A Portable Chip-Based Overhauser DNP Platform for Biomedical Liquid SampleAnalysis.

Heisenberg spin exchange effects of nitroxide radicals on Overhauser dynamic nuclear polarization in the low field limit at 1.5 mT

Overhauser Dynamic Nuclear Polarization for the Study of Hydration Dynamics, Explained

We designed and constructed a low-field setup for the study of nuclear magnetic resonance (NMR) and Overhauser dynamic nuclear polarization (DNP) in the shimmed stray magnetic field of a superconducting magnet with a variable magnetic field (0-8.5T). The experimental configuration is capable of exploring magnetic fields in the range of 0.5-30 mT by displacing the NMR/DNP probe from the superconducting magnet. Thanks to a constructed 3D gradient system comprising three coils wound on 3D-printed plastic holders, sufficient field homogeneity can be achieved (325 ppm in 0.7 ml volume, 98-fold homogeneity improvement) for strongly DNP-enhanced NMR signals or for measurements in concentrated solutions and porous media with broad NMR spectra. This setup allows us to study the magnetic field dependence of the Overhauser effect and underlying physical processes in aqueous solutions of radicals with an easy-to-built, low-cost, and low-power consumption magnet system. The design parameters of the gradient coils generating linear magnetic field gradients were optimized using the downhill simplex method in conjunction with magnetic field computations using Magpylib (a Python package). The NMR/DNP excitation chain allows for the use of a single broadband power amplifier to excite both nuclear and electronic spins and incorporates a custom-built NMR spectrometer for the generation and control of NMR and electron saturation pulses. In addition, we present a two-stage design for an NMR preamplifier, achieving a total gain of 68 dB, which combines a low-noise bipolar MMIC amplifier INA-02186 with an AD797 operational amplifier, enabling the detection of NMR signals over a frequency range of 30-1200kHz. DNP tests performed using a TEMPOL solution in water at a field strength of 4 mT demonstrate the efficacy of the assembled system for studying the DNP effect at low magnetic fields with high sensitivity.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for process monitoring. However, the quantitative analysis of highly diluted components or of components in small sample volumes is difficult with this analytical method due to its inherent lack of sensitivity. The hyperpolarization technique Overhauser dynamic nuclear polarization (ODNP) holds promise to solve this problem because it can provide strong signal enhancements. Furthermore, ODNP operates on short time scales and can therefore be used on flowing samples. Despite these advantages, to our knowledge, ODNP has never been applied for quantitative analysis of mixtures-probably because NMR signal enhancements by ODNP can vary greatly for different molecules, making quantitative analysis of mixtures difficult. We demonstrated that this problem can be solved by a robust calibration: three binary mixtures were studied as test cases in a wide range of concentrations by ODNP-enhanced H and C NMR spectroscopy in continuous-flow experiments with a benchtop NMR spectrometer using a new tailored calibration procedure. We show that quantitative analysis with ODNP-enhanced NMR spectroscopy is possible even under these challenging conditions.

High-field nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique for identification and characterization of chemicals and biomolecular structures. In the vast majority of NMR experiments, nuclear spin polarization arises from thermalization in multi-Tesla magnetic fields produced by superconducting magnets. In contrast, NMR instruments operating at low magnetic fields are emerging as a compact, inexpensive, and highly accessible alternative but suffer from low thermal polarization at a low field strength and consequently a low signal. However, certain hyperpolarization techniques create high polarization levels on target molecules independent of magnetic fields, giving low-field NMR a significant sensitivity boost. In this study, SABRE (Signal Amplification By Reversible Exchange) was combined with high homogeneity electromagnets operating at mT fields, enabling high resolution 1H, 13C, 15N, and 19F spectra to be detected with a single scan at magnetic fields between 1 mT and 10 mT. Chemical specificity is attained at mT magnetic fields with complex, highly resolved spectra. Most spectra are in the strong coupling regime where J-couplings are on the order of chemical shift differences. The spectra and the hyperpolarization spin dynamics are simulated with SPINACH. The simulations start from the parahydrogen singlet in the bound complex and include both chemical exchange and spin evolution at these mT fields. The simulations qualitatively match the experimental spectra and are used to identify the spin order terms formed during mT SABRE. The combination of low field NMR instruments with SABRE polarization results in sensitive measurements, even for rare spins with low gyromagnetic ratios at low magnetic fields.

Overhauser dynamic nuclear polarization (ODNP) is investigated at a moderately low field (1.2 T) for natural abundance 13C NMR of small molecules in solution state at room temperature. It is shown that ODNP transferred from 1H to 13C by NMR coherence transfer is in general significantly more efficient than direct ODNP of 13C. Compared to direct 13C ODNP, we demonstrate over 4-fold higher 13C sensitivity (signal-to-noise ratio, SNR), achieved in one-eighth of the measurement time by transferred ODNP (t-ODNP). Compared to the 13C signal arising from Boltzmann equilibrium in a fixed measurement time, this is equivalent to about 1500-fold enhancement of 13C signal by t-ODNP, as against a direct 13C ODNP signal enhancement of about 45-fold, both at a moderate ESR saturation factor of about 0.25. This owes in part to the short polarization times characteristic of 1H. Typically, t-ODNP reflects the essentially uniform ODNP enhancements of all protons in a molecule. Although the purpose of this work is to establish the superiority of t-ODNP vis-à-vis direct 13C ODNP, a comparison is also made of the SNR in t-ODNP experiments with standard high resolution NMR as well. Finally, the potential of t-ODNP experiments for 2D heteronuclear correlation spectroscopy of small molecules is demonstrated in 2D 1H-13C HETCOR experiments at natural abundance, with decoupling in both dimensions.

Event Abstract Back to Event Low-field NMR with magnetoresistive mixed sensors Natalia Sergeeva-Chollet1*, Hadrien Dyvorne1, Hedwige Polovy1, Myriam Pannetier-Lecoeur1 and Claude Fermon1 1 CEA, France Magnetoresistive sensors sensitivity has grown rapidly since the discovery of the Giant magnetoresistance effect (GMR). These sensors being field sensors, their sensitivity is independent of the size. For that reason, they have rapidly replaced coils in read heads. When coupled to a Giant Magnetoresistive (GMR) sensor, a superconducting loop containing a constriction can be an ultra sensitive magnetometer [1]. It has thermal noise levels of few fT/sqrt(Hz), comparable to LT- SQUID noise. These mixed sensors could be used for the detection of the biomagnetic signals like neuronal signature [2]. Furthermore, these devices are good candidates for low field Nuclear Magnetic Resonance (NMR) detection and Magnetic Resonance Imaging (MRI) especially at low and ultra low fields. They are very robust and accept strong RF pulses with a very short recovery time compared to tuned RF coils, which allow measurements of broad signals. We will show the results on NMR signal detection and first-MRI at low field without pre-polarization with such sensors. Finally, the perspectives of low-field MRI based on mixed sensors combined with neural signal detection (MEG) will be presented.

High-resolution Overhauser dynamic nuclear polarization enhanced proton NMR spectroscopy at low magnetic fields

Polymer-based Glass composite cylindrical structures consisting of multi-layered configuration for special applications were tested with low magnetic field nuclear magnetic resonance (NMR) technique. Relaxation times of chemical species at the interface of adhesive bond were investigated. Studies indicated that the single-sided NMR inspection of such composite structures is a feasible non-destructive evaluation technique to study the adhesive bond interface properties. Results of single-sided inspection over cylindrical surface using low field NMR having magnetic field strength of 0.3 T (12.88 MHz RF frequency) indicated distinct signal intensity values for different constituent materials. Interfacial defects such as de-bond and voids were detectable through the multi-layers of the structure. Overlapping defects at multiple interfaces have no bearing on the signal as well as relaxation times of constituent materials.

Nuclear magnetic resonance (NMR) spectroscopy in portable, permanent magnet-based spectrometers is primarily limited to nuclei with higher gyromagnetic ratio, γ, such as 1H, 19F, and 31P due to the limited field strength achievable in these systems. Overhauser effect dynamic nuclear polarization (O-DNP), which transfers polarization from an unpaired electron to a nucleus by saturating an electron paramagnetic resonance transition with an oscillating radio frequency magnetic field, B1e, can increase the polarization of low γ nuclei by hundreds or even thousands, enabling detection in a portable system. We have investigated the potential for O-DNP to enhance signals using (4-amino-2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO hereafter) as a source of unpaired electrons in a homebuilt ultra-low field (ULF) O-DNP-NMR spectrometer. We have found, in general, that larger concentrations of TEMPO are required for effective O-DNP with low γ nuclei, which has a number of important effects. Spin exchange effects cause the EPR lines to overlap and ultimately merge at high concentrations of TEMPO, fundamentally increasing the maximum possible enhancement, while the electron–electron dipolar interaction reduces both longitudinal and transverse relaxation times for the electrons, dramatically increasing the required B1e strength. The relationship between TEMPO concentration, B1e magnitude and O-DNP enhancement is quantified, and strategies for achieving these fields are discussed.

Separate and detailed characterization of signal and noise at low resonance frequencies.

Halogen bonding is a subject of considerable interest owing to wide-ranging chemical, materials and biological applications. The motional dynamics of halogen-bonded complexes play a pivotal role in comprehending the nature of the halogen-bonding interaction. However, not many attempts appear to have been made to shed light on the dynamical characteristics of halogen-bonded species. For the first time, we demonstrate here that the combination of low-field NMR relaxometry and Overhauser dynamic nuclear polarization (ODNP) makes it possible to obtain a cogent picture of the motional dynamics of halogen-bonded species. We discuss here the advantages of this combined approach. Low-field relaxometry allows us to infer the hydrodynamic radius and rotational correlation time, whereas ODNP probes the molecular translational correlation times (involving the substrate as well as the organic radical) with high sensitivity at low field.

Overhauser dynamic nuclear polarization (ODNP) in solutions of various paramagnetic complexes has been studied for 60 years, but only in recent years has found applications of broad interest to biophysical and biomedical sciences, for the investigation of soft materials and biomolecules. Relatively few aplications are focused on the ODNP in petroleum dispersed systems (PDS) like oils, bitumen, their fractions and solutions. This work present a short review of the ODNP studies of PDS with aim to introduce the basic concepts and key values for the effective petroleum ODNP in low and high magnetic fields. Experimental results obtained in our Laboratory by using home-made spectrometer are included. The study can be used for designing ODNP spectrometers, proton precession magnetometers for geological and geophysical exploration, investigation of supramolecular organisation of PDS and their components.

In porous media MR studies, discriminating between oil and water presents a challenge because MR lifetimes are often similar and spectra overlap. Low saturations might suggest an experimental strategy of increasing the static field for increased sensitivity, but susceptibility effects are exacerbated at higher field. Overhauser dynamic nuclear polarization, effective at low static field, was employed with water and oil-soluble nitroxide to selectively enhance water and oil signals. We employ a home-built 2 MHz ceramic magnet to achieve selective enhancement of water and oil, in bulk, and in a rock core. For imaging, we employ a 705 kHz ceramic magnet with a 4 gauss/cm constant gradient configuration to image the hyperpolarized signal. A rock core flooding experiment was undertaken to highlight the advantages of Overhauser enhancement. A simple phase cycling technique may be employed to cancel the thermally polarized 1H signal to isolate the enhanced signal of interest.

Overhauser dynamic nuclear polarization (OE-DNP) is capable of enhancing solution 13C NMR signals of analytes by 1-2 orders of magnitude through spin polarization transfer from paramagnetic polarizing agents, usually nitroxide radicals, at magnetic fields relevant for high-resolution NMR spectroscopy (≳9 T). While some halogen atoms have been revealed to mediate OE-DNP on adjacent 13C, methods of promoting OE-DNP through halogen bond (XB) design were not well-understood. Here we investigate OE-DNP of selected halogenated compounds by tuning their XB strengths to the nitroxide radicals through molecular design. Up to 10-fold boosts in OE-DNP enhancements were achieved by increasing the analyte XB donor strength in selected iodinated and brominated derivatives. Furthermore, we observed strong correlation between OE-DNP performance and XB properties for compounds sharing similar XB binding sites. Our results suggest new possibilities for designing hyperpolarized probes and labels for biosensors and the study of biomolecular processes.