An automated system for fast transfer and injection of hyperpolarized solutions

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

Développements instrumentaux pour la polarisation dynamique nucléaire avec dissolution : générer, transférer et transporter des échantillons hyperpolarisés

Nuclear magnetic resonance (NMR) is a powerful analytical chemistry tool but, unfortunately, it often severely lacks sensitivity. One of the most efficient way to enhance the NMR signal is called dissolution dynamic nuclear polarization (dDNP). Here, a sample mixed with radicals is hyperpolarized in a liquid helium bath of a polarizer, through microwaves irradiation. Then, a hot pressurized solvent is flushed onto the frozen sample to rapidly melt and dissolve it. The dissolved sample is then transferred to an acquisition device, whether an NMR spectrometer or an MRI scanner. High enhancements of 4 or 5 orders of magnitude can be reached this way. Though a powerful method, dDNP still suffers from several instrumental drawbacks. First, the transfer speed of the hyperpolarized sample is often in the order of 10 s, which is not enough for observing fast relaxing nuclear spins. Second, important quantities of expensive liquid helium are required to cool down the sample, and most of the polarizers do not recycle helium. Finally, the relaxations in the liquid-state are in the order of a few seconds up to minutes at most, which implies that polarizers must be placed close to the acquisition device. This thesis aims at proposing instrumental solutions to the problems above. A fast liquid-driven transfer system is presented, with transfers as fast as 5 m.s-1. A new type of helium-recycling polarizer is described, along with a dedicated home-built dDNP probe. Finally, a system used to maintain and transport hyperpolarization over several hours is describedLa résonance magnétique nucléaire (RMN) est une méthode de pointe en chimie analytique mais qui, malheureusement, manque souvent cruellement de sensibilité. L’une des techniques les plus performantes pour augmenter le signal RMN est appelée la polarisation dynamique nucléaire avec dissolution (PDNd). Des micro-ondes sont appliquées sur un échantillon mélangé avec des radicaux et placé dans le bain d’hélium liquide d’un polariseur, afin d’atteindre un état d’hyperpolarisation. L’échantillon gelé est ensuite dissout rapidement dans un solvant surchauffé et transféré vers un spectromètre RMN ou un IRM. Des augmentations de signal de 4 à 5 ordres de grandeur peuvent ainsi être obtenus. Malgré ses avantages, la PDNd possède plusieurs limitations instrumentales. Tout d’abord, les transferts d’échantillons hyperpolarisés se font souvent en une dizaine de secondes, ce qui est trop lent pour observer des spins nucléaires à relaxation rapide. Ensuite, de grandes quantités couteuses d’hélium liquide sont nécessaires pour refroidir l’échantillon, et l’hélium n’est souvent pas recyclé. Enfin, les temps de relaxation des noyaux à l’état liquide varient en moyenne entre quelques secondes et quelques minutes, ce qui nécessite une courte distance entre le polariseur et l’instrument d’acquisition. Le but de cette thèse est de tenter de répondre à ces problématiques. Un système de transfert rapide est ainsi proposé, avec des transferts en 5 m.s-1. Un nouveau type de polariseur recyclant l’hélium est décrit ainsi que sa sonde dédiée. Finalement, un système permettant de maintenir et transporter l’hyperpolarisation sur plusieurs heures est décri

Practical dissolution dynamic nuclear polarization

This review article intends to provide insightful advice for dissolution-dynamic nuclear polarization in the form of a practical handbook. The goal is to aid research groups to effectively perform such experiments in their own laboratories. Previous review articles on this subject have covered a large number of useful topics including instrumentation, experimentation, theory, etc. The topics to be addressed here will include tips for sample preparation and for checking sample health; a checklist to correctly diagnose system faults and perform general maintenance; the necessary mechanical requirements regarding sample dissolution; and aids for accurate, fast and reliable polarization quantification. Herein, the challenges and limitations of each stage of a typical dissolutiondynamic nuclear polarization experiment are presented, with the focus being on how to quickly and simply overcome some of the limitations often encountered in the laboratory

Boosting Dissolution-Dynamic Nuclear Polarization by Multiple-Step Dipolar Order Mediated 1H->13C Cross-Polarization

Dissolution-dynamic nuclear polarization can be boosted by employing multiplecontact cross-polarization techniques to transfer polarization from 1H to 13C spins. The method is efficient and significantly reduces polarization build-up times, however, it involves high-power radiofrequency pulses in a superfluid helium environment which limit its implementation and applicability and prevent a significant scaling-up of the sample size. We propose to overcome this limitation by a stepwise transfer of polarization using a lowenergy and low-peak power radiofrequency pulse sequence where the 1H®13C polarization transfer is mediated by a dipolar spin order reservoir. An experimental demonstration is presented for [1-13C]sodium acetate. A solid-state 13C polarization of ~43.5% was achieved using this method with a build-up time constant of ~5.1 minutes, leading to a ~28.5% 13C polarization in the liquidstate after sample dissolution. The low-power multiple-step polarization transfer efficiency with respect to the most advanced and highest-power multiple-contact cross-polarization approach was found to be ~0.69.</p

Rapid and simple 13C-hyperpolarization by 1H dissolution dynamic nuclear polarization followed by an in-line magnetic field inversion

Dissolution dynamic nuclear polarization (dDNP) is a method of choice for preparing hyperpolarized 13C metabolites such as [1-13C]-pyruvate used for in vivo applications including the real-time monitoring of cancer cell metabolism in human patients. The approach consists of transferring the high polarization of electron spins to nuclear spins via microwave irradiation at low temperatures (1.0-1.5 K) and moderate magnetic fields (3.3-7 T). The solid sample is then dissolved and transferred to an NMR spectrometer or MRI scanner for detection in the liquid state. Common dDNP protocols use direct hyperpolarization of13C spins reaching polarizations of >50% in ~1-2 hours. Alternatively, 1H spins are polarized before transferring their polarization to 13C spins using cross-polarization (CP), reaching similar polarization levels as direct DNP in only ~20 min. However, it relies on more complex instrumentation, requiring highly skilled personnel. Here, we explore an alternative route using 1H dDNP followed by an inline adiabatic magnetic field inversion in the liquid state during the transfer. 1H polarizations of >70% in the solid-state are obtained in ~5-10 min. As the hyperpolarized sample travels from the dDNP polarizer to the NMR spectrometer, it goes through a field inversion chamber, which causes 1H→13C polarization transfer. This transfer is made possible by the J-coupling between the heteronuclei, which mixes the Zeeman states at zero-field and causes an anti-level crossing. We report liquid-state 13C polarization up to ~17% for [3-13C]-pyruvate and 13C-formate. The instrumentation needed to perform this experiment in addition to a conventional dDNP polarizer is simple and readily assembled

Practical dissolution dynamic nuclear polarization

This review article intends to provide insightful advice for dissolution-dynamic nuclear polarization in the form of a practical handbook. The goal is to aid research groups to effectively perform such experiments in their own laboratories. Previous review articles on this subject have covered a large number of useful topics including instrumentation, experimentation, theory, etc. The topics to be addressed here will include tips for sample preparation and for checking sample health; a checklist to correctly diagnose system faults and perform general maintenance; the necessary mechanical requirements regarding sample dissolution; and aids for accurate, fast and reliable polarization quantification. Herein, the challenges and limitations of each stage of a typical dissolutiondynamic nuclear polarization experiment are presented, with the focus being on how to quickly and simply overcome some of the limitations often encountered in the laboratory

Zero- to Ultralow-Field Nuclear Magnetic Resonance Enhanced with Dissolution Dynamic Nuclear Polarization

Zero- to ultralow-field nuclear magnetic resonance is a modality of magnetic resonance experiment which does not require strong superconducting magnets. Contrary to conventional high-field nuclear magnetic resonance, it has the advantage of allowing high resolution detection of nuclear magnetism through metal as well as within heterogeneous media. To achieve high sensitivity, it is common to couple zero-field nuclear magnetic resonance with hyperpolarization techniques. To date, the most common technique is parahydrogen-induced polarization, which is only compatible with a small number of compounds. In this article, we establish dissolution dynamic nuclear polarization as a versatile method to enhance signals in zero-field nuclear magnetic resonance experiments on virtually all small molecules with > 1 s relaxation times. We show as first examples J-spectra of hyperpolarized [13C]sodium formate, [1-13C]glycine and [2-13C]sodium acetate. We find signal enhancements of up to 11000 compared with thermal prepolarization in a 2 T permanent magnet. To increase the signal in future experiments, we investigate the relaxation effects of the TEMPOL radicals used for the hyperpolarization process at zero- and ultralow-field

Zero- to Ultralow-Field Nuclear Magnetic Resonance Enhanced with Dissolution Dynamic Nuclear Polarization

Zero- to ultralow-field nuclear magnetic resonance is a modality of magnetic resonance experiment which does not require strong superconducting magnets. Contrary to conventional high-field nuclear magnetic resonance, it has the advantage of allowing high-resolution detection of nuclear magnetism through metal as well as within heterogeneous media. To achieve high sensitivity, it is common to couple zero-field nuclear magnetic resonance with hyperpolarization techniques. To date, the most common technique is parahydrogen-induced polarization, which is only compatible with a small number of compounds. In this article, we establish dissolution dynamic nuclear polarization as a versatile method to enhance signals in zero-field nuclear magnetic resonance experiments on sample mixtures of [13C]sodium formate, [1-13C]­glycine, and [2-13C]sodium acetate, and our technique is immediately extendable to a broad range of molecules with >1 s relaxation times. We find signal enhancements of up to 11,000 compared with thermal prepolarization in a 2 T permanent magnet. To increase the signal in future experiments, we investigate the relaxation effects of the TEMPOL radicals used for the hyperpolarization process at zero- and ultralow-fields

Porous functionalized polymers enable generating and transporting hyperpolarized mixtures of metabolites

International audienceHyperpolarization 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 contaminantfree 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(13 C) = 25% within 8 min, through the combination of 1 H spin diffusion and 1 H → 13 C cross polarization. Solutions of 13 C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13 C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances