tool that provides detailed molecular insights by exploiting the magnetic properties of atomic nuclei. Unlike mass spectrometry and infrared spectroscopy, NMR does not require extensive sample preparation or destruction, preserving the integrity of biological samples. This non-invasive nature is particularly beneficial for longitudinal studies in cattle, where metabolic changes over time are of interest. One of the key strengths of NMR spectroscopy is its ability to simultaneously detect and quantify a broad range of metabolites in complex biological matrices, such as blood, urine, and tissue extracts. This comprehensive metabolic profiling is crucial for understanding the biochemical pathways and physiological states in cattle. NMR's high reproducibility and quantitative accuracy further enhance its suitability for metabolic studies, enabling precise monitoring of metabolic fluctuations in response to dietary changes, environmental stressors, or disease conditions. NMR spectroscopy also offers unique advantages in elucidating structural information about metabolites. Through multidimensional NMR techniques, researchers can determine the molecular structure and conformation of metabolites, providing deeper insights into metabolic functions and interactions. This structural elucidation is often challenging with other spectrometric methods, which may lack the resolution or require derivatization of samples. Moreover, NMR spectroscopy's non-destructive nature allows for the analysis of living tissues and in vivo studies, facilitating real-time monitoring of metabolic processes. This capability is instrumental in studying dynamic metabolic responses and adaptations in cattle under different physiological states. Additionally, the development of advanced NMR techniques, such as high-resolution magic angle spinning (HR-MAS) and hyperpolarization, has further expanded the scope of NMR applications in metabolic research. NMR spectroscopy stands out as a superior method for studying cattle metabolism due to its non-destructive approach, comprehensive metabolic profiling, structural elucidation capabilities, and potential for in vivo analysis. These advantages make NMR an indispensable tool in advancing our understanding of cattle metabolism and improving livestock health and productivity. Keywords: Nuclear Magnetic Resonance (NMR), Cattles, Metabolomics.

The development of effective remedial technologies for the destruction of environmental pollutants requires the ability to clearly monitor degradation processes. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for understanding reaction progress; however, practical considerations often restrict the application of NMR spectroscopy as a tool to better understand the degradation of environmental pollutants. Chief among these restrictions is the limited access smaller environmental research labs and remediation companies have to suitable NMR facilities. Benchtop NMR spectroscopy is a low-cost and user-friendly approach to acquire much of the same information as conventional nuclear magnetic resonance (NMR) spectroscopy, albeit with reduced sensitivity and resolution. This paper explores the practical application of benchtop NMR spectroscopy to understand the degradation of perfluorooctanoic acid using sodium persulfate, a common reagent for the destruction of groundwater contaminants. It is found that Benchtop 19 F NMR spectroscopy is able to monitor the complete degradation of perfluorooctanoic acid into fluoride; however, the observation of intermediate degradation products formed, which can be observed using a conventional NMR spectrometer, cannot be readily distinguished from the parent compound when measurements are performed using the benchtop instrument. Under certain reaction conditions, the formation of fluorinated structures that are resistant to further degradation is readily observed. Overall, it is shown that benchtop 19 F NMR spectroscopy has potential as a quick and reliable tool to assist in the development of remedial technologies for the degradation of fluorinated contaminants.

A nuclear magnetic resonance advance. Imaging fluorinated anesthetics in the brain.

Low-cost, high-accuracy characterization of polymeric materials is critical for satisfying societal demand for high-quality materials with ultra-specific requirements. Low-field nuclear magnetic resonance (NMR) spectroscopy presents an opportunity to replace costlier or destructive methods while utilizing nondeuterated solvents. Many factors play key roles in the ability of low-field NMR spectroscopy to accurately analyze polymer systems. Sample characteristics such as polymer concentration, composition, and molecular weight all directly affect the capability of low-field spectrometers to accurately determine polymer microstructure compositions. In addition to inherent sample properties affecting instrumental accuracy, many choices concerning instrumental parameters (including number of scans, relaxation delay, spectral width, and points per scan) must be made that impact the quality of the resulting NMR spectra. In this work, we benchmark the capability of a 60-MHz low-field NMR spectrometer for analyzing polymer materials using mixed microstructure polyisoprenes as a model polymer system of interest. The aforementioned critical sample and instrumental variables are varied, and we report on the ability to quantitatively characterize polyisoprene microstructure to within 1-2% of a higher field NMR spectrometer (400 MHz). We anticipate our findings to be generally applicable to other low-field spectrometers of similar field strength and other polymer systems.

Nuclear magnetic resonance (NMR) spectroscopy, also known as magnetic resonance spectroscopy, is a preeminent and noninvasive analytical technique that provides detailed information about the structure, dynamics, reaction state, and chemical environment of molecules. The development of NMR spectroscopy has led to the awarding of many Nobel Prizes, and today NMR spectroscopy serves as an important and irreplaceable tool in physics and chemistry. Two-dimensional (2D) NMR is effective at separating resonances which have similar chemical shifts, although the interpretation of 2D spectra can be challenging. A systematic density operator-based derivation will aid the understanding of the quantitative mechanism of 2D NMR spectroscopy and the interpreting of outcomes of 2D NMR experiments. Therefore, in this study, we systematically analyzed and compared the quantitative basis of 2D and 1D NMR. Meanwhile, as a proof of principle, simulations using the FID Appliance software toolkit were performed and interpreted using a brain phantom, a popular model for studying brain metabolites. The scheme shown in this paper will facilitate the understanding of quantitative 2D NMR spectroscopic analyses in chemistry and biology.

SummaryThe aim of this work was to determine whether the decreased motion of water in agar gels (2.5–12.5% agar) resulted not only from the chemical interaction of the water molecules with the agar macromolecules but also from obstruction by the gel networks. Relaxation experiments were conducted using a 500‐MHz nuclear magnetic resonance (NMR) spectrometer. Diffusion experiments were conducted using a 23‐MHz NMR spectrometer with diffusion times ranging between 15 and 200 ms and a 500‐MHz NMR spectrometer with a fixed diffusion time of 10 ms. This study shows that the interaction of water with hydroxyl groups of agar macromolecules resulted in faster relaxation and slower self‐diffusion of water. The time‐dependent self‐diffusion coefficient of water provides clear evidence of the obstructive effects of the agar gel network on diffusion. This work is the first report on restricted diffusion of water in agar gel systems.

In the situation when both cartilage and its underlying bone are damaged, osteochondral tissue engineering is being developed to provide a solution. In such cases, the ability to non-invasively monitor and differentiate the development of both cartilage and bone tissues is important. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) have been widely used to non-invasively assess tissue-engineered cartilage and tissue-engineered bone. The purpose of this work is to assess differences in MR properties of tissue-engineered bone and tissue-engineered cartilage generated from the same cell-plus-scaffold combination at the early stage of tissue growth. We developed cartilage and bone tissue constructs by seeding human marrow stromal cells (HMSCs, 2 million/ml) in 1:1 collagen/chitosan gel for four weeks. The chondrogenic or osteogenic differentiation of cells was directed with the aid of a culture medium containing chondrogenic or osteogenic growth factors, respectively. The proton and sodium NMR and waterproton T1, T2 and diffusion MRI experiments were performed on these constructs and the control collagen/chitosan gel using a 9.4 T ((1)H freq. = 400 MHz) and a 11.7 T ((1)H freq. = 500 MHz) NMR spectrometers. In all cases, the development of bone and cartilage was found to be clearly distinguishable using NMR and MRI. We conclude that MRS and MRI are powerful tools to assess growing osteochondral tissue regeneration.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique that allows non-invasive studies of biomolecules at atomic resolution. It provides information on structure and dynamics of biomolecules and is also broadly used in small molecule characterisation. This thesis explores new possibilities of NMR spectroscopy to characterise molecular and cellular systems, the!chaperone–protein interactions in the periplasm of E. coli and the metabolism of eukaryotic cells upon external modifications. In the first part of this thesis, basic concepts of NMR spectroscopy are described, as well as the specific NMR experiments used in the experimental part. The second part of the thesis describes the application of NMR spectroscopy to characterise chaperone–protein complexes. Site-specific intermolecular short-range contacts were detected in a membrane–protein–chaperone complex. This was achieved by an orthogonal isotope–labeling scheme that permits the unambiguous detection of intermolecular NOEs between the well–folded Skp chaperone and the unfolded outer membrane protein A substrate ensemble. The residues involved in these contacts are part of the chaperone–substrate interface. Furthermore, the interaction between the periplasmic chaperone SurA and the BamA–POTRA domains was characterised by NMR spectroscopy. This interaction is supposed to induce the delivery of unfolded outer membrane protein substrates to the BAM complex for their insertion into the outer membrane of E. coli. The combination of sequence–specific assignment using triple–resonance experiments and chemical shift mapping upon interaction revealed the mechanism of SurA interaction with POTRA. A destabilization of SurA and the release of a hydrophobic surface on POTRA1 upon interaction presumably lead to the handover of the OMP precursor to the Bam complex. The third part of the thesis describes studies of cellular metabolism by NMR spectroscopy by footprinting method and in living cells. 1D NMR experiments, combined with metabolite quantification methods characterise the metabolic changes in cells infected by S. flexneri and provide new insights into the infection mechanism of this highly virulent bacterium. Furthermore, the potential of dissolution dynamic nuclear polarisation (DNP) NMR spectroscopy in the characterisation of real time metabolic processes in living macrophages was successfully explored showing that dissolution–DNP NMR spectroscopy can be applied to a broad range of cell systems, and can become routinely applied for metabolic studies in the cell.

Nuclear magnetic resonance (NMR) spectroscopy was invented and developed over six decades ago as an integral part of the chemical and structural analysis of small molecules, polymers, biomaterials and hybrids. High-resolution nuclear magnetic resonance (NMR) spectroscopy plays a special role. Nuclear magnetic resonance methods are mainly used for the structural analysis of synthetic and biosynthetic organic and organic compounds and natural products, as well as for the identification of one or more components in complex matrices. Nuclear magnetic resonance spectroscopy is also one of the most powerful analytical tools for the qualitative and quantitative analysis in biological fluids of low-molecular-weight autotrophic metabolites produced by medicines and narcotic drugs. There is a growing trend towards the use of high-resolution NMR spectroscopy in food science. In this context, we will focus on the importance of NMR spectroscopy for studying low-molecular-weight organic materials using selected examples. High-resolution nuclear magnetic resonance (NMR) spectroscopy plays a special role.

The objective of this chapter is to familiarize the reader with nuclear magnetic resonance (NMR) spectroscopy, its basic principles, its utility as an analytical tool for investigating biofluids, and to describe the instrumentation and related hardware necessary to operate a functional NMR-based metabonomics laboratory. Nuclear magnetic resonance spectroscopy is a powerful approach because it combines the provision of detailed molecular information with thepossibility of understanding whole molecule dynamic properties such as diffusion, plus the ability to carry out quantitation. Although powerful in its own right, NMR spectroscopy can be regarded as complementary to other analytical chemical techniques. For example, it can provide information on substances with no UV chromophores such as carbohydrates. It is a universal detector in that if the molecule under study contains NMR-active nuclei these should be detectable, unlike in mass spectrometry where analyte observation can be influenced by selective ionization. Most NMR spectroscopic experiments are carried out in solution for the purpose of identifying the structures of small chemical molecules, including natural products, but there is a wealth of high resolution applications in other areas, such as determining the threedimensional (3D) structures of proteins as well as analyzing complex biological mixtures such as biofluids for metabonomics applications. In addition, there is much effort devoted to solid state NMR spectroscopy where special techniques have to be used to overcome very broad NMR peaks and hence to recover useful chemical information. Finally, NMR spectra can be obtained from living humans and animals and in vivo NMR or magnetic resonance spectroscopy (MRS), as it is known, has found use in disease diagnosis. The same technology and principles lie behind magnetic resonance imaging (MRI), now widely available in hospitals for clinical diagnosis.

Solution–state nuclear magnetic resonance (NMR) spectroscopy is a rich source of information that can be exploited to elicit the three–dimensional structure of proteins, the nature of their interactions with other molecules, as well as biological function and dynamic properties. Even though NMR was established in the field of chemistry by the early 1950s it was not until the early 1980s that the first three–dimensional solution structure of a small protein was determined. From that time on, however, NMR has come to play a major role in the field of structure–function research on proteins and other biological macromolecules. It would indeed be difficult to imagine that some of the latest developments in this field, for instance the rapid establishment of many larger proteins as mosaic multi–domain assemblies of independent folding units or our recent understanding of protein folding pathways, without the insights provided by NMR spectroscopy. Despite the substantial impact already contributed by the application of NMR to solve biological problems, it is perhaps still arguable that only a fraction of the experimental parameters that can be derived from NMR spectroscopic examination of proteins have so far been fully exploited. In the last decade, NMR spectroscopy has been boosted by enormous technical improvements, which strive to bypass the classical bottlenecks of structure–function studies of proteins. As a result of these new developments, a greater number of experimental NMR parameters can now be interpreted in a meaningful way, while others have recently become accessible for the first time. The turn of the century therefore appeared poised to witness a new spurt in both the development of new NMR techniques and the expansion of their routine application in protein research. The problems that have been plaguing protein NMR spectroscopists for many years – the bewildering complexity of overcrowded spectra, which can be impossible to analyse, fast nuclear relaxation in large molecules (molecular weight greater than 20 000) leading to low sensitivity, the relative paucity of experimental constraints in the calculation of three–dimensional molecular structures, for example – appear to have been overcome within a few years by the cooperative effect of technological and methodological innovations. These developments include the extension of isotope labelling from 15 N to 13 C and 2 H, the introduction of highly stable superconducting magnets with ever–increasing homogeneous magnetic–field strengths of 20 T (corresponding to a proton NMR frequency of 800 MHz) and higher, and the exploitation of the experimental consequences of newly rediscovered physical phenomena, such as the partial alignment in solution of proteins in strong magnetic fields or liquid crystals, and the interference effects of different mechanisms contributing to nuclear relaxation. It is therefore anticipated that the current pace in the development of NMR spectroscopy into a yet more powerful tool will speed up in the new millennium rather than slow down. In this paper, we will describe the basic principles behind the most important of the recent developments in protein NMR spectroscopy, which include aspects of spectrometer hardware and software, NMR experiments, isotope labelling and data analysis. These facets will then be discussed in terms of sample applications to illustrate their use as practical tools in addressing biological and biophysical phenomena at the molecular level.