Benchtop NMR Spectrometer Research Articles

Recent Applications of Benchtop Nuclear Magnetic Resonance Spectroscopy

Benchtop nuclear magnetic resonance (NMR) spectroscopy uses small permanent magnets to generate magnetic fields and therefore offers the advantages of operational simplicity and reasonable cost, presenting a viable alternative to high-field NMR spectroscopy. In particular, the use of benchtop NMR spectroscopy for rapid in-field analysis, e.g., for quality control or forensic science purposes, has attracted considerable attention. As benchtop NMR spectrometers are sufficiently compact to be operated in a fume hood, they can be efficiently used for real-time reaction and process monitoring. This review introduces the recent applications of benchtop NMR spectroscopy in diverse fields, including food science, pharmaceuticals, process and reaction monitoring, metabolomics, and polymer materials.

Quantitative frother analysis on coal mine process water with a benchtop NMR spectrometer

This paper investigates the use of a benchtop NMR for quantification of a commonly used frothing agent, methyl isobutyl carbinol (MIBC) in the process water of a coal preparation facility. Solid phase extraction is used to increase the concentration of MIBC in the sample so that it is quantifiable by a benchtop NMR. A polymeric, reversed phase column with methanol as solvent gives a MIBC recovery rate of 67 ± 4% as determined using 400 MHz high-field NMR. The recovery rate consistently falls in the above narrow range even in the presence of diesel and inorganic electrolytes which are likely present as background chemicals in the process water. Using the average MIBC recovery rate, we use a quantum mechanical model to analyse the intensity of MIBC in the benchtop spectra. The quantum mechanical modelling algorithm effectively excludes the effect of the diesel on the measured NMR signal. The quantification error when the inlet concentration of MIBC is between 1 and 12 mg/L (1.2–15 ppm v/v), is within 0.5 mg/L (0.6 ppm v/v).

Quantitative analysis of wine and other fermented beverages with benchtop NMR

We present a fully automated approach for quantitative compositional analysis of fermented beverages using benchtop nuclear magnetic resonance (NMR) spectroscopy. NMR spectroscopy, renowned for its applications in chemical structure elucidation, is gaining attention as a quantitative analytical technique due to its inherent linearity and the ability to obtain comprehensive quantitative information with a single simple experiment. Recently developed benchtop NMR spectrometers offer the quantitative capabilities of NMR to a wide range of potential users in industry, but their applicability has been limited by the reduced effective spectral resolution and the need for more advanced data processing. We address this problem with a model-based algorithm that hinges on the well-understood description of quantum mechanical phenomena in NMR spectroscopy. We demonstrate the effectiveness of our approach on a challenging problem of analysing the composition of wine and related fermented beverages – an important potential niche application of quantitative NMR. We successfully quantify more than 15 major components in the wine matrix and enable the quantification of species whose analysis is generally not possible with established methods. The average discrepancy of the obtained concentrations, when compared to the traditional methods of analysis, usually does not exceed 10% and is lower for the most abundant species (e.g. below 5% for ethanol).

Benchtop nuclear magnetic resonance spectroscopy in forensic chemistry.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique well known for its ability to elucidate structures and analyse mixtures and its quantitative nature. However, the cost and maintenance of high field NMR instruments prevent its widespread use by forensic chemists. The introduction of benchtop NMR spectrometers to the market operating at 40-80 MHz have a small footprint, are easy to use and cost much less than high field instruments, which makes them well suited to meet the needs of forensic chemists. These modern low field spectrometers are often capable of running multiple nuclei including 1 H, 13 C, 19 F and 31 P; 2D NMR experiments and advanced experiments such as solvent suppression and diffusion-ordered spectroscopy (DOSY) are possible. This has resulted in a number of publications in the area of forensic chemistry using benchtop NMR spectroscopy in the last 5 years that was previously missing from the literature. This mini review summarises this research including examples of benchtop NMR being used to identify and quantify compounds relevant to forensics and some advanced methods that may be used to overcome some of the limitations of these instruments for forensic analysis. Further validation and automation are likely required for widespread uptake of benchtop NMR in industry; however, it has been demonstrated as a useful complement to other analytical techniques commonplace of forensic laboratories.

RotoMate: An open-source, 3D printed autosampler for use with benchtop nuclear magnetic resonance spectrometers

Benchtop nuclear magnetic resonance (NMR) spectrometers are versatile analytic instruments with low acquisition and operation cost. However, in the basic version, samples must be manually measured one after the other. We herein describe the open-source autosampler RotoMate that allows the automated operation of such instruments. The hardware is easily assembled from 3D-printed and inexpensive off-the-shelf parts, and is controlled by an Arduino Uno. A software package interlinks the operation of the autosampler with the software of the NMR spectrometer and the software for the processing of the spectra. Experiments for up to 30 samples can be inserted into an interactive sample list. The autosampler automatically inserts and ejects the samples, initiates measurements on the spectrometer according to parameters specified in the sample list, and interacts with a common NMR software in the processing and visualization of the obtained spectroscopic raw data. If an internal standard is present, conversions and yields of chemical reactions are automatically calculated, enabling e.g. the monitoring of reactions. The device was fitted to a Magritek Spinsolve instrument and can interact with a free academic version of ACD NMR software to process the spectra, but can likely be adapted to similar instruments and spectroscopy software packages.

High Flow-Rate Benchtop NMR Spectroscopy Enabled by Continuous Overhauser DNP.

Analysis of a fast-flowing liquid with NMR spectroscopy is challenging because short residence times in the magnetic field of the spectrometer result in inefficient polarization buildup and thus poor signal intensity. This is particularly problematic for benchtop NMR spectrometers because of their compact design. Therefore, in the present work, different methods to counteract this prepolarization problem in benchtop NMR spectroscopy were studied experimentally. The tests were carried out with an equimolar acetonitrile + water mixture flowing through a capillary with a 0.25 mm inner diameter at flow rates up to 2.00 mL min-1, corresponding to mean velocities of up to 0.7 m s-1. Established approaches gave only poor results at high flow rates, namely, using a prepolarization magnet, using a loopy flow cell, and using a T1 relaxation agent. To overcome this, signal enhancement by Overhauser dynamic nuclear polarization (ODNP) was used, which is based on polarization transfer from unpaired electron spins to nuclear spins and happens on very short time scales, resulting in high signal enhancements, also in fast-flowing liquids. A corresponding setup was developed and used for the studies: the line leading to the 1 T benchtop NMR spectrometer first passes through a fixed bed with a radical matrix placed in a Halbach magnet equipped with a microwave cavity to facilitate the spin transfer. With this ODNP setup, excellent results were obtained even for the highest studied flow rates. This shows that ODNP is an enabler for fast-flow benchtop NMR spectroscopy.

Versatile high-pressure gas apparatus for benchtop NMR: Design and selected applications

A simple, yet highly versatile setup is presented for benchtop NMR analyses of gases at high-pressure. It consists mostly of commercial parts and includes multiple safety features while maintaining a small size to fit into a 1.20 m wide fume hood. Pressures up to 200 bar can be adjusted independently of the sample gas-bottle pressure in a matter of seconds. Mixtures of multiple gases can be produced in situ in a mixing chamber, which also serves to adjust the pressure. The high-pressure hardware and benchtop NMR spectrometer have been tested for long-term stability and repeatability of the measurements. The versatility of the setup is demonstrated by analyzing hydrocarbon-gas with attention to linewidths as well as their 1H relaxation times, by improving the resolution of 1H NMR spectra from solid polymers with pressurized CO2, and by visualizing the ingress of gaseous and supercritical methane into liquid benzene.

RotoMate: An open-source, 3D printed autosampler for use with benchtop nuclear magnetic resonance spectrometers

RotoMate: An open-source, 3D printed autosampler for use with benchtop nuclear magnetic resonance spectrometers

Commentary: Iconoclastic Reflections on the ‘Safety’ of Polyunsaturated Fatty Acid-Rich Culinary Frying Oils: Some Cautions regarding the Laboratory Analysis and Dietary Ingestion of Lipid Oxidation Product Toxins

Continuous or frequent ingestion of fried foods containing cytotoxic/mutagenic/genotoxic lipid oxidation products (LOPs) may present significant human health risks; such toxins are generated in thermally stressed polyunsaturated fatty acid (PUFA)-rich culinary frying oils (CFOs) during standard frying practices. Since monounsaturated and saturated fatty acids (MUFAs and SFAs, respectively) are much less susceptible to peroxidation than PUFAs, in this study CFOs of differential unsaturated fatty acid contents were exposed to laboratory-simulated shallow-frying episodes (LSSFEs). Firstly, we present a case study exploring the time-dependent generation of aldehydic LOPs in CFO products undergoing LSSFEs, which was then used to evaluate the relative potential health risks posed by them, and also to provide suitable recommendations concerning their safety when used for frying purposes. Sunflower, rapeseed, extra-virgin olive and coconut oils underwent LSSFEs at 180 °C: Samples were collected at 0–90 min time-points (n = 6 replicates per oil). Aldehydes therein were determined by high-resolution 1H NMR analysis at 400 and 600 MHz operating frequencies. For one of the first times, CFO LOP analysis was also performed on a non-stationary 60 MHz benchtop NMR spectrometer. 1H NMR analysis confirmed the thermally promoted, time-dependent production of a wide range of aldehydic LOPs in CFOs. As expected, the highest levels of these toxins were produced in PUFA-rich sunflower oil, with lower concentrations formed in MUFA-rich canola and extra-virgin olive oils; in view of its very high SFA content, only very low levels of selected aldehyde classes were generated in coconut oil during LSSFEs. Secondly, 1H NMR results acquired are discussed with regard to the suitability and validity of alternative, albeit routinely employed, spectrophotometric methods for evaluating the peroxidation status of CFOs and lipid-containing foods. Thirdly, an updated mini-review of the toxicological properties of and intake limits for LOPs, and deleterious health effects posed by their ingestion, is provided. In conclusion, exposure of PUFA-rich CFOs to high-temperature frying practices generates very high concentrations of aldehydic LOP toxins from thermally promoted, O2-powered, recycling peroxidation processes; these toxins penetrate into and hence are ‘carried’ by fried foods available for human consumption. Such toxins have the capacity to contribute towards the development and progression of non-communicable chronic diseases (NCDs) if cumulatively ingested by humans.

Incorporating Benchtop NMR Spectrometers in the Undergraduate Lab: Understanding Resolution and Circumventing Second-Order Effects

Nuclear magnetic resonance (NMR) spectroscopy is commonly introduced to students in the classroom, but its hands-on use in undergraduate laboratories is far less common. The significant costs to purchase and maintain a traditional high-field NMR spectrometer means that many institutions cannot offer this service to their students. Benchtop NMR spectrometers represent a very powerful alternative at a fraction of the cost and laboratory footprint. However, concerns about resolution and managing second-order effects can hamper its incorporation into the undergraduate curricula. Herein, we describe how resolution at the benchtop level differs from traditional high-field instruments and provide a thorough, tabulated list of 204 molecules which exhibit little to no second-order effects at the lower magnetic fields utilized in benchtop NMR spectroscopy.

Solvent suppression techniques for coupling of size exclusion chromatography and 1H NMR using benchtop spectrometers at 43 and 62 MHz

The characterisation of polymeric materials in their full complexity of chain length, monomeric composition, branching and functionalization is a tremendous challenge and is best tackled by tailored multi-dimensional coupled analytical and detection techniques. Herein, we focus on the improvement of an affordable but information rich 2D-method for polymer analysis: the online hyphenation of benchtop 1H NMR spectroscopy with size exclusion chromatography (SEC). The main benefit of this approach is correlated information of chain length (SEC) to chemical composition (1H NMR). Our setup combines SEC onflow with a benchtop NMR spectrometer at 43 or 62 MHz with chemical shift resolution as a robust detector. A detailed comparison of the two instruments is included considering, that only the 43 MHz instrument is equipped with a dedicated z-gradient enabling pulse sequences such as WET.The main challenge of this method is the very low concentration of species of interest after chromatographic separation. At typical SEC conditions, the analyte dilution is typically more than a factor of 1000:1 in a protonated solvent. Therefore, an efficient solvent signal suppression is needed. In this article, several suppression pulse sequences are explored like WET, WEFT, JNR and a simple one-pulse approach – some for the first time on this hardware. By choosing an optimal method, signal strength ratios of solvent to analyte of 1:1 or better are achievable on flow.To illustrate the broad range of possible applications, three typical cases of analyte to solvent signal proximity (no overlap, partial and full overlap) are discussed using typical polymers (PS, PMMA, PEMA) and solvents (chloroform and THF). For each case, several suppression methods are compared and evaluated using a set of numerical criteria (analyte signal suppression and broadening, solvent signal suppression, remaining solvent signal width).

Zero- to Ultralow-Field NMR Spectroscopy of Small Biomolecules.

Nuclear magnetic resonance (NMR) spectroscopy is a well-established analytical technique used to study chemicals and their transformations. However, high-field NMR spectroscopy necessitates advanced infrastructure, and even cryogen-free benchtop NMR spectrometers cannot be readily assembled from commercially available components. We demonstrate construction of a portable zero-field NMR spectrometer employing a commercially available magnetometer and investigate its applications in analytical chemistry. In particular, J-spectra of small representative biomolecules [13C]-formic acid, [1-13C]-glycine, [2,3-13C]-fumarate, and [1-13C]-d-glucose were acquired, and an approach relying on the presence of a transverse magnetic field during the detection was investigated for relaxometry purposes. We found that the water relaxation time strongly depends on the concentration of dissolved d-glucose in the range of 1-10 mM suggesting opportunities for indirect assessment of glucose concentration in aqueous solutions. Extending analytical capabilities of zero-field NMR to aqueous solutions of simple biomolecules (amino acids, sugars, and metabolites) and relaxation studies of aqueous solutions of glucose highlights the analytical potential of noninvasive and portable ZULF NMR sensors for applications outside of research laboratories.

Discovery and validation of an NMR-based metabolomic profile in urine as TB biomarker

Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.

Low-field benchtop NMR spectroscopy as a potential non-stationary tool for point-of-care urinary metabolite tracking in diabetic conditions

We describe the advantages and diagnostic/prognostic significance of low-field, near-portable benchtop NMR spectrometers for the multicomponent metabolomics analysis of targeted and untargeted urinary biomarkers (≥15) in type 2 diabetes patients. Implementation of these facilities at ‘point-of-care’ clinical sites may yield valuable advantages for the sequential monitoring of diabetic and prediabetic individuals.

A comparison of non-uniform sampling and model-based analysis of NMR spectra for reaction monitoring.

Nuclear magnetic resonance (NMR) spectroscopy is widely used for applications in the field of reaction and process monitoring. When complex reaction mixtures are studied, NMR spectra often suffer from low resolution and overlapping peaks, which places high demands on the method used to acquire or to analyse the NMR spectra. This work presents two NMR methods that help overcome these challenges: 2D non-uniform sampling (NUS) and a recently proposed model-based fitting approach for the analysis of 1D NMR spectra. We use the reaction of glycerol with acetic acid as it produces five reaction products that are all chemically similar and, hence, challenging to distinguish. The reaction was measured on a high-field 400 MHz NMR spectrometer with a 2D NUS-heteronuclear single quantum coherence (HSQC) and a conventional 1D 1 H NMR sequence. We show that comparable results can be obtained using both 2D and 1D methods, if the 2D volume integrals of the 2D NUS-HSQC NMR spectra are calibrated. Further, we monitor the same reaction on a low-field 43 MHz benchtop NMR spectrometer and analyse the acquired 1D 1 H NMR spectra with the model-based approach and with partial least-squares regression (PLS-R), both trained using a single, calibrated data set. Both methods achieve results that are in good quantitative agreement with the high-field data. However, the model-based method was found to be less sensitive to the training data set used than PLS-R and, hence, was more robust when the reaction conditions differed from that of the training data.

Application of benchtop low-field NMR spectrometers in the refining industry: A multivariate calibration approach for rapid characterization of crude oils.

High-field nuclear magnetic resonance (NMR) has proven to be a valuable tool to analyze petroleum products but has never acquired widespread acceptance in routine work in oil refinery due to the high cost. The advent of compact, reliable, and affordable cryogen-free low-field benchtop NMR spectrometers suggest a possible role of such instrument for a variety of uses in refining spanning from routine lab work applications to online analysis. In this work, we report the development of a novel benchtop NMR application to estimate the API gravity, sulfur content, total acidity number (TAN), and distillation yields of crude petroleum from 60 MHz 1 H NMR spectra and partial least square (PLS) regression models. The results obtained on a dataset of over 170 crude oil samples and tested with external validation set show performances in terms of root mean square standard error of prediction (RMSEP) matching the analytical methods' ASTM precision. This novel benchtop NMR and multivariate analysis application can thus be used in typical refinery laboratories to provide within minutes and without physical distillation, reliable estimates of the most important properties usually measured on the crude petroleum during refining. The method proves to be a fast, cheaper alternative to the current analytical options providing readily available data for managing crude oil and has high potential to be further exploited for online application.

Shale rock core analysis using NMR: Effect of bitumen and water content

Hydrocarbon production from unconventional shale reservoirs has gained increasing worldwide focus, spurred largely by improvements in production techniques. Nuclear magnetic resonance (NMR) is increasingly being explored as a means of characterizing such shale rock. Compared to conventional sandstone and carbonate rocks, shales present a much lower porosity and permeability with NMR signal arising from both producible hydrocarbon fluid content as well as semi-solid organic solids and bitumen. Interpretation of the resultant NMR signal from shales is consequently comparatively more complex. To this end we apply combined NMR free induction decay (FID) and Carr-Purcell-Meilboom-Gill (CPMG) measurements and interpret the spliced data using a combined Gaussian and exponential inversion method. This was applied to a range of shale samples with variable moisture content in an attempt to assess the accuracy of such an approach to delineate the inherent predominantly bitumen signal from that of the added water. The analysis was performed at a range of frequencies (20, 40 and 60 MHz), which are applicable to more widely accessible bench-top NMR spectrometers. Consistently, the Gaussian component of the resultant T2*|T2 distribution was found to be independent of moisture content, scaling rather with the total organic content of the respective shale cores. In contrast, the exponential component of the resultant T2*|T2 distribution was found to scale linearly with the moisture content of the cores.

Quantitative analysis using external standards with a benchtop NMR spectrometer

This paper investigates the use of benchtop NMR spectrometers for quantitative analysis with external standards. Specifically, it focuses on the measurement of aqueous samples with analyte concentrations ranging from 30 mM to 1.7 M and electrical conductivity of up to 84mScm-1 using a 43 MHz instrument. It is demonstrated that measurements using the PULCON method cannot achieve an average error in quantification of <4% with the benchtop NMR tested here unless the standard and analyte are very similar. Our analysis indicates that this comparatively large error arises from the fixed tuning and matching of the benchtop spectrometer. We confirm that for moderately dilute samples (less than 0.2 M), the integral area of the solvent peak is suitable for use as an internal standard to mitigate this error. Furthermore, a round robin study demonstrates that the second major source of uncertainty in these measurements arises from the manual processing of the spectra by different analysts. Here we propose heuristics for manual baseline and phase correction to reduce this analyst-dependent error to about 3 %. We also demonstrate that semi-automated quantification using qGSD is able to achieve similar accuracy of integration, but with reduced sensitivity to the processing of the operator.

Feasibility of precise and reliable glucose quantification in human whole blood samples by 1 tesla benchtop NMR.

The standard procedure for blood glucose measurements is enzymatic testing. This method is cheap, but requires small samples of open blood with direct contact to the test medium. In principle, NMR provides non-contact analysis of body fluids, but high-field spectrometers are expensive and cannot be easily utilized under clinical conditions. Low-field NMR systems with permanent magnets are becoming increasingly smaller and more affordable. The studies presented here aim at exploring the capabilities of low-field NMR for measuring glucose concentrations in whole blood. For this purpose, a modern 1 T benchtop NMR spectrometer was used. Challenges arise from broad spectral lines, the glucose peak locations close to the water signal, low SNR and the interference with signals from other blood components. Whole blood as a sample comprises even more boundary conditions: crucial for reliable results are avoiding the separation of plasma and cells by gravitation and reliable reference values. First, the accuracy of glucose levels measured by NMR was tested using aqueous glucose solutions and commercially available bovine plasma. Then, 117 blood samples from oral glucose tolerance testing were measured with minimal preparation by simple pulse-acquire NMR experiments. The analysis itself is the key to achieve high precision, so several approaches were investigated: peak integration, orthogonal projection to latent structure analysis and support vector machine regression. Correlations between results from the NMR spectra and the routine laboratory automated analyzer revealed an RMSE of 7.90 mg/dL for the best model. 91.5% of the model output lies within the limits of the German Medical Association guidelines, which require the glucose measurement to be within 11% of the reference method. It is concluded that spectral quantification of glucose in whole blood samples by high-quality NMR spectrometers operating at 1 T is feasible with sufficient accuracy.

Incorporation of Benchtop NMR Spectrometer into the Organic Chemistry Laboratory: Analysis of an Unknown Liquid

Nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique in the organic chemistry laboratory for elucidation of molecular structure. Miniaturization of NMR technology has attracted attention and acceptance due to a considerable reduction in the cost to acquire and maintain the instrument. The advent of low-field, low-cost, and low-maintenance tabletop NMR technology has provided academic institutions with limited resources the option of hands-on NMR experimentation for undergraduates. The application of the tabletop NMR instrument in the organic chemistry laboratory to analyze an unknown liquid, which can be an ester, an aldehyde, an alcohol, or a ketone, together with infrared (IR) spectroscopy and classic chemical color tests, is herein described.