Several topics in the realm of Nuclear Magnetic Resonance (NMR) spectroscopy are discussed in this dissertation. These topics can be divided into two major sections. The first section considers the treatment of data from standard NMR relaxation and diffusion experiments. The current standard for the analysis of transients in low-field NMR is the Inverse Laplace Transform (ILT). Often leading to an inconsistency in the stability of results, the ILT tends to be an ill-posed problem like many other inversion methods. Alternative data processing methods have recently been introduced in an attempt to improve the resolution, stability, and accuracy of results for both discrete and continuous sets of recovered constants. The application of the Matrix Pencil Method (MPM), a generalized eigenvalue-based algorithm, to NMR transients has recently gained traction as a reliable processing method with low computational costs. Here, the MPM is first extended to the resolution and quantitative analysis of multiple longitudinal (T1) relaxation components from data acquired by a stray-field sensor. A comparison of MPM to ILT is conducted by testing several combinations of Gd3+-doped 0.9% saline samples with an array of concentrations. It is shown that MPM not only has a greater ability to resolve than ILT at low SNR, but the resulting time constants and relative component weights are also closer to their expected values. The results of the stray-field study brings about two questions: What are the true limitations of the MPM resolution capabilities and how can experiments be optimized to gain the most information possible from the data? The MPM provides exact solutions for noise-free transients with few discrete components. These solutions increasingly deviate as the SNR of the transient decreases. Numerical and analytical methods are developed to use this knowledge at a given SNR to predict the prime sampling interval to obtain the maximum resolution and accuracy possible. The second major section concerns the effects of spatial confinement on diffusion and chemical exchange. Two-site exchange has been exhaustively studied and its dynamics are well understood. Three-site exchange, on the other hand, is a drastically different story. Recent kinetics studies on three-site systems have revealed asymmetric exchange behavior when subjected to restrictive environments. This asymmetry is indicative of a violation of detailed balance which states that all pairs of relaxation sites should experience equivalent exchange at thermal equilibrium. An investigation on the effects of confinement on three-site exchange is conducted using two 2D numerical methods, a Monte-Carlo vacancy diffusion simulation and a molecular dynamics gas diffusion simulation with elastic particles. These simulations reveal that this asymmetry indeed arises when the diffusive motion is driven away from standard Brownian dynamics. Under this driven equilibrium, a circular flux between relaxation sites develops which goes against detailed balance. The cyclical diffusive behavior potentially arises from the excitation of the diffusive eigenmodes of a pore.

Nuclear magnetic resonance (NMR) is a powerful chemometric method for any scientist because it is easily translated to a portable format. Recent advances have made portable NMR spectroscopy economically and practically feasible. Here, the foundational physics of spin dynamics is discussed as a bridge from the abstract theory of NMR to practical applications of low field relaxometry. Relaxometry can provide a window into the molecular dynamics of a system through measurement of spin relaxation rates, which directly relate to chemical interactions and mobility within a system.The ease with which it can be customized makes portable NMR an extremely desirable technique for non-destructive, quantitative chemical analysis. However, portable NMR obtains a weaker signal with decreased resolution compared to traditional NMR. This is because spin states are not strongly split in low magnetic fields and are therefore populated nearly equally at thermodynamic equilibrium, causing weak longitudinal magnetization. As such, one typically measures exponential decay constants at low field rather than frequencies. Filtering and data analysis are considered with the development of the matrix pencil method (or MPM, so named after the mathematical entity which it employs) as a tool to aid in studies of low signal-to-noise systems and complex materials. Here, the MPM is explored first as a filtering strategy, and second, as a stable, reproducible data processing method in low field NMR. Currently, the inverse Laplace transform (ILT) is the conventional method for processing data in low field NMR. However, the ILT is hindered by sensitivity to noise, poor resolution, and high computational requirements that make it difficult to apply in non-laboratory environments. Improving the efficiency of data processing could expand the applications of portable NMR and enhance the quality of information gained from correlation experiments. The MPM fits in a broad category of filter diagonalization methods for digital signal analysis, and was developed for use in radar, antenna, and acoustics technologies. The success of the MPM in other areas of signal processing makes its application to low field NMR promising. The latter half of this dissertation describes some applications of portable NMR by coupling hardware innovations with a creative data processing strategy. First, a hospital-based measurement of blood plasma water content is developed. Next, factory-based analysis of rheological properties is presented. Finally, the use of portable high-field NMR is established for metabolomic-type assays in agricultural and environmental studies.

Without a doubt, nuclear magnetic resonance (NMR) has been an indispensable tool forstructural determination in chemistry, molecular biology, and more. The power of NMR to elucidate positions and distances of atoms within molecules has allowed generations of chemists, chemical biologists, and molecular biologists to develop strategies for synthesizing new medicines, advanced materials, and to verify their syntheses. To this day, the core strategy from which this tool draws its power remains a drive to higher and higher magnetic field. For the purposes described above, it has been a necessary drive. A higher field allows for better signal to noise ratio (S/N) and narrows relative spectral linewidths, resulting in faster data acquisitions and for acquired data to be more granulated. There are, however, side effects that accompany the drive to higher field. Extremely strong magnetic fields are physically dangerous if any magnetizable materials come close enough to magnets. Equipment, tools, and some people themselves must therefore be kept a safe distance away, and instances where failures in this regard have led to deaths are not unheard of. The superconducting magnets that generate these intense fields are also quite large, are limited to tiny sample volumes, and require special maintenance, which can be expensive. Specifically, they require a constant supply of liquid helium in order to keep the coils at temperatures low enough to maintain their superconducting characteristics. This helium is not a renewable or ubiquitous resource and it gets more expensive by the year, as challenges to exploration, capture, and even political upheaval destabilize the global market for liquid helium. Meanwhile, advances in amplifier and NMR spectrometer technology have resulted in better control and sensitivity in low-field experiments. For these reasons, and more, low-field NMR has become an ever-more attractive area of research for the advancement of NMR and magnetic resonance in general.

This work describes a body of research focused on design and data analysis for low-fieldNMR, which is loosely defined for the purposes of this manuscript as NMR performed in a static magnetic field, B0, less than 0.1 T, or a Larmor frequency lower than about 4.4 MHz. Because NMR at low-field does not generally produce chemical shift-resolved spectra, data acquisition and analysis instead tends to focus on bulk magnetic relaxation rates and imaging. Furthermore, these parameters are often difficult to understand using direct mathematical models because samples investigated at low-field are often inhomogeneous and possess geometries that are not always amenable to symmetry-based mathematical simplifications. It is often better to instead use statistical correlation and categorization to understand experimental results from a higher, less granular level. This fact motivates an initial exploration into the use of partial least squares as a method to determine the electrical permittivity of aqueous electrolyte samples at extremely high pressures. While this is not a study of magnetic resonance, it serves as an example for the application of this technique to similar problems that might present themselves in NMR. The next chapter describes Matlab codes that have been written for simulating magnetic fields for arbitrary coil and magnet shapes. The final two chapters are an exploration into novel rf coil designs for use in single-sided NMR, and specifically in the presence of shielding due to conductive magnet material. Multiple coil designs are described and their performances characterized. Ultimately an unexpected “fringe coil” geometry is shown to be far superior in theoretical models and practical testing with a variety of sample types and geometries.

Lithium-ion batteries provide lightweight, energy dense, and efficient power for portable electronics and electric vehicles. Accompanying the rise of lithium battery technology is the need for fast, non-destructive diagnostic techniques to determine important battery performance or safety parameters. Low-field NMR and relaxometry is an ideal technique to probe lithium-ion polymer (LiPo) batteries due to its ability to penetrate the aluminum casing of these batteries. The development of a few different low-field techniques are presented here to measure different battery parameters. This includes measuring the T_1 and T_2 relaxation times of LiPo batteries at differing states of charge, magnetic resonance imaging showing T_2 as a function of position across a battery, and using pulsed field gradient 7Li nuclear magnetic resonance (NMR) to measure Li diffusion coefficients.

Many industrial manufacturing processes are moving towards continuous production methods. These methods typically involve flowing liquids or moving materials from one step of the process to another continuously, as opposed to traditional, batch production where steps of the process occur in large immobile containers. The use of continuous manufacturing methods in chemical products, for example, is highly desirable, as increases in product yields and higher energy efficiencies are achieved. When designed and correctly implemented, these methods typically require less interaction with people and improve product quality control. With continuous manufacturing comes the need for inline process monitoring and control. This is typically performed with simple sensors (pressure, temperature, flow meters) or with advanced analytical devices. Together, the sensors and devices fall under the classification of a process analytical technology (PAT). The use of PATs is essential in success of continuous manufacturing processes, and advancements in spectroscopic PATs specifically allows for the implementation of new continuous manufacturing processes in historically batch-mode industries. Substantial development and use of spectroscopic PATs in continuous production has already happened with Raman and infrared spectroscopies. Nuclear magnetic resonance (NMR) PATs, however, have lagged behind these other spectroscopies. This is largely because much of the innovation in NMR has pushed the technology into using large, expensive, high-field, cryogenic magnets. These instruments, while powerful for molecular studies, are ill-equipped for in-line industrial environments. The samples studied with these instruments must conform to the geometric limitations of the instruments, and the instruments themselves cannot be near any

ferromagnetic materials. Lower field benchtop systems have another set of issues, as they are limited to small sample volumes and low fluid velocities. Finally, most of these systems are concerned with analyzing the sample on a molecular level, which is completely useless for studying complex aqueous mixtures during process. This work details the efforts involved in advancing the use of portable NMR relaxometry for process monitoring in flowing aqueous industrial systems. NMR relaxometry is advantageous for monitoring flowing systems as it is nondestructive, can be used to study complex mixtures inside pipes of various metal and plastic materials, and does not require a large superconducting magnet. Unfortunately, the technique does suffer from low signal to noise ratios and has limited past development for in-line industrial systems. Nevertheless, NMR relaxometry has the potential to be an inexpensive, powerful PAT once the development work is done. Chapter one discusses the fundamentals of NMR and describes two common pulse sequences for measuring the relaxation properties of protons. Chapter two shows evidence supporting the use of NMR relaxometry measurements for process monitoring of biomass pretreatment by ultrasound cavitation. The results show that relaxometry measurements are indicative of process outcomes, and that the measurements can be performed during flow. Successful performance of the measurements during flow is needed because the scale up process of cavitation pretreatment switches from ultrasound batch-mode to hydrodynamic flow-mode cavitation. Chapter three addresses the issues associated with performing NMR measurements on systems undergoing turbulent flow. A turbulent aqueous environment is the ideal industrial

system to study since water is the preferred solvent in most cases, yet most established NMR protocols fail to give useful information in these environments. This chapter explores alternative and forgotten techniques that work well in turbulent aqueous environments. The chapter concludes with examples of using these techniques to monitor aqueous sawdust extraction with hydrodynamic cavitation. Chapter four proposes a 3D printed solution to address the low signal to noise issue associated with using NMR relaxometry to study fast flowing aqueous systems. Details for a portable, industrial ready system are shown, along with attempts to use Earth’s magnetic field in place of a permanent magnet for analysis.

Instrumentation is the bedrock of spectroscopic investigation regardless of the location on the electromagnetic spectrum being studied. Although X-ray spectroscopy and Nuclear Magnetic Resonance (NMR) spectroscopy rely on different energies of electromagnetic waves, the goal of both types of spectroscopies is to use electromagnetic waves to excite an atom and to measure the resulting perturbation. X-ray nanochemistry follows the physical and chemical interactions between high energy photons used to excite electrons and the resulting chemical reactions from the electron depositing energy into the surrounding medium. These interactions are measured using chemical dosimeters, but can also be studied through calculations based on physical interactions. To improve the effectiveness of these studies, new instrumentation has been developed to control the location of X-rays to increase the dose enhancement at a specific location. This instrument can also be improved by using X-ray calculations that model sample dosimetry produced by an algorithm giving more accurate results. In Chapter 2, the development and implementation of an improved scanning focusing X-ray source with a variable focal length for extremely high dose enhancement of a sample containing AuNPs is discussed. In Chapter 3, calculations to simulate the scanning focusing instrument from Chapter 2 are demonstrated to accurately simulate the beam intensity, shape, and dose profile measured by the instrument.Solid state NMR uses the rapid spinning of a solid sample at 54.74° in order to acquire spectra that would otherwise not be measurable in a static state using a process called magic angle spinning (MAS) [1,2]. This spinning uses specialized and expensive equipment. To improve the sampling signal for a low cost, widely available instrument, a 3D printed MAS rotor was developed. This device improves the signal from solid KBr and NaBr to produce narrow linewidths that improve sampling signal. To further improve upon the existing spectroscopic method, the device was modified to allow for up to 8 samples to be measured simultaneously. This gives the instrument the ability to measure samples that it was otherwise unable to analyze for a few dollars per unit. In Chapter 4, the development of a 3D printed MAS probe for a low field NMR instrument is shown and the 3D printing techniques used to improve signal acquisition through a multiple stator design are demonstrated.

A high-volume, high-pressure nuclear magnetic resonance (NMR) probe was developed to be amenable to realistic samples and accommodated by a variety of low-field magnetic assemblies. This high volume, pressure probe was made in response to existing high-pressure probes that could not accommodate samples in excess of a couple milliliters. Initial research with industrial samples of petrol and biomass pretreatment showed that current high-pressure NMR assemblies were not amenable to research with heterogeneous industrial samples, due to their high cost and low volume. The high-pressure NMR probe discussed here was assembled from commercially available parts, modifying a pressure reactor to incorporate a high-pressure NMR probe and circuit assembly. This probe was developed and tested using single-sided, portable magnets. Using relaxometry, rather than resolved chemical shifts, due to the lowered frequency range, macroscopic properties of liquids and mixtures could be observed in real time over the course of pressurization. This work on the high-pressure probe allowed the study of mass-transport mechanisms of salts into a food matrix. Magnetic resonance images (MRI) were taken as apple flesh became pressure-impregnated with salts. These images were used to mathematically model the infusion of molecules into food matrices at high pressure, a feat that had not previously been achieved due to the lack of appropriate high-pressure analytical NMR instrumentation. This information is important in the field of food science where mass transport mechanisms in high-pressure assisted infusion have yet to be fully understood. In addition to the previously mentioned magnetic assemblies, this pressurization probe was interfaced to an opposing pole-facing magnet, an Aspect Instruments imaging magnet, and a SMIS electromagnet. The high-pressure probe was built for high-volume heterogeneous samples. The probe proved robust enough to perform magnetic resonance (MR) relaxometry on other isotopes like sodium, 23Na.