Category Archives: Instrumentation

Creating a clinical platform for carbon‐13 studies using the sodium‐23 and proton resonances #DNPNMR

Grist, James T., Esben S.S. Hansen, Juan D. Sánchez‐Heredia, Mary A. McLean, Rasmus Tougaard, Frank Riemer, Rolf F. Schulte, et al. “Creating a Clinical Platform for Carbon‐13 Studies Using the Sodium‐23 and Proton Resonances.” Magnetic Resonance in Medicine, March 13, 2020, mrm.28238.

https://doi.org/10.1002/mrm.28238

Purpose: Calibration of hyperpolarized 13C-MRI is limited by the low signal from endogenous carbon-containing molecules and consequently requires 13C-enriched external phantoms. This study investigated the feasibility of using either 23Na-MRI or 1H-MRI to calibrate the 13C excitation.

Methods: Commercial 13C-coils were used to estimate the transmit gain and center frequency for 13C and 23Na resonances. Simulations of the transmit B1 profile of a Helmholtz loop were performed. Noise correlation was measured for both nuclei. A retrospective analysis of human data assessing the use of the 1H resonance to predict [1-13C]pyruvate center frequency was also performed. In vivo experiments were undertaken in the lower limbs of 6 pigs following injection of hyperpolarized 13C-pyruvate.

Results: The difference in center frequencies and transmit gain between tissue 23Na and [1-13C]pyruvate was reproducible, with a mean scale factor of 1.05179 ± 0.00001 and 10.4 ± 0.2 dB, respectively. Utilizing the 1H water peak, it was possible to retrospectively predict the 13C-pyruvate center frequency with a standard deviation of only 11 Hz sufficient for spectral–spatial excitation-based studies.

Conclusion: We demonstrate the feasibility of using the 23Na and 1H resonances to calibrate the 13C transmit B1 using commercially available 13C-coils. The method provides a simple approach for in vivo calibration and could improve clinical workflow.

Characterization of frequency-chirped dynamic nuclear polarization in rotating solids #DNPNMR

Judge, Patrick T., Erika L. Sesti, Nicholas Alaniva, Edward P. Saliba, Lauren E. Price, Chukun Gao, Thomas Halbritter, Snorri Th. Sigurdsson, George B. Kyei, and Alexander B. Barnes. “Characterization of Frequency-Chirped Dynamic Nuclear Polarization in Rotating Solids.” Journal of Magnetic Resonance 313 (April 2020): 106702.

https://doi.org/10.1016/j.jmr.2020.106702

Continuous wave (CW) dynamic nuclear polarization (DNP) is used with magic angle spinning (MAS) to enhance the typically poor sensitivity of nuclear magnetic resonance (NMR) by orders of magnitude. In a recent publication we show that further enhancement is obtained by using a frequency-agile gyrotron to chirp incident microwave frequency through the electron resonance frequency during DNP transfer. Here we characterize the effect of chirped MAS DNP by investigating the sweep time, sweep width, center-frequency, and electron Rabi frequency of the chirps. We show the advantages of chirped DNP with a tritylnitroxide biradical, and a lack of improvement with chirped DNP using AMUPol, a nitroxide biradical. Frequency-chirped DNP on a model system of urea in a cryoprotecting matrix yields an enhancement of 142, 21% greater than that obtained with CW DNP. We then go beyond this model system and apply chirped DNP to intact human cells. In human Jurkat cells, frequency-chirped DNP improves enhancement by 24% over CW DNP. The characterization of the chirped DNP effect reveals instrument limitations on sweep time and sweep width, promising even greater increases in sensitivity with further technology development. These improvements in gyrotron technology, frequency-agile methods, and incell applications are expected to play a significant role in the advancement of MAS DNP.

Electron Paramagnetic Resonance Instrumentation #DNPNMR

Instrumentation for DNP-NMR spectroscopy has many similar components to instrumentation for EPR spectroscopy. This is a comprehensive review of the current state-of-the-art in EPR instrumentation, covering all aspects from magnet technology, pulse generation, detection and resonator design.

Reijerse, Edward, and Anton Savitsky. “Electron Paramagnetic Resonance Instrumentation.” In EMagRes, edited by Robin K. Harris and Roderick L. Wasylishen, 187–206. Chichester, UK: John Wiley & Sons, Ltd, 2017.

https://doi.org/10.1002/9780470034590.emrstm1511

The article gives a general overview of instrumentation commonly used in electron paramagnetic resonance. It includes magnet systems, microwave bridge configurations, and sample cryostats. A special focus has been placed on the discussion of various resonator and sample probe designs used in CW as well as pulsed EPR. Specialized EPR applications such as very high frequency EPR, electrochemistry, stopped flow, and the application to volume limited samples are briefly discussed.

Prediction of flow effects in quantitative NMR measurements

Friebel, Anne, Thomas Specht, Erik von Harbou, Kerstin Münnemann, and Hans Hasse. “Prediction of Flow Effects in Quantitative NMR Measurements.” Journal of Magnetic Resonance 312 (March 2020): 106683.

https://doi.org/10.1016/j.jmr.2020.106683

A method for the prediction of the magnetization in flow NMR experiments is presented, which can be applied to mixtures. It enables a quantitative evaluation of NMR spectra of flowing liquid samples even in cases in which the magnetization is limited by the flow. A transport model of the nuclei’s magnetization, which is based on the Bloch-equations, is introduced into a computational fluid dynamics (CFD) code. This code predicts the velocity field and relative magnetization of different nuclei for any chosen flow cell geometry, fluid and flow rate. The prediction of relative magnetization is used to correct the observed reduction of signal intensity caused by incomplete premagnetization in fast flowing liquids. By means of the model, quantitative NMR measurements at high flow rates are possible. The method is predictive and enables calculating correction factors for any flow cell design and operating condition based on simple static T1 time measurements. This makes time-consuming calibration measurements for assessing the influence of flow effects obsolete, which otherwise would have to be carried out for each studied condition. The new method is especially interesting for flow measurements with compact medium field NMR spectrometers, which have small premagnetization volumes. In the present work, experiments with three different flow cells in a medium field NMR spectrometer were carried out. Acetonitrile, water, and mixtures of these components were used as model fluids. The experimental results for the magnetization were compared to the predictions from the CFD model and good agreement was observed.

Millimeter-wave Sources for DNP-NMR #DNPNMR

Blank, Monica, and Kevin L Felch. “Millimeter-Wave Sources for DNP-NMR” 7 (2018): 12.

https://doi.org/10.1002/9780470034590.emrstm1582

Advances in both solid-state and vacuum-electron-based sources at frequencies greater than 200 GHz have been a key factor in the recent improvements in solid-state dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) instrumentation. The current state of the art in solid-state sources and vacuum-electron devices (VEDs), such as extended interaction oscillators (EIOs), extended interaction klystrons (EIKs), and gyrotrons for DNP applications are described. The key features and design aspects of gyrotrons, which are presently the most promising DNP sources for high-field NMR systems, are detailed. In addition, the current capabilities of high-performance DNP gyrotron sources are illustrated. The status of ongoing research efforts in DNP gyrotrons and future directions are discussed.

Pulse-Shaped Dynamic Nuclear Polarization under Magic-Angle Spinning #DNPNMR

Equbal, Asif, Kan Tagami, and Songi Han. “Pulse-Shaped Dynamic Nuclear Polarization under Magic-Angle Spinning.” The Journal of Physical Chemistry Letters 10, no. 24 (December 19, 2019): 7781–88.

https://doi.org/10.1021/acs.jpclett.9b03070

Dynamic nuclear polarization (DNP) under magic-angle spinning (MAS) is transforming the scope of solid-state NMR by enormous signal amplification through transfer of polarization from electron spins to nuclear spins. Contemporary MAS-DNP exclusively relies on monochromatic continuous-wave (CW) irradiation of the electron spin resonance. This limits control on electron spin dynamics, which renders the DNP process inefficient, especially at higher magnetic fields and non cryogenic temperatures. Pulse-shaped microwave irradiation of the electron spins is predicted to overcome these challenges but hitherto has never been implemented under MAS. Here, we debut pulse-shaped microwave irradiation using arbitrary-waveform generation (AWG) which allows controlled recruitment of a greater number of electron spins per unit time, favorable for MAS-DNP. Experiments and quantum mechanical simulations demonstrate that pulse-shaped DNP is superior to CW-DNP for mixed radical system, especially when the electron spin resonance is heterogeneously broadened and/or when its spin−lattice relaxation is fast compared to the MAS rotor period, opening new prospects for MAS-DNP.

Progress in low-field benchtop NMR spectroscopy in chemical and biochemical analysis

Grootveld, Martin, Benita Percival, Miles Gibson, Yasan Osman, Mark Edgar, Marco Molinari, Melissa L. Mather, Federico Casanova, and Philippe B. Wilson. “Progress in Low-Field Benchtop NMR Spectroscopy in Chemical and Biochemical Analysis.” Analytica Chimica Acta 1067 (August 2019): 11–30.

https://doi.org/10.1016/j.aca.2019.02.026

The employment of spectroscopically-resolved NMR techniques as analytical probes have previously been both prohibitively expensive and logistically challenging in view of the large sizes of high-field facilities. However, with recent advances in the miniaturisation of magnetic resonance technology, low-field, cryogen-free “benchtop” NMR instruments are seeing wider use. Indeed, these miniaturised spectrometers are utilised in areas ranging from food and agricultural analyses, through to human biofluid assays and disease monitoring. Therefore, it is both intrinsically timely and important to highlight current applications of this analytical strategy, and also provide an outlook for the future, where this approach may be applied to a wider range of analytical problems, both qualitatively and quantitatively. © 2019 Elsevier B.V. All rights reserved.

Shim-on-Chip Design for Microfluidic NMR Detectors

Active shims to achieve high-resolution spectra are crucial parts of the NMR instrumentation. Typically, shims are designed to produce a magnetic correction field corresponding to individual spherical harmonics. Other methods have been proposed (e.g. matrix shims) and the approach described in this article simplify uses flat ribbon cables.

Meerten, S. G. J. van, P. J. M. van Bentum, and A. P. M. Kentgens. “Shim-on-Chip Design for Microfluidic NMR Detectors.” Analytical Chemistry 90, no. 17 (September 4, 2018): 10134–38.

https://doi.org/10.1021/acs.analchem.8b02284

In this contribution we present a novel system for shimming capillary samples such as used in microuidic NMR probe heads. Due to the small sample size shimming microliter samples using regular shim coils is complicated. Here we demonstrate the use of a series of parallel wires placed perpendicular to B0 as a Shim-on-Chip shim system. This is achieved by placing a ribbon at cable horizontally over the NMR detector, in our case a stripline. The current through each wire of the ribbon cable can be controlled independently employing a 16 channel DAC. This makes for a simple, cheap and easy to construct alternative to regular shim systems. The Shim-on-Chip is, nevertheless, quite exible in creating a magnetic eld which matches the inhomogeneity of the magnet in 1 dimension. The capillary sample geometry is well suited for this type of shimming since its length (8mm) is much larger than its width (100 µm to 250 µm). With this Shim-on-Chip system we have reached linewidths of 2:2 Hz (at 50%) and 27 Hz (at 0:55%) on a 144MHz NMR spectrometer without any other room temperature shims. Unlike regular shims the Shim-on-Chip is located inside the NMR probe. It is always centered on the NMR sample, because of this the shims have an intuitive eect on the lineshape. Therefore the manual shimming is simpler when compared to a regular shim system, as it is dicult to position a microliter sample in the exact center of the shim coils. We furthermore demonstrate the use of a Shim-on-Chip method in a 400MHz Rapid-Melt DNP system. Decent linewidths were achieved even for a sample which is located o-center inside the NMR magnet.

High-Resolution Overhauser Dynamic Nuclear Polarization Enhanced Proton NMR Spectroscopy at Low Magnetic Fields #DNPNMR #Bridge12

Overhauser DNP spectroscopy at X-Band is mostly used to study hydration dynamics. However, using a hybrid magnet (permanent magnet in combination with sweep coils) with active shimming it is possible to record high-resolution NMR spectra with chemical shift resolution. This is an example of the research and development activities performed at Bridge12.

Keller, Timothy J., Alexander J. Laut, Jagadishwar Sirigiri, and Thorsten Maly. “High-Resolution Overhauser Dynamic Nuclear Polarization Enhanced Proton NMR Spectroscopy at Low Magnetic Fields.” Journal of Magnetic Resonance, March 2020, 106719. 

https://doi.org/10.1016/j.jmr.2020.106719.

Dynamic nuclear polarization (DNP) has gained large interest due to its ability to increase signal intensities in nuclear magnetic resonance (NMR) experiments by several orders of magnitude. Currently, DNP is typically used to enhance high-field, solid-state NMR experiments. However, the method is also capable of dramatically increasing the observed signal intensities in solution-state NMR spectroscopy. In this work, we demonstrate the application of Overhauser dynamic nuclear polarization (ODNP) spectroscopy at an NMR frequency of 14.5 MHz (0.35 T) to observe DNP-enhanced highresolution NMR spectra of small molecules in solutions. Using a compact hybrid magnet with integrated shim coils to improve the magnetic field homogeneity we are able to routinely obtain proton linewidths of less than 4 Hz and enhancement factors > 30. The excellent field resolution allows us to perform chemical-shift resolved ODNP experiments on ethyl crotonate to observe proton J-coupling. Furthermore, recording high-resolution ODNP-enhanced NMR spectra of ethylene glycol allows us to characterize the microwave induced sample heating in-situ, by measuring the separation of the OH and CH2 proton peaks.

Prediction of flow effects in quantitative NMR measurements #DNPNMR

Friebel, Anne, Thomas Specht, Erik von Harbou, Kerstin Münnemann, and Hans Hasse. “Prediction of Flow Effects in Quantitative NMR Measurements.” Journal of Magnetic Resonance 312 (March 2020): 106683.

https://doi.org/10.1016/j.jmr.2020.106683.

A method for the prediction of the magnetization in flow NMR experiments is presented, which can be applied to mixtures. It enables a quantitative evaluation of NMR spectra of flowing liquid samples even in cases in which the magnetization is limited by the flow. A transport model of the nuclei’s magnetization, which is based on the Bloch-equations, is introduced into a computational fluid dynamics (CFD) code. This code predicts the velocity field and relative magnetization of different nuclei for any chosen flow cell geometry, fluid and flow rate. The prediction of relative magnetization is used to correct the observed reduction of signal intensity caused by incomplete premagnetization in fast flowing liquids. By means of the model, quantitative NMR measurements at high flow rates are possible. The method is predictive and enables calculating correction factors for any flow cell design and operating condition based on simple static T1 time measurements. This makes time-consuming calibration measurements for assessing the influence of flow effects obsolete, which otherwise would have to be carried out for each studied condition. The new method is especially interesting for flow measurements with compact medium field NMR spectrometers, which have small premagnetization volumes. In the present work, experiments with three different flow cells in a medium field NMR spectrometer were carried out. Acetonitrile, water, and mixtures of these components were used as model fluids. The experimental results for the magnetization were compared to the predictions from the CFD model and good agreement was observed.

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