Search

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g−1. Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P(13C) = 25% within 8 min, through the combination of 1H spin diffusion and 1H → 13C cross polarization. Solutions of 13C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances., Hyperpolarization by dissolution dynamic nuclear polarization has brought highly sensitive magnetic resonance to reality but there still remains severe limitations. Here the authors show an approach relying on the generation of hyperpolarizing polymers that bear a dual function.

NMR based analysis of metabolite mixture provides crucial information on biological systems but mostly rely on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of 1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution Dynamic Nuclear Polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables 13C NMR based analysis of metabolites at natural-abundance. We have recently demonstrated the successful introduction of d-DNP into a full untargeted metabolomics workflow applied to the study of plant metabolism. Here we describe the systematic optimization of d-DNP experimental settings for experiments at natural 13C abundance, and show how the resolution, sensitivity, and ultimately the number of detectable signals improve as a result. We have systematically optimized the parameters involved (in a semi-automated prototype d-DNP system, from sample preparation to signal detection, aiming at providing an optimization guide for potential users of such system who may not be experts in instrumental development). The optimization procedure makes it possible to detect previously inaccessible protonated-13C signals of metabolites at natural abundance with at least 4 times improved line shape and a high repeatability compared to a previously reported d-DNP enhanced untargeted metabolomic study. This extends the application scope of hyperpolarized 13C NMR at natural abundance and paves the way to a more general use of DNP-hyperpolarised NMR in metabolomics studies.

We have recently demonstrated the use of contactless radiofrequency pulse sequences under dissolution-dynamic nuclear polarization conditions as an attractive way of transferring polarization from sensitive 1H spins to insensitive 13C spins with low peak radiofrequency pulse powers and energies via a reservoir of dipolar order. However, many factors remain to be investigated and optimized to enable the full potential of this polarization transfer process. We demonstrate herein the optimization of several key factors by: (i) implementing more efficient shaped radiofrequency pulses; (ii) adapting 13C spin labelling; and (iii) avoiding methyl group relaxation sinks. Experimental demonstrations are presented for the case of [1-13C]sodium acetate and other relevant molecular candidates. By employing the range of approaches set out above, polarization transfer using the dipolar order mediated cross-polarization radiofrequency pulse sequence is improved by factors approaching ∼1.65 compared with previous results. Dipolar order mediated 1H→13C polarization transfer efficiencies reaching ∼76% were achieved using significantly reduced peak radiofrequency pulse powers relative to the performance of highly sophisticated state-of-the-art cross-polarization methods, indicating 13C nuclear spin polarization levels on the order of ∼32.1% after 10 minutes of 1H DNP. The approach does not require extensive pulse sequence optimization procedures and can easily accommodate high concentrations of 13C-labelled molecules.

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of 1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables 13C NMR-based analysis of metabolites at natural abundance. We have recently demonstrated the successful introduction of d-DNP into a full untargeted metabolomics workflow applied to the study of plant metabolism. Here we describe the systematic optimization of d-DNP experimental settings for experiments at natural 13C abundance and show how the resolution, sensitivity, and ultimately the number of detectable signals improve as a result. We have systematically optimized the parameters involved (in a semi-automated prototype d-DNP system, from sample preparation to signal detection, aiming at providing an optimization guide for potential users of such a system, who may not be experts in instrumental development). The optimization procedure makes it possible to detect previously inaccessible protonated 13C signals of metabolites at natural abundance with at least 4 times improved line shape and a high repeatability compared to a previously reported d-DNP-enhanced untargeted metabolomic study. This extends the application scope of hyperpolarized 13C NMR at natural abundance and paves the way to a more general use of DNP-hyperpolarized NMR in metabolomics studies.

We have recently demonstrated the use of contactless radiofrequency pulse sequences under dissolution-dynamic nuclear polarization conditions as an attractive way of transferring polarization from sensitive 1H spins to insensitive 13C spins with low peak radiofrequency pulse powers and energies via a reservoir of dipolar order. However, many factors remain to be investigated and optimized to enable the full potential of this polarization transfer process. We demonstrate herein the optimization of several key factors by: (i) implementing more efficient shaped radiofrequency pulses; (ii) adapting 13C spin labelling; and (iii) avoiding methyl group relaxation sinks. Experimental demonstrations are presented for the case of [1-13C]sodium acetate and other relevant molecular candidates. By employing the range of approaches set out above, polarization transfer using the dipolar order mediated cross-polarization radiofrequency pulse sequence is improved by factors approaching ∼1.65 compared with previous results. Dipolar order mediated 1H→13C polarization transfer efficiencies reaching ∼76% were achieved using significantly reduced peak radiofrequency pulse powers relative to the performance of highly sophisticated state-of-the-art cross-polarization methods, indicating 13C nuclear spin polarization levels on the order of ∼32.1% after 10 minutes of 1H DNP. The approach does not require extensive pulse sequence optimization procedures and can easily accommodate high concentrations of 13C-labelled molecules.

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has brought highly sensitive magnetic resonance to reality and has triggered the development of a plethora of promising applications in spectroscopy and imaging. Unfortunately, some severe limitations still restrain its widespread use, amongst which the experimental complexity, the need for trained personnel, and excessive prices. Broad democratization of dDNP would require remote preparation of hyperpolarized samples in dedicated facilities and transport over long distances to the point of use. We have recently pioneered a new concept in which transport over hours was enabled by formulation of 13C-labelled molecules into micro-crystallites. However, the proposed methods lacked both versatility and biocompatibility. Here, we propose a new approach relying on a new generation of hyperpolarizing polymers (HYPOPs), extremely easy to synthesize, and that bear a dual function. Arbitrary solutions, easily impregnated into these radical-containing porous HYPOPs, can be hyperpolarized within 20 min with a polarization level exceeding P(13C) > 25% in the solid state, and further stored for hours in view of transport to a remote point of use.

Metabolomics plays a pivotal role in systems biology, and NMR is a central tool with high precision and exceptional resolution of chemical information. Most NMR metabolomic studies are based on 1H 1D spectroscopy, severely limited by peak overlap. 13C NMR benefits from a larger signal dispersion but is barely used in metabolomics due to ca. 6000-fold lower sensitivity. We introduce a new approach, based on hyperpolarized 13C NMR at natural abundance, that circumvents this limitation. A new untargeted NMR-based metabolomic workflow based on dissolution dynamic nuclear polarization (d-DNP) for the first time enabled hyperpolarized natural abundance 13C metabolomics. Statistical analysis of resulting hyperpolarized 13C data distinguishes two groups of plant (tomato) extracts and highlights biomarkers, in full agreement with previous results on the same biological model. We also optimize parameters of the semiautomated d-DNP system suitable for high-throughput studies.

International audience ; : In deuterated molecules such as [1-13C]pyruvate-d3, the nuclear spin polarization of 13C nuclei can be enhanced by combining Hartmann-Hahn Cross Polarization (CP) at low temperatures (1.2 K) with Dissolution Dynamic Nuclear Polarization (D-DNP). The polarization is transferred from remote solvent protons to the 13C spins of interest. This allows one not only to slightly reduce build-up times but also to increase polarization levels and extend the lifetimes T1(13C) of the enhanced 13C polarization during and after transfer from the polarizer to the NMR or MRI system. This extends timescales over which metabolic processes and chemical reactions can be monitored.

International audience; Dynamic Nuclear Polarization (DNP) is often achieved by the direct transfer of polarization from electrons to nuclei such as C-13, induced by microwave saturation of the wings of narrow EPR lines of radicals like trityl. In the indirect approach on the other hand, DNP is used to transfer the polarization from the electrons of radicals such as nitroxides that have broad EPR lines to nuclear spins I = H-1, followed by cross-polarization (CP) from I = H-1 to S = C-13 or other nuclei with low gyromagnetic ratios. This approach is particularly attractive for S = N-15, since direct DNP yields modest polarizations P(N-15) < 4% with build-up times that can be as long as tau DNP(N-15) > 2 h. In this paper, we show that CP from H-1 to N-15 at 1.2 K can yield P(N-15) = 25% with iota CP-DNP(N-15) = 10-15 min. After rapid dissolution and transfer to a solution-state NMR spectrometer, a polarization P(N-15) = 20% was observed at 300 K. The longitudinal relaxation times in solution can be as long as T-1(N-15) > 800 s in favorable cases.

International audience; The efficiency of dissolution dynamic nuclear polarization can be boosted by Hartmann-Hahn cross polarization at temperatures near 1.2 K. This enables high throughput of hyperpolarized solutions with substantial gains in buildup times and polarization levels. During dissolution and transport, the C-13 nuclear spin polarization P(C-13) merely decreases from 45 to 40%.

(EDT-TTF-CONH2)6[Re6Se8(CN)6], space group R, was prepared by electrocrystallization from the primary amide-functionalized ethylenedithiotetrathiafulvalene, EDT-TTF-CONH2 (E(1/2)1 = 0.49 V vs SCE in CH3CN), and the molecular cluster tetraanion, [Re6Se8(CN)6]4- (E(1/2) = 0.33 V vs SCE in CH3CN), equipped with hydrogen bond donor and hydrogen bond acceptor functionalities, respectively. Its Kagome topology is unprecedented for any TTF-based materials. The metallic state observed at room temperature has a strong two-dimensional character, in coherence with the Kagome lattice symmetry, and the presence of minute amounts of [Re6Se8(CN)6](3-)* identified by electron spin spectroscopy. A structural instability toward a distorted form of the Kagome topology of lesser symmetry is observed at ca. 180 K. The low-temperature structure is associated with a localized, electrically insulating electronic ground state and its magnetic susceptibility accounted for by a model of uniform chains of localized S = 1/2 spins in agreement with the 100 K triclinic crystal structure and band structure calculations. A sliding motion, within one out of the three (EDT-TTF-CONH2)2 dimers coupled to the [Re6Se8(CN6)(3-)*]/[Re6Se8(CN6)4-] proportion at any temperature, and the electronic ground state of the organic-inorganic hybrid material are analyzed on the basis of ESR, dc conductivity, 1H spin-lattice relaxation, and static susceptibility data which qualify a Mott localization in [EDT-TTF-CONH2]6[Re6Se8(CN)6]. The coupling between the metal-insulator transition and a structural transition allows for the lifting of a degeneracy due to the ternary axis in the high temperature, strongly correlated metallic phase which, in turn, leads to Heisenberg chains at low temperature.

An overview of the basic magnetic properties of vanadates which represent prototypes of frustrated two-dimensional S = 1/2 antiferromagnets on a square lattice is presented. It will be shown how information on the ground state sublattice magnetization, on the static uniform susceptibility and on the frustration driven lattice distortions can be achieved by means of NMR spectroscopy and magnetization measurements. The low-energy spin excitations, investigated by means of NMR and μSR relaxation measurements, will be analysed and the anomalous very-low-frequency dynamics, originating from the degeneracy of the ground state, discussed. Finally the effects of hydrostatic pressure on the degree of frustration of the vanadates will be addressed.

The design of high-temperature polymer fuel cells (PEMFCs), e.g. those expected for automotive applications, requires a deep understanding of the electrochemical reactions occurring in the device during operation. Operando electrochemical nuclear magnetic resonance microscopy can constitute a powerful investigation tool to this aim. At present, however, some strong technical limitations, like low sensitivity to less mobile protons, and the limited temperature range of analysis, have bound its use to case models based on perfluorinated membranes operating at high relative humidity and low temperature. By means of a suitable design of the experimental set-up and the use of a new 3D acquisition protocol, we proved the feasibility of electrochemical NMR microscopy on low-water containing polybenzimidazole-based devices, thus allowing full operando characterization of high-temperature PEMFCs, and also paving the way for applications to other electrochemical devices, such as batteries, sensors, supercapacitors, etc.

International audience; : Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion.

International audience; Cross polarization can provide significant enhancements with respect to direct polarization of low-gamma nuclei such as C-13. Substantial gains in sample throughput (shorter polarization times) can be achieved by exploiting shorter build-up times tau(DNP)(H-1) < tau(DNP)(C-13). To polarize protons rather than low-gamma nuclei, nitroxide radicals with broad ESR resonances such as TEMPO are more appropriate than Trityl and similar carbon-based radicals that have narrow lines. With TEMPO as polarizing agent, the main Dynamic Nuclear Polarization (DNP) mechanism is thermal mixing (TM). Cross polarization makes it possible to attain higher polarization levels at 2.2 K than one can obtain with direct DNP of low-gamma nuclei with TEMPO at 1.2 K, thus avoiding complex cryogenic technology.

The direct recording of the water presence in stone materials or in masonry provides information about their state of conservation and it can also indirectly reveal the effectiveness and durability of protection treatments or chemical interventions for rising damp reduction. Evaluating the humidity, i.e. the water content, of a building material is a problematic issue because the water is distributed in a large volume in different amounts. Usually these kinds of measures have been carried out with resistance/conductivity and thermographic systems, which are all affected by weaknesses and intrinsic restrictions. Thermographic investigations are affected by temperature differences and the evaporation–cooling effect. In the case of electric measures, the signal does not originate from the water present, but from the conductivity of the water itself, which is strictly connected to the presence of ion species that can modify it significantly. Moreover, interruptions, like air gaps or fractures, cancel the signal. For both methodologies the quantitative water evaluation is difficult. Although some minerals, like iron-based ones, could disturb the NMR measure, the signal is not influenced by the presence of most common soluble salts or pollutants in the solution (such as nitrates, chlorides or sulphates) and it is only generated by the number of water molecules present in the sensitive volume. In this paper the results, obtained in the laboratory with a portable NMR device, developed within the framework of the Eureka Project E!2214-MOUSE, are shown. The encouraging results obtained in this preliminary experiment, concern mainly the investigation of stone materials that have different porosimetric features and the calibration of the instrument under different working conditions. The experiments focused on the correlation between the content of water absorbed by capillarity and the NMR signal intensity obtained by this device. Different materials have been investigated, such as calcarenite and bricks. The experimental work will define a starting platform to successfully transfer the analytical procedure from the laboratory to in situ measurements.

The nuclear magnetic resonance (NMR) Surface scanner, which provides images of sample surfaces larger than the probe dimension. has been realized using a single-sided device. Although conditioned by distortion effects originated by convolution between the sensitive volume of the probe and the space structures to be imaged. the scanner is able to provide in images with Rood spatial resolution. The images obtained by the surface scanner can be made sensitive to relaxation parameters, magnetization or molecular self-diffusion: also. the dimension perpendicular to the sample surface can be scanned by varying the depth from which the probe detects the sample signal. It may scan Surfaces arbitrarily large and with some degree of curvature. This aspect, together with the noninvasive characteristic of the apparatus. indicates that the surface scanner could be used profitably in the field of cultural heritage. where it could provide NMR maps of frescos. paintings oil wood, marble artifacts, books and others. (C) 2006 Elsevier Inc. All rights reserved.

Muon spin resonance and ${}^{7}\mathrm{Li}$ NMR relaxation measurements in frustrated two-dimensional $S\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}\frac{1}{2}$ Heisenberg antiferromagnets on a square lattice are presented. It is found that, in both ${\mathrm{Li}}_{2}{\mathrm{VOSiO}}_{4}$ and ${\mathrm{Li}}_{2}{\mathrm{VOGeO}}_{4}$, spin dynamics at frequencies orders of magnitude below the Heisenberg exchange frequency are present. These dynamics are associated with the motions of walls separating coexisting collinear domains with a magnetic wave vector rotated by $90\ifmmode^\circ\else\textdegree\fi{}$.

Durante los últimos 25 años el gasto educativo público real en el Perú se ha mantenido relativamente constante, aunque con fluctuaciones relacionadas con el ciclo económico. Sin embargo, en un contexto de marcado crecimiento de la matrícula, esto ha implicado una caída significativa en el gasto por alumno, en particular, en la educación básica. Como parte de este proceso se observó un aumento del número de docentes y de personal administrativo - en particular a partir de 1985 - con una caída en los ingresos reales de los mismos. El gasto por alumno así como la variabilidad del gasto educativo en el Perú es similar al promedio latinoamericano. Sin embargo, el gasto es menos de un sexto del observado en países de la OECD. El gasto público en educación alcanzó el 2.8% del PBI en 1994. Estimaciones realizadas en base a encuestas de hogares muestran que las familias que matricularon a sus hijos en instituciones educativas públicas aportaron un 0.8%. Si además, se contabiliza el gasto de las familias en instituciones privadas, el gasto total de las familias llega a 1.9%. Así, si bien la educación pública, que en el caso de la educación básica constituye el 85% de la matrícula, es gratuita, las familias peruanas en conjunto gastan en educación -a través de aportaciones extraordinarias, cuotas de padres de familia, y gastos en materiales- 2/3 de lo que gasta el Estado. La sociedad peruana en conjunto gasta al menos 4.7% del PBI en educación. Finalmente, se encuentra que, la distribución del gasto educativo por alumno no es equitativa, siendo éste mayor en aquellos departamentos donde los indicadores de pobreza son menores.

International audience; Cross polarization from protons to quadrupolar Li-6 nuclei is combined with dynamic nuclear polarization of protons at 1.2 K and 6.7 T using TEMPOL as a polarizing agent followed by rapid dissolution. Compared to direct Li-6 DNP without cross-polarization, a higher nuclear spin polarization P(Li-6) can be obtained in a shorter time. A double resonance H-1-Li-6 probe was designed that is equipped for Longitudinally Detected Electron Spin Resonance.

In most applications of dissolution-DNP, the polarization of nuclei with low gyromagnetic ratios such as C-13 is enhanced directly by irradiating the ESR transitions of radicals with narrow ESR lines such as Trityl at low temperatures T = 1.2 K in polarizing fields B-0 C-13) in excess of 70% within 20 min. After rapid dissolution to room temperature, this is 122000 times larger than the Boltzmann polarization at 300 K and 6.7 T. (c) 2012 Elsevier B.V. All rights reserved.

The authors want to thank Dr. Jean-Nicolas Dumez for helpful discussions; Sven Sieber, Michael Schenkel, Rolf Hensel, Jacco van Beek, Ion Prisucaru, and Armin Purea for contributions to the system design and implementation; and Frank Engelke, Pietro Lendi, Klemens Kessler, Daniel Eckert, Daniel Guy Baumann, Dirk Wilhelm, Roberto Seydoux, Uwe Wagner, Cengiz Cetrefli, Tonio Gianotti, and Jorg Hinderer for contributions to the system specification. Some of the work in this article employed the SpinDynamica code for Mathematica, programmed by Malcolm H. Levitt, with contributions from Jyrki Rantaharju, Andreas Brinkmann, and Soumya Singha Roy, available at www.SpinDynamica.soton.ac.uk.; International audience; We present novel means to hyperpolarize deuterium nuclei in 13CD2 groups at cryogenic temperatures. The method is based on cross-polarization from 1H to 13C and does not require any radio-frequency fields applied to the deuterium nuclei. After rapid dissolution, a new class of long-lived spin states can be detected indirectly by 13C NMR in solution. These long-lived states result from a sextet-triplet imbalance (STI) that involves the two equivalent deuterons with spin I = 1. An STI has similar properties as a triplet-singlet imbalance that can occur in systems with two equivalent I = 12/ spins. Although the lifetimes T STI are shorter than T 1(Cz), they can exceed the life-time T 1(Dz) of deuterium Zeeman magnetization by a factor of more than 20.

International audience; Dissolution dynamic nuclear polarization (dDNP) has become a hyperpolarization method of choice for enhancing nuclear magnetic resonance (NMR) signals. Nuclear spins are polarized in solid frozen samples (in a so-called polarizer) that are subsequently dissolved and transferred to an NMR spectrometer for high sensitivity detection. One of the critical challenges of dDNP is that it requires both a fast transfer to limit nuclear spin relaxation losses as well as stability to guarantee high resolution (no bubbles nor turbulences). Here we describe the design, construction and performances of such a transfer and injection system, that features a 5 m/s speed and sub-Hz spectral resolution upon arrival at the detection spot. We demonstrate the use of such a system for inter-magnet distances of up to 10 m.