The Field-Cycling NMR technique involves altering the magnetic fields of the sample during an experiment. This versatile method enables various applications that require measurements at different magnetic fields, such as MRI contrast agent studies, protein dynamics, or material science investigations.
To accurately measure NMR parameters across a wide magnetic field range while maintaining high-resolution spectra, the concept of shuttling the sample in a high-field NMR spectrometer has appeared. This approach takes advantage of the high-magnetic field and wide magnetic field range available in stray fields of high-field spectrometers. The time required for sample shuttling determines the speed of field switching, resulting in a technique known as "High-Field Field-Cycling NMR."
Such sample shuttling entails several crucial parameters: shuttling time, sample stability, and compatibility.
Shuttling time refers to the duration comprising the travel time of the sample and the time required for it to equilibrate within the high-field magnet system. This time interval signifies the transition period from sample relaxation to data collection. To ensure accurate measurement of physical parameters, the measured time constant should exceed the shuttling time. While the shuttling time is significantly shorter than the measured parameters, one can achieve higher accuracy, as the magnitude will not decay during sample shuttling.
Given the rapid movement of the sample, stability becomes a critical factor. Shuttling stability impacts the quality of spectra directly. For instance, while acquiring a two-dimensional NMR spectrum, an NMR sample must shuttle at least a hundred times within a single experiment. Each scan or serial data collection must occur under identical conditions to prevent the impacts on the data acquisition by the sample movements.
The compatibility of the shuttle instrument is critical as it influences the preservation of the spectrometer's performance. The primary objective of sample shuttling in high-field NMR spectrometers is to collect field-dependent information while maintaining the performance of the high-field NMR spectrometers. Therefore, an optimal situation would be for the shuttle system to seamlessly integrate with commercial probeheads and NMR spectrometers without causing hardware impacts during sample shuttling.
This animation simulated how the NMR tube inserting in commercial NMR probe in little clearance.
However, this implementation in high-field NMR brought significant challenges in hardware design:
- Limited Material Selection due to the High-Magnetic Field Environment: Operating in magnetic fields ranging from ultra-low to high magnetic fields, such as 9 Tesla or even higher up to 20 Tesla, necessitates the non-magnetic metal for the installed rail. Additionally, the moving components must be non-metallic to prevent the generation of eddy currents in strong magnetic fields.
- Constrained Space in the Magnetic Bore of High-Field NMR Spectrometers: The bore size of a standard NMR spectrometer is only 54mm in diameter, providing a narrow and elongated cylinder as the working space within the magnet bore.
- Minimal Margin between the Sample Tube and the Probe Head: The margin between the 5mm sample tube and the 5mm liquid-state probe head is narrow, often around 0.1mm or less. As a result, precise shuttling movements are necessary to avoid collisions or impacts with the probe head.
- Limited Material Selection for High-Speed and Frequent Shuttling to Minimize Wear: Rapid sample shuttling requires materials that can withstand high levels of wear and tear. Moreover, these materials must not be metallic.
Overcoming these challenges is essential for high-speed and stable sample shuttling in high-field NMR spectrometers. It allows for improved data acquisition and enhanced experimental capabilities.
Comparison of exisiting shuttle devices
Hence, achieving rapid and stable sample shuttling in high-field NMR spectrometers poses significant challenges. In response, many laboratories have taken the initiative to develop their own sample shuttle instruments, aiming to enable field-dependent measurements.
It is important to note that the values presented in the following are extracted from the corresponding publications, ensuring transparency and accuracy in reporting the information. Compatibility is an important consideration, particularly regarding the system's ability to be installed on different commercial probeheads. In the following table, if a system is marked as "No" in the compatibility column, it indicates that it requires a specially designed custom-made probehead, limiting its compatibility with standard probeheads.
In addition, the motor-driven sample shuttle offers higher stability than pneumatic control sample shuttles due to the inherent instability of air compression. The motor-driven mechanism provides consistent and reliable movement, ensuring precise positioning and minimizing the potential for disruptions caused by fluctuating air pressure. This stability enhances the overall performance and accuracy of the sample shuttling process in high-field NMR spectrometers.
|Citation||Driving force||Shuttling time||Compatibility|
|S. Grosse (1999)||Motor||0.3s(tsh) in 62cm||No|
|A. Redfield (2003)||Pneumatic||0.1s(tsh) + 0.2~0.3s(teq) in 100cm||Yes|
|H. Stork (2008)||Motor||0.1s(tsh) in 24cm||No|
|T-h. Huang (2011)||Motor||0.1s(tsh) in 100cm||Yes|
|A. Redfield (2012)||Motor||0.25s(tsh) in 11T to 1T||Yes|
|F. Ferrage (2013)||Pneumatic||0.054s(tsh)+0.1s(teq) in 46cm||No|
|A. Kiryutin (2014)||Motor||0.3s(tsh)+non-identified(teq) in 90cm||No|
|T. Theis (2020)||Pneumatic||0.5(tsh up)/1s(tsh down) + 1s(teq) in about 60cm||Yes|
|F. Ellermann (2023)||Motor||0.5s(tsh) + 0.4s(teq) in 30cm||adapted on tabletop NMR|
Note: tsh: sample shuttling time; teq: equilibrate time
The High-Field Field-Cycler (HFFC) has been specifically designed to be installed in the narrow bore of a commercial shared NMR spectrometer. See more.
In conclusion, the comparison of various sample shuttle systems highlights notable advancements in the field of hardware development for sample shuttling in high-field NMR. Among the systems discussed, T-h. Huang (2011) stands out for offering the shortest shuttling time and the highest compatibility. Their novel design of a mechanical field-cycling instrument achieves a comparable shuttling time to pneumatic control systems while demonstrating a shorter equilibration period. The system's successful adaptation to a commercial 5mm cryo-probe further validates its stability and sensitivity.
Our groundbreaking device, the High-Field Field-Cycler (HFFC) based on the design of T-h. Huang (2011), further improves rapid sample shuttling, allowing the sample to shuttle a distance of up to 100cm in just 80ms, with an equilibration time of only less than 30ms. This efficient and stable shuttling ensures the collection of high-quality spectra while preserving the performance of high-field NMR spectrometers. With its exceptional compatibility, the HFFC seamlessly integrates with various high-field NMR spectrometers and a wide range of commercial probeheads. This versatility ensures its adaptability to different experimental setups.
For more detailed information about our HFFC device, please visit our products page.
- Chou, CY, Chu, M. Chang, CF, Huang, TH. (2011). A compact high-speed mechanical sample shuttle for field-dependent high-resolution solution NMR. J. Magn. Res, (214) 302-8. 10.1016/j.jmr.2011.12.001.
- A. Refield, Journal of Biomolecular NMR 52(2):159-77
- Chou, CY., Chu, M., Chang, CF. et al. J Biomol NMR (2016) 66: 187. doi:10.1007/s10858-016-0066-5
- Redfield AG. High-resolution NMR field-cycling device for full-range relaxation and structural studies of biopolymers on a shared commercial instrument. Journal of Biomolecular NMR. 2012 Feb;52(2):159-177. DOI: 10.1007/s10858-011-9594-1. PMID: 22200887.
- Roberts MF and Hedstrom L (2022). High Resolution 31P Field Cycling NMR Reveals Unsuspected Features of Enzyme-Substrate-Cofactor Dynamics. Front. Mol. Biosci. 9:865519.