Exploring Applications of Time Domain Nuclear Magnetic Resonance
Nuclear magnetic resonance
Nuclear magnetic resonance (NMR) is a powerful analytical tool used in research to obtain detailed information about the structure, dynamics, reaction state, and chemical environment of molecules and in medicine to provide images of soft tissue.
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There are numerous distinct NMR methodologies all based on the principle that exposure to a magnetic field, causes nuclei to be elevated to a higher energy level, and this energy transfer is reversed on removal of the magnetic field. The diverse techniques are broadly categorised as spectroscopy, imaging or relaxometry.
NMR spectroscopy measures the radiofrequency of the energy released when the excited nuclei return to their base energy level. The high level of detail and spatial resolution provided by NMR spectroscopy revolutionised biological research by enabling characterisation of increasingly complex molecules. In particular, it was fundamental to the elucidation of the structure and function of a multitude of proteins, which in turn furthered the understanding and treatment of many disease processes. In the 1980's, the technique was extended to the medical profession in the form of magnetic resonance imaging (MRI), which allows in vivo investigation of soft tissues to inform diagnostic and treatment decisions.
NMR spectroscopy is a highly specialized technique and initially could only be performed by skilled operators and the determination of structure required an in-depth knowledge of chemistry and physics. With advances in technology providing fully automated instrumentation and the development of software to interpret data, only minimal training is now required. However, due to the expense and size of the sophisticated spectrometers required, NMR spectroscopy is not feasible for all applications.
The high cost and bulky nature of instrumentation for NMR spectroscopy and imaging stems from the requirement for high-field superconducting magnets to achieve chemical shift resolution. NMR relaxometry (also known as time domain NMR) can be performed without spectroscopy or imaging, and so can be conducted using smaller, less expensive low-field permanent magnets. Although this methodology sacrifices the power of atomic or spatial resolution, it has the advantages of being portable and cost-effective. For this reason, despite being less powerful time domain NMR is gaining in popularity. It allows NMR to be used in settings beyond the specialized NMR laboratory or imaging centre and is being employed in an ever-increasing range of applications.
Time domain NMR
Time domain NMR measures the time required for nuclei to return to equilibrium after excitation. It is widely recognized as a reliable, convenient, rapid analytical methodology that shows high reproducibility without the need for sample preparation and is non-destructive.
A variety of benchtop, compact time domain NMR spectrometers have been developed that can achieve 1H resonance frequencies of approximately 5–60 MHz (that is around one-to-two orders of magnitude lower than the conventional NMR spectrometers).
In addition to being more affordable and portable, time domain NMR spectrometers accommodate a much wider range of sample type, including semi-solid or liquid crystalline samples and heterogeneous samples. Consequently, there are many analytical tasks that can be adequately addressed without the need for high-end spectroscopy or imaging.
Having been over-shadowed for many years by tremendous advances in high-field spectroscopy and imaging, time domain NMR is making a come-back. The portability and affordability of this simple methodology afford a multitude of exciting new opportunities for NMR. Current applications of compact time domain NMR include quality testing in the petrochemical and food industries and diagnostic blood tests, eg, for insulin resistance.
Evaluating nanofluidity with NMR
One of the many new avenues of research in which time domain NMR has been explored is in the determination of nanofluidity in biological systems.
The fluidity of lipid-rich assemblies, such serum lipoproteins and cell membranes, is an important factor in determining their physical properties and biological functions1. It can vary according to hydrocarbon chain composition and in response to temperature changes. The extent of fluidity of the hydrocarbon chains within biological membranes is thought to be a key determinant of cell surface receptor function2. Similarly, it can dictate the rate at which cholesterol in the form of low-density lipoproteins is cleared from the blood3.
Time domain NMR is actually better suited to studying lipids in cell membranes that NMR spectroscopy since it does not rely on chemical shift resolution or narrow NMR resonances. Furthermore, the relaxation time constants provided by time domain NMR provide valuable information. Hydrocarbon chain fluidity has also been assessed using fluorescence electron spin resonance, but this is associated with concerns that the probe may interfere with nearby structures.
Using a Bruker mq40 minispec time domain benchtop NMR relaxometer with a permanent magnet, researchers studied a series of single-phase fatty acid oils4. They were able to correlate 1H spin−spin relaxation time constants (T2) obtained by time domain NMR with measures of fluidity obtained using a viscometer. The technique successfully resolved two to four T2 components in biologically relevant fatty acids. T2 values for each domain of the hydrocarbon chain exhibited positive linear correlations with fluidity.
The results from this study illustrate that time domain NMR using benchtop instrumentation achieves significant resolving power and is sensitive to differences in hydrocarbon chain structure and composition. There is consequently potential for time domain NMR to be used to monitor nanofluidity in other biological systems.
References
- Vance D and Vance J, Eds. (2008) Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier, Amsterdam.
- Nicolson G. The fluid mosaic model of membrane structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. Biochim. Biophys. Acta 2014;1838:1451−1466.
- Melchoir J, et al. LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis. J. Lipid Res.2013;54:2495−2503.
- Robinson MD and Cistola DP. Nanofluidity of Fatty Acid Hydrocarbon Chains As Monitored by Benchtop Time-Domain Nuclear Magnetic Resonance. Biochemistry 2014, 53, 7515−7522.
About Bruker
Bruker is market leader in analytical magnetic resonance instruments including NMR, EPR and preclinical magnetic resonance imaging (MRI). Bruker's product portfolio in the field of magnetic resonance includes NMR, preclinical MRI, EPR and Time-Domain (TD) NMR. In addition.Bruker delivers the world's most comprehensive range of research tools enabling life science, materials science, analytical chemistry, process control and clinical research. Bruker is also the leading superconductor magnet and ultra high field magnet manufacturer for NMR and MRI solutions.
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Last updated: Apr 3, 2018 at 12:02 PM
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