Benchtop Nuclear Magnetic Resonance Research Articles

Quantitative Component Analysis of Solid Mixtures by Analyzing Time Domain 1H and 19F T1 Saturation Recovery Curves (qSRC)

Prevalent polymorphism and complicated phase behavior of active pharmaceutical ingredients (APIs) often result in remarkable differences in the respective biochemical and physical API properties. Consequently, API form characterization and quantification play a central role in the pharmaceutical industry from early drug development to manufacturing. Here we present a novel and proficient quantification protocol for solid mixtures (qSRC) based on the measurement and mathematical fitting of T1 nuclear magnetic resonance (NMR) saturation recovery curves collected on a bench top time-domain NMR instrument. The saturation recovery curves of the relevant pure components are used as fingerprints. Employing a bench top NMR instrument possesses clear benefits. These instruments exhibit a small footprint, do not present any special requirements on lab space, and required sample handling is simple and fast. The qSRC analysis can easily be conducted in a conventional laboratory setting as well as in an industrial production environment, making it a versatile tool with the potential for widespread application. The accuracy and efficiency of the qSRC method is illustrated using 1H and 19F T1 data of selected pharmaceutical model compounds, as well as utilizing 1H T1 data of an actual binary API anhydrous polymorph system of a Merck & Co., Inc. compound formerly developed as a hepatitis C virus drug.

Process spectroscopy in microemulsions—setup and multi-spectral approach for reaction monitoring of a homogeneous hydroformylation process

Reaction monitoring in disperse systems, such as emulsions, is of significant technical importance in various disciplines like biotechnological engineering, chemical industry, food science, and a growing number other technical fields. These systems pose several challenges when it comes to process analytics, such as heterogeneity of mixtures, changes in optical behavior, and low optical activity. Concerning this, online nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for process monitoring in complex reaction mixtures due to its unique direct comparison abilities, while at the same time being non-invasive and independent of optical properties of the sample. In this study the applicability of online-spectroscopic methods on the homogeneously catalyzed hydroformylation system of 1-dodecene to tridecanal is investigated, which is operated in a mini-plant scale at Technische Universität Berlin. The design of a laboratory setup for process-like calibration experiments is presented, including a 500 MHz online NMR spectrometer, a benchtop NMR device with 43 MHz proton frequency as well as two Raman probes and a flow cell assembly for an ultraviolet and visible light (UV/VIS) spectrometer. Results of high-resolution online NMR spectroscopy are shown and technical as well as process-specific problems observed during the measurements are discussed.

Bringing NMR and IR Spectroscopy to High Schools

Development of benchtop, portable Fourier transform nuclear magnetic resonance (NMR) and infrared (IR) spectrometers has opened up opportunities for creating university–high school partnerships that provide high school students with hands-on experience with NMR and IR instruments. With recent changes to the international baccalaureate chemistry and advanced placement chemistry curricula, NMR and IR spectroscopy can be mapped directly to content that is already built into general, organic, and materials courses offered at the high school level. We developed a program in which the university provides professional development opportunities to high school chemistry teachers and further opportunities for these teachers to bring benchtop NMR and IR instruments directly into their own classrooms. This partnership not only benefits students by providing unique active learning experiences, but also offers opportunities for high school teachers’ professional development through on-campus training workshops. These p...

FoodPro: A Web-Based Tool for Evaluating Covariance and Correlation NMR Spectra Associated with Food Processes.

Foods from agriculture and fishery products are processed using various technologies. Molecular mixture analysis during food processing has the potential to help us understand the molecular mechanisms involved, thus enabling better cooking of the analyzed foods. To date, there has been no web-based tool focusing on accumulating Nuclear Magnetic Resonance (NMR) spectra from various types of food processing. Therefore, we have developed a novel web-based tool, FoodPro, that includes a food NMR spectrum database and computes covariance and correlation spectra to tasting and hardness. As a result, FoodPro has accumulated 236 aqueous (extracted in D2O) and 131 hydrophobic (extracted in CDCl3) experimental bench-top 60-MHz NMR spectra, 1753 tastings scored by volunteers, and 139 hardness measurements recorded by a penetrometer, all placed into a core database. The database content was roughly classified into fish and vegetable groups from the viewpoint of different spectrum patterns. FoodPro can query a user food NMR spectrum, search similar NMR spectra with a specified similarity threshold, and then compute estimated tasting and hardness, covariance, and correlation spectra to tasting and hardness. Querying fish spectra exemplified specific covariance spectra to tasting and hardness, giving positive covariance for tasting at 1.31 ppm for lactate and 3.47 ppm for glucose and a positive covariance for hardness at 3.26 ppm for trimethylamine N-oxide.

Determination of Alcohol Content in Alcoholic Beverages Using 45 MHz Benchtop NMR Spectrometer

Alcohol or ethanol is considered the most widely used recreational drug worldwide, and its production, consumption, and sale are strictly regulated by laws. Alcohol content of alcoholic beverages (wine, beers, and spirits) is about 3–50% v/v. Analytical methods to determine the alcohol content must be reliable, precise, and accurate. In this study, the amount of ethanol in several alcoholic beverages was determined using a 45 MHz low-field benchtop NMR (nuclear magnetic resonance) spectrometer. Internal standard and standard addition analytical methods were utilized to quantify ethanol. For both methods, acetic acid or acetonitrile was used as internal standard to quantify alcohol content by using the peak area corresponding to the methyl peaks of ethanol, acetic acid, or acetonitrile. Results showed that internal standard method gave values of percent alcohol that are in close agreement with the indicated label as confirmed by running the samples in a 400 MHz high-field NMR spectrometer using acetic acid as internal standard. This study demonstrates the utility of a benchtop NMR spectrometer that can provide an alternative technique to analyze percent alcohol in alcoholic products.

NMR Studies of the Effect of CO2 on Oilfield Emulsion Stability

Formation of water-in-crude oil emulsions is a pervasive problem for crude oil production and transportation. Here we investigate the effectiveness of a comparatively low pressure CO2 treatment in terms of breaking these water-in-crude oil emulsions. To this end, we used unique benchtop nuclear magnetic resonance (NMR) technology to measure the droplet size distribution (DSD) of the emulsions. Treatment with 50 bar CO2 for 2 h resulted in significant emulsion destabilization; this was replicated when CO2 was replaced by N2O, which has a solubility in both the aqueous and oil phases similar to that of CO2. Low solubility gases, N2 and CH4, by contrast had no effect on emulsion stability. Treatment with CO2 was also found to have no effect on a model water-in-paraffin oil emulsion stabilized by a synthetic surfactant (Span 80). Collectively, this supported the hypothesis that emulsion destabilization results from CO2 precipitation of asphaltenes as opposed to emulsion droplet film disruption during depressu...

Calibration of NMR Spectroscopy for Accurate Estimation of Oil Content in Sunflower, Safflower and Castor Seeds

Oil content analysis in oilseed crops requires methods that are non-destructive, accurate, fast, eco-friendly (without the use of solvent), inexpensive in terms of consumables, and easy to use. Pulsed low-resolution nuclear magnetic resonance (NMR) satisfies all these conditions. The objective of the present study was to develop an oil measurement method for seeds using NMR spectrometry. A bench-top pulsed NMR analyser was calibrated with respect to temperature. Six genotypes each of sunflower, safflower and castor were used for the analysis. Changes in sample conditioning temperature can lead to significant changes in the calibration graph. Based on the statistical parameters (correlation coefficient, variance and standard deviation) obtained, the best calibration was found for sunflower and safflower at 40°C and castor at 44°C among the temperature ranges tested.

Hydrate Shell Growth Measured Using NMR.

Benchtop nuclear magnetic resonance (NMR) pulsed field gradient (PFG) and relaxation measurements were used to monitor the clathrate hydrate shell growth occurring in water droplets dispersed in a continuous cyclopentane phase. These techniques allowed the growth of hydrate inside the opaque exterior shell to be monitored and, hence, information about the evolution of the shell's morphology to be deduced. NMR relaxation measurements were primarily used to monitor the hydrate shell growth kinetics, while PFG NMR diffusion experiments were used to determine the nominal droplet size distribution (DSD) of the unconverted water inside the shell core. A comparison of mean droplet sizes obtained directly via PFG NMR and independently deduced from relaxation measurements showed that the assumption of the shell model-a perfect spherical core of unconverted water-for these hydrate droplet systems is correct, but only after approximately 24 h of shell growth. Initially, hydrate growth is faster and heat-transfer-limited, leading to porous shells with surface areas larger than that of spheres with equivalent volumes. Subsequently, the hydrate growth rate becomes mass-transfer-limited, and the shells become thicker, spherical, and less porous.

Brute-Force Hyperpolarization for NMR and MRI.

Hyperpolarization (HP) of nuclear spins is critical for ultrasensitive nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). We demonstrate an approach for >1500-fold enhancement of key small-molecule metabolites: 1-(13)C-pyruvic acid, 1-(13)C-sodium lactate, and 1-(13)C-acetic acid. The (13)C solution NMR signal of pyruvic acid was enhanced 1600-fold at B = 1 T and 40 °C by pre-polarizing at 14 T and ∼2.3 K. This "brute-force" approach uses only field and temperature to generate HP. The noted 1 T observation field is appropriate for benchtop NMR and near the typical 1.5 T of MRI, whereas high-field observation scales enhancement as 1/B. Our brute-force process ejects the frozen, solid sample from the low-T, high-B polarizer, passing it through low field (B < 100 G) to facilitate "thermal mixing". That equilibrates (1)H and (13)C in hundreds of milliseconds, providing (13)C HP from (1)H Boltzmann polarization attained at high B/T. The ejected sample arrives at a room-temperature, permanent magnet array, where rapid dissolution with 40 °C water yields HP solute. Transfer to a 1 T NMR system yields (13)C signals with enhancements at 80% of ideal for noted polarizing conditions. High-resolution NMR of the same product at 9.4 T had consistent enhancement plus resolution of (13)C shifts and J-couplings for pyruvic acid and its hydrate. Comparable HP was achieved with frozen aqueous lactate, plus notable enhancement of acetic acid, demonstrating broader applicability for small-molecule NMR and metabolic MRI. Brute-force avoids co-solvated free-radicals and microwaves that are essential to competing methods. Here, unadulterated samples obviate concerns about downstream purity and also exhibit slow solid-state spin relaxation, favorable for transporting HP samples.

60 MHz卓上NMR装置を用いる有機化合物の純度測定の検討

Since quantitative values on the basis of a nucleus can be obtained by nuclear magnetic resonance (NMR) spectroscopy, the quantitative NMR technique requires no identical standard. For this reason, it is expected to be a universal quantitative method. However, the quantification using an NMR requires a high resolution NMR spectrometer in NMR measurement. In this paper, we discuss the quantitative NMR method using a benchtop NMR spectrometer with a low magnetic field. We studied the conditions of NMR measurement and data process. The precision of the result was evaluated with approximately 1% using a benchtop spectrometer. Especially, the low S/N and large FWHS of the NMR signals caused low repeatability.

NMR studies of emulsion microstructure approaching the phase inversion point

Bench-top Nuclear Magnetic Resonance (NMR) pulsed field gradient (PFG) methods were used to measure the droplet size distributions (DSD) of various water-in-oil (w/o) emulsions as their water content was increased towards the phase inversion point (PIP). Such concentrated, opaque emulsions are not readily interrogated with alternative droplet sizing techniques. However, monitoring of the DSD as the PIP is approached is needed to help establish how different potential mechanisms, such as divergence of mean droplet size and/or the formation of multiple emulsions, are involved in the inversion process. Two separate NMR spectrometers were used and found to give consistent results for the emulsion DSDs and their evolution as the PIP was approached. An exponential increase in mean emulsion droplet size was observed for various crude oil emulsion samples prepared by sequential droplet phase (water) addition under shear as the PIP was approached, which is consistent with the mechanism of droplet coalescence exceeding droplet break-up. However, for w/o emulsions consisting of a pure hydrocarbon liquid stabilized by artificial surfactants, no change in mean droplet size was observed as the PIP was similarly approached. The NMR data were also analyzed for the presence of multiple emulsions – these were distinctly evident in several samples but were of the local w/o/w type.

On-line monitoring of chemical reactions by using bench-top nuclear magnetic resonance spectroscopy.

Real-time nuclear magnetic resonance (NMR) spectroscopy measurements carried out with a bench-top system installed next to the reactor inside the fume hood of the chemistry laboratory are presented. To test the system for on-line monitoring, a transfer hydrogenation reaction was studied by continuously pumping the reaction mixture from the reactor to the magnet and back in a closed loop. In addition to improving the time resolution provided by standard sampling methods, the use of such a flow setup eliminates the need for sample preparation. Owing to the progress in terms of field homogeneity and sensitivity now available with compact NMR spectrometers, small molecules dissolved at concentrations on the order of 1 mmol L(-1) can be characterized in single-scan measurements with 1 Hz resolution. Owing to the reduced field strength of compact low-field systems compared to that of conventional high-field magnets, the overlap in the spectrum of different NMR signals is a typical situation. The data processing required to obtain concentrations in the presence of signal overlap are discussed in detail, methods such as plain integration and line-fitting approaches are compared, and the accuracy of each method is determined. The kinetic rates measured for different catalytic concentrations show good agreement with those obtained with gas chromatography as a reference analytical method. Finally, as the measurements are performed under continuous flow conditions, the experimental setup and the flow parameters are optimized to maximize time resolution and signal-to-noise ratio.

Optimized Droplet Sizing of Water-in-Crude Oil Emulsions Using Nuclear Magnetic Resonance

Water-in-crude oil emulsions are an increasing problem during production. Essential to any emulsion breaking method is an ability to accurately measure droplet size distributions; this is rendered extremely difficult given that the samples are both concentrated and opaque. Here, we systematically consider the use of a standard, low-field benchtop nuclear magnetic resonance (NMR) apparatus to accurately measure the droplet size distributions. Such measurements are challenging because the NMR signal from the oil phase erroneously contributes to the measured water droplet size distribution. Conventionally, the oil-phase signal is nulled-out based on differences in the NMR T1 relaxation parameter between water and oil. However, in the case of crude oil, the oil presents a broad T1 distribution, rendering this approach infeasible. On the basis of this oil T1 distribution, we present an optimization routine that adjusts various NMR measurement timing parameters [observation time (Δ) and inversion time (Tinv)] to effectively eliminate this erroneous crude oil contribution. An implementation of this optimization routine was validated against measurements performed using unambiguous chemical-shift selection of the water (droplet) signal, as would conventionally be provided by high-field superconducting NMR spectrometers. We finally demonstrate successful droplet sizing of a range of water-in-crude oil emulsions.

A non-invasive study of flow dynamics in membrane distillation hollow fiber modules using low-field nuclear magnetic resonance imaging (MRI)

Low-field bench-top nuclear magnetic resonance imaging (MRI) has been applied to investigate the hydrodynamics in novel hollow fiber modules with four different configurations of randomly-packed, spacer-knitted, curly and semi-curly fibers, specifically designed for the membrane distillation (MD) process. Imaging, spatially resolved velocity maps and propagators (probability distributions of displacement/velocity) were all acquired in the modules with flow in the shell side. The MRI data were correlated with overall module performance.The results have revealed that the curly configuration exhibited more significant transverse flow and hence enhanced mixing, compared to the randomly packed configuration; this was consistent with an enhanced MD performance in terms of permeation flux. Interestingly, the velocity maps of the spacer-knitted fiber design indicated a significant flow channeling in the center of the module, despite its enhanced MD performance. Fortunately, combined with further investigations on the localized velocity images of this configuration, the acquisition of propagators provided valuable information in revealing the existence of reduced stagnant regions and significant transverse flow at varied operating conditions, which indicated a better overall mixing and hence confirmed its module performance.

Use of bench-top NMR to measure the density, composition and desorption isotherm of C–S–H in cement paste

1H nuclear magnetic resonance (NMR), supported by a measurement of the degree of hydration using X-ray diffraction, has been used to fully characterise the nano-scale porosity and composition of calcium–silicate–hydrate (C–S–H), the active component of cement. The resultant “solid” density and composition are ρ=2.68g/cm3; (Ca)1.53. (Si0.96,Al0.04)O3.51. (H2O)1.92 for an underwater cured, never-dried cement paste with an initial mix water-to-cement ratio of 0.4 after 28days of hydration. In addition, the first pore-type resolved desorption isotherm of cement that shows the location of water as a function of relative humidity has been measured. Critical to our results is verification of the assignment of the different NMR spin–spin relaxation time components. These have been corroborated with conventional analyses. The new methodology is key to enabling design of cement pastes with lower environmental impact.

Determination of mean droplet sizes of water-in-oil emulsions using an Earth’s field NMR instrument

The use of the Earth’s magnetic field (EF) to conduct nuclear magnetic resonance (NMR) experiments has a long history with a growing list of applications (e.g. ground water detection, diffusion measurements of Antarctic sea ice). In this paper we explore whether EFNMR can be used to accurately and practically measure the mean droplet size (〈a〉) of water-in-oil emulsions (paraffin and crude oil). We use both pulsed field gradient (PFG) measurements of restricted self-diffusion and T2 relaxometry, as appropriate. T2 relaxometry allows the extension of droplet sizing ability below the limits set by the available magnetic field gradient strength of the EFNMR apparatus. A commercially available bench-top NMR spectrometer is used to verify the results obtained using the EFNMR instrument, with good agreement within experimental error, seen between the two instruments. These results open the potential for further investigation of the application of EFNMR for emulsion droplet sizing.

Nuclear Magnetic Resonance: A Tool for Malaria Diagnosis?

Malaria control can be improved by rapid, sensitive, low-cost detection of infection. Several such strategies are being pursued. Rapid diagnostic tests can detect infections at parasite densities above 200 μL(-1). Polymerase chain reaction methods can detect low parasite densities, but are slow and prone to contamination under field conditions. Methods that detect hemozoin presence in blood have been proposed as alternatives for rapid detection of infection. In this study, we used a benchtop nuclear magnetic resonance (NMR) device to detect hemozoin. This device could be deployed in malaria-endemic settings. We measured synthetic hemozoin in phosphate-buffered saline and malaria parasites in human blood. The NMR detected hemozoin in suspensions of 4 ng μL(-1) and parasites at densities of 8,000-10,000 μL(-1) (0.2% parasitemia). Thus, our preliminary NMR approach, although providing very rapid measurements, is unlikely to achieve the required sensitivity and specificity for malaria diagnosis, unless a preliminary concentration step is performed.

Magnetic nanoparticle biosensors

One of the major challenges in medicine is the rapid and accurate measurement of protein biomarkers, cells, and pathogens in biological samples. A number of new diagnostic platforms have recently been developed to measure biomolecules and cells with high sensitivity that could enable early disease detection or provide valuable insights into biology at the systems level. Most biological samples exhibit negligible magnetic susceptibility; therefore, magnetic nanoparticles have been used for diverse applications including biosensing, magnetic separation, and thermal ablation therapy. This review focuses on the use of magnetic nanoparticles for detection of biomolecules and cells based on magnetic resonance effects using a general detection platform termed diagnostic magnetic resonance (DMR). DMR technology encompasses numerous assay configurations and sensing principles, and to date magnetic nanoparticle biosensors have been designed to detect a wide range of targets including DNA/mRNA, proteins, enzymes, drugs, pathogens, and tumor cells. The core principle behind DMR is the use of magnetic nanoparticles as proximity sensors that modulate the spin-spin relaxation time of neighboring water molecules, which can be quantified using clinical MRI scanners or benchtop nuclear magnetic resonance (NMR) relaxometers. Recently, the capabilities of DMR technology were advanced considerably with the development of miniaturized, chip-based NMR (microNMR) detector systems that are capable of performing highly sensitive measurements on microliter sample volumes and in multiplexed format. With these and future advances in mind, DMR biosensor technology holds considerable promise to provide a high-throughput, low-cost, and portable platform for large scale molecular and cellular screening in clinical and point-of-care settings.

Investigation of Hydrogenation of Toluene to Methylcyclohexane in a Trickle Bed Reactor by Low-Field Nuclear Magnetic Resonance Spectroscopy

Low-field nuclear magnetic resonance (NMR) spectroscopy is applied to study the hydrogenation of toluene in a lab-scale reactor. A conventional benchtop NMR system was modified to achieve chemical shift resolution. After an off-line validity check of the approach, the reaction product is analyzed on-line during the process, applying chemometric data processing. The conversion of toluene to methylcyclohexane is compared with off-line gas chromatographic analysis. Both classic analytical and chemometric data processing was applied. As the results, which are obtained within a few tens of seconds, are equivalent within the experimental accuracy of both methods, low-field NMR spectroscopy was shown to provide an analytical tool for reaction characterization and immediate feedback.

Coating thickness of magnetic iron oxide nanoparticles affects R2 relaxivity

To evaluate the effect of coating thickness on the relaxivity of iron oxide nanoparticles. Monocrystalline superparamagnetic iron oxide nanoparticles (MIONs), coated with a polyethylene glycol (PEG)-modified, phospholipid micelle coating, with different PEG molecular weights, were prepared. The particle diameters were measured with dynamic light scattering (DLS) and electron microscopy (EM). The R1 and R2 of MIONs were measured using a bench-top nuclear magnetic resonance (NMR) relaxometer. pH was varied for some measurements. Monte Carlo simulations of proton movement in a field with nanometer-sized magnetic inhomogeneities were performed. Increasing the molecular weight of the PEG portion of the micelle coating increased overall particle diameter. As coating thickness increases, the R2 decreases and the R1 increases. Changing pH has no effect on relaxivity. The Monte Carlo simulations suggest that the effect of coating size on R2 relaxivity is determined by two competing factors: the physical exclusion of protons from the magnetic field and the residence time for protons within the coating zone. Coating thickness can significantly impact the R2, and the R2/R1 ratio, of a MION contrast agent. An understanding of the relationship between coating properties and changes in relaxivity is critical for designing magnetic nanoparticle probes for molecular imaging applications using MRI.