Nuclear magnetic resonance (NMR), conventionally detected in multi-tesla magnetic fields, is a powerful analytical tool for the determination of molecular identity, structure, and function. With the advent of prepolarization methods and alternative detection schemes using atomic magnetometers or superconducting quantum interference devices (SQUIDs), NMR in very low- (~earth's field), and even zero-field, has recently attracted considerable attention. Despite the use of SQUIDs or atomic magnetometers, low-field NMR typically suffers from low sensitivity compared to conventional high-field NMR. Here we demonstrate direct detection of zero-field NMR signals generated via parahydrogen induced polarization (PHIP), enabling high-resolution NMR without the use of any magnets. The sensitivity is sufficient to observe spectra exhibiting 13C-1H J-couplings in compounds with 13C in natural abundance in a single transient. The resulting spectra display distinct features that have straightforward interpretation and can be used for chemical fingerprinting.
We discuss a novel concept of a polarized nuclear target for accelerator fixed-target scattering experiments, which is based on parahydrogen induced polarization (PHIP). One may be able to reach a 33% free-proton polarization in the ethane molecule. The potential advantages of such a target include operation at zero magnetic field, fast ($\sim$100 Hz) polarization reversal, and operation with large intensity of an electron beam.
The sensitivity of NMR and MRI can be boosted via hyperpolarization of nuclear spins. However, current methods are costly, polarization is relatively low, or applicability is limited. Here, we report a new hyperpolarization method combining the low-cost, high polarization of hydrogenative parahydrogen-induced polarization (PHIP) with the flexibility of polarization transfer via proton exchange. The new method can be used to polarize various molecules, including alcohols, water, lactate, and pyruvate. On average, only $\approx$3 mM of a hyperpolarized transfer agent was sufficient to significan…
Development of the methods to exploit nuclear hyperpolarization and search for molecules whose nuclear spins can be efficiently hyperpolarized is an active area in nuclear magnetic resonance. Of particular interest are those molecules that have long nuclear relaxation times, making them to be suitable candidates as contrast agents in magnetic resonance imaging. In this work, we present a detailed study of SABRE SHEATH (Signal Amplification By Reversible Exchange in Shield Enabled Alignment Transfer to Heteronuclei) experiments of 15N,15N' azobenzene. In SABRE SHEATH experiments nuclear spins o…
Magnetic resonance imaging of $^{13}$C-labeled metabolites enhanced by parahydrogen-induced polarization (PHIP) can enable real-time monitoring of processes within the body. We introduce a robust, easily implementable technique for transferring parahydrogen-derived singlet order into 13C magnetization using adiabatic radio-frequency sweeps at $μ$T fields. We experimentally demonstrate the applicability of this technique to several molecules, including some molecules relevant for metabolic imaging, where we show significant improvements in the achievable polarization, in some cases reaching abo…
Robust nuclear hyperpolarization of small molecules through intermolecular transfer of parahydrogen-derived polarization
NVision Imaging Technologies GmbH（NVision成像技术有限公司）；Institute of Chemical Physics, Vilnius University（维尔纽斯大学化学物理研究所）；Institut für Theoretische Physik, Universität Ulm（乌尔姆大学理论物理研究所）；Center for Integrated Quantum Science and Technology (IQST)（集成量子科学与技术中心）；Dipartimento di Medicina, Scienze della Vita e dell’Ambiente, Università degli studi dell’Aquila（阿奎拉大学生命与环境科学医学系）；Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne（洛桑联邦理工学院化学科学与工程研究所）
Parahydrogen Cooling of Nuclear Spin Chains at Hypogeomagnetic Fields
International Tomography Center, SB RAS（俄罗斯科学院西伯利亚分院国际成像中心）；Novosibirsk State University（新西伯利亚国立大学）；Chimie Physique et Chimie du Vivant (CPCV, UMR 8228), Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université（巴黎高等师范学院化学系物理与生命化学实验室（CPCV，UMR 8228），PSL大学，索邦大学）；Johannes Gutenberg University, Institute of Physics（约翰内斯·古腾堡大学物理研究所）；Helmholtz Institute Mainz（美因茨亥姆霍兹研究所）；GSI Helmholtzzentrum für Schwerionenforschung GmbH（德国重离子研究中心亥姆霍兹有限公司）；Department of Chemistry, University of Miami（迈阿密大学化学系）；Department of Physics, University of Miami（迈阿密大学物理系）；Frost Institute for Chemistry and Molecular Science（弗罗斯特化学与分子科学研究所）
The field of magnetic resonance imaging with hyperpolarized contrast agents is rapidly expanding, and parahydrogen-induced polarization (PHIP) is emerging as an inexpensive and easy-to-implement method for generating the required hyperpolarized biomolecules. Hydrogenative PHIP delivers hyperpolarized proton spin order to a substrate via chemical addition of H2 in the spin-singlet state, but prior to imaging it is typically necessary to transfer the proton polarization to a heteronucleus (usually 13C) in the molecule. Adiabatic ultralow magnetic field manipulations can be used to induce the pol…
Nuclear Magnetic Resonance (NMR) is an intriguing quantum-mechanical effect that is used for daily life medical diagnostics and chemical analysis alike. Numerous advancements have contributed to the success of the technique, including hyperpolarized contrast agents that enables real-time imaging of metabolism in vivo. In physics, hyperpolarization has enabled an NMR RASER using a custom low-field setup and high-Q coils only recently. Expanding on this discovery, we report the finding of a RASER emitting 1H NMR signal continuously for more than 10 min at a high frequency of 600 MHz. Full chemic…
We show that high-resolution NMR can reach picomole sensitivity for micromolar concentrations of analyte by combining parahydrogen induced hyperpolarisation (PHIP)with a high-sensitivity transmission line micro-detector. The para-enriched hydrogen gas is introduced into solution by diffusion through a membrane integrated into a microfluidic chip. NMR microdetectors, operating with sample volumes of a few $μ$L or less, benefit from a favourable scaling of mass sensitivity. However, the small volumes make it very difficult to detect species present at less than millimolar concentrations in micro…
A theoretical approach is proposed for quantitative modeling of SABRE (Signal Amplification By Reversible Exchange) experiments performed at a high magnetic field of an NMR spectrometer. SABRE is a method, which exploits the spin order of parahydrogen (the H$_2$ molecule in its nuclear singlet state) for hyper-polarizing the spins of various substrates to enhance their NMR signals. An important feature of SABRE is that the substrate is not modified chemically: instead spin order transfer takes place in a transient complex with parahydrogen. In high-field SABRE experiments, such a transfer is a…
Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions in vivo. 1-13C-Pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the 13C spin at 121 μT magnetic field (\sim twiceEarth\apos s field) enables spin order transfer from parahydrogen to 13C magnetization of 1-13C-pyruvate. These so…
Zero- to ultralow-field nuclear magnetic resonance (ZULF NMR) is an alternative spectroscopic method to high-field NMR, in which samples are studied in the absence of a large magnetic field. Unfortunately, there is a large barrier to entry for many groups, because operating the optical magnetometers needed for signal detection requires some expertise in atomic physics and optics. Commercially available magnetometers offer a solution to this problem. Here we describe a simple ZULF NMR configuration employing commercial magnetometers, and demonstrate sufficient functionality to measure samples w…
The role of alignment-to-orientation conversion (AOC) in nuclear quadrupole resonance (NQR) is discussed. AOC is shown to be the mechanism responsible for the appearance of macroscopic orientation in a sample originally lacking any global polarization. Parallels are drawn between NQR and AOC in atomic physics.
We report detection of nuclear magnetic resonance (NMR) using an anisotropic magnetoresistive (AMR) sensor. A ``remote-detection'' arrangement was used, in which protons in flowing water were pre-polarized in the field of a superconducting NMR magnet, adiabatically inverted, and subsequently detected with an AMR sensor situated downstream from the magnet and the adiabatic inverter. AMR sensing is well suited for NMR detection in microfluidic ``lab-on-a-chip'' applications.
Nuclear inelastic scattering in conjunction with density functional theory (DFT) calculations has been applied for the identification of vibrational modes of the high-spin ferric and the high-spin ferrous iron-sulfur center of a rubredoxin-type protein from the thermophylic bacterium Pyrococcus abysii.
State-of-the-art magnetic resonance imaging uses hyperpolarized molecules to track metabolism in vivo, but large superconducting magnets are required, and the strong magnetic fields largely preclude measurement in the presence of conductive materials and magnify problems of magnetic susceptibility inhomogeneity. Operating at zero and low field circumvents these limitations, but until now has not been possible due to limited sensitivity. We show that zero- and low-field nuclear magnetic resonance can be used for probing two important metabolic reactions: the conversion of hyperpolarized fumarat…
Here we demonstrate that a term in the nuclear spin Hamiltonian, the antisymmetric \textit{J}-coupling, is fundamentally connected to molecular chirality. We propose and simulate a nuclear magnetic resonance (NMR) experiment to observe this interaction and differentiate between enantiomers without adding any additional chiral agent to the sample. The antisymmetric \textit{J}-coupling may be observed in the presence of molecular orientation by an external electric field. The opposite parity of the antisymmetric coupling tensor and the molecular electric dipole moment yields a sign change of the…
Density functional theory within the two-component quasi-relativistic zeroth-order regular approximation (ZORA) is used to predict parity violation shifts in 183W nuclear magnetic resonance shielding tensors of chiral, tetrahedrally bonded tungsten complexes of the form NWXYZ (X, Y, Z = H, F, Cl, Br or I). The calculations reveal that sub-mHz accuracy is required to detect such tiny effects in this class of compounds, and that parity violation effects are very sensitive to the choice of ligands.
While nuclear magnetic resonance diffusion experiments are widely used to resolve structures confining the diffusion process, it has been elusive whether they can exactly reveal these structures. This question is closely related to X-ray scattering and to Kac's "hear the drum" problem. Although the shape of the drum is not "hearable", we show that the confining boundary of closed pores can indeed be detected using modified Stejskal-Tanner magnetic field gradients that preserve the phase information and enable imaging of the average pore in a porous medium with a largely increased signal-to-noi…
The error-robust and short composite operations named ConCatenated Composite Pulses (CCCPs), developed as high-precision unitary operations in quantum information processing (QIP), are derived from composite pulses widely employed in nuclear magnetic resonance (NMR). CCCPs simultaneously compensate for two types of systematic errors, which was not possible with the known composite pulses in NMR. Our experiments demonstrate that CCCPs are powerful and versatile tools not only in QIP but also in NMR.
