NMR spectroscopy is an essential analytical tool in the chemical and structural characterization of organic, inorganic, and biological samples. Due to high capital and maintenance costs, operational complexity and large magnet sizes, high-field NMR application is typically limited to advanced NMR facilities and R&D departments. Recent advances in permanent rare-earth magnet technology have allowed the introduction of benchtop NMR spectrometers that employ small permanent homogeneous magnets operating at 1H NMR frequencies of up to 100 MHz. Since their emergence over a decade ago, these compact instruments provide molecular level information (chemical shift) at the ease of a laboratory benchtop, without the complicated magnet cooling systems or cryogens and maintenance requirements of their bulky high-field counterparts.
Benchtop instruments have made NMR spectroscopy more accessible to chemists and have opened new opportunities for the chemical industry. As this technology continues to evolve, benchtop NMR users will experience streamlined industrial workflows and accelerated innovation in Research and Development.
Background
The use of desktop relaxometers (time-domain instruments) with inhomogeneous fields in applications such as food analysis and materials testing goes back to over 40 years ago. In the past decade, there have been many attempts to evaluate various prototypes and replace the earlier generation, bigger size, low-field NMR spectrometers in industrial uses such as reaction monitoring and process control. Recent benchtop NMR instruments provide chemical shift information, with lineshapes comparable to that of high-resolution NMR spectrometers. Although, by definition, benchtop instruments are considered “low field”, due to their advanced technology, it is possible to transfer many “high field” NMR applications to the lab bench. Today, the use of these instruments has gone beyond the rapid chemical analysis and extends to high throughput process control, metabolomic studies, flow chemistry, organic synthesis monitoring, and drug development.
Why Benchtop NMR
Similar to their bigger brothers, benchtop NMR systems are inherently a nondestructive biophysical tool and offer both quantitative and qualitative data. The advanced shimming technologies deliver narrow lineshapes to resolve analytes with great precision and sensitivity. The high-end benchtop instruments offer multinuclear capabilities and can be tuned to different nuclei without changing probes, which is of great importance for food and pharma applications. These instruments can also be equipped with auto samplers, have pulsed field gradients to allow recording of advanced NMR experiments, and be coupled with databasing software to facilitate quick identification of samples. In addition, compact NMR offers on-site analysis capabilities, simpler design (compared to high-field NMR and Mass Spectrometry), less analysis time, and easier sample handling (compared to MS), while providing sufficient accuracy with much lower cost. Overall, compared to other analytical tools, a benchtop NMR presents a speedier, more robust technique for many applications.
Current Applications of Benchtop NMR
In many modern research facilities, chemical workflows require synthetic or medicinal chemists to perform most routine structure confirmation using NMR. The robustness of a desktop NMR system, coupled with intuitive software, allows many bench and synthetic chemists to take advantage of the information-rich NMR technique in their everyday analysis and data interpretation; without the need for complicated background knowledge of instrument operation. Moreover, using a benchtop NMR instrument for this type of routine work frees up instrument time from the bigger systems that can be used for more time-consuming, specialized analyses.
While the high cost of superconducting NMR magnets is a typical limiting factor that preclude their use by smaller labs and organizations, benchtop NMR is more affordable and accessible. It can provide a platform to routinely perform NMR experiments in-house and avoid outsourcing costs, as expensive equipment, specialized labs, and specialists are no longer needed.
Moreover, benchtop NMR can become a practical educational tool in academic settings. NMR Spectroscopy is amongst one of the most challenging techniques to comprehend or teach. Although many students may be able to master the physical principles on which the methods are based on, in many institutes undergraduate students lack the personal experience to operate NMR spectrometers, which are typically limited in number and dedicated to the research labs. Accessible benchtop NMR spectrometers are more affordable for educational institutes and can help undergraduates get hands-on experience on this valuable analytical tool. In addition, the ability to rapidly record NMR spectra as part of the standard laboratory practice enhances the students’ appreciation of the technique and lifts the shroud of mystery and complexity surrounding it in the eyes of the young scientists.
Emerging Fields and Applications
Although benchtop NMR cannot fully replace a high-field NMR spectrometer, there are numerous emerging applications where benchtop NMR can be employed to streamline analytical workflows and enhance daily efficiency.
The portability of benchtop instruments has opened new possibilities in quality control and material testing when immediate results are crucial. An intriguing application is at the forensic labs and police departments for evaluating seized illicit drug samples and providing highly reliable, on the spot results. The tests can truly be performed “in the field”, without the need to wait days for the results from the specialized labs. This helps to build credibility and allows the authorities to quickly decide whether further law enforcement is necessary, prior to holding the suspects in custody. This is particularly true for the newer type of synthetic, analog drugs that may not exist in the lists of known drugs. While their analysis with MS would require standards that are difficult to obtain in a short time, with NMR the characteristic groups of the base drug can be identified rapidly.
A rising field since the availability of benchtop continuous flow NMR systems is flow chemistry, which by itself can revolutionize a broad range of industrial and academic applications such as drug development, reaction monitoring, and kinetics studies. These flow NMR systems allow continuous chemistry to be performed in a way that has not been achievable by conventional techniques. Transferring chemical reactions to a unique flow cell and variable temperature probe enables the chemists to closely monitor the reaction vessels and control the reaction progress and end-products in real-time. This will significantly reduce time, effort, and reagent volume, and increase yields of the reactions. The NMR instrument can literally be brought into the fume hood, instead of the other way round, thus reducing the complexity of the setup and eliminating potential compromises that may have been needed otherwise.
Another potential widespread application of the miniaturization of NMR is the use of NMR spectrometers to serve as chemical sensors in the medical field. The capability to detect metabolites in very low concentrations and short timescales, may enable future evaluation of the biomarkers in intact body fluids, such as urine or saliva, from within a patients’ home, by following exact protocols to expedite disease diagnosis.
NMR provides unprecedented levels of molecular and structural information that other analytical techniques cannot deliver. The use of big superconducting magnets can never be fully replaced and will always be in the forefront when it comes to pushing the boundaries in materials science, drug development, structural biology, and origin of many protein related diseases. Therefore, high field NMR magnets will continue to grow bigger and stronger. Meanwhile, benchtop NMR is an affordable capital cost with no additional maintenance charges. It provides a great complementary tool in R&D settings for pre-screening and flagging samples that require further characterization or assessment. Compact NMR can become a valuable educational tool in academic settings, and a great alternative for smaller labs to save time, money, and space for many routine applications. It is obvious that the applications of this technique will only continue to expand and develop further. In order to fully achieve its potential, we at ACD/Labs are working closely with benchtop NMR suppliers to bring the latest software applications and solutions to benchtop users. In addition, considering the ongoing innovations in electronics, field strength, and software, it is expected that smaller NMR versions will become more and more popular in the laboratory of the future, leading to an overall growth in the NMR market.