Article

The dynamic nuclear polarization process

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Abstract

The process of dynamic nuclear polarization (DNP) can be qualitatively understood by a simple heat contact between bodies of different heat capacities. These bodies are identified with the three thermal reservoirs corresponding to the electron Zeeman, the electron dipole–dipole and the nuclear Zeeman interaction. The primary cooling process itself, which consists of an off-resonance irradiation of the electron Zeeman reservoir, may be interpreted as a continuous and thus non-adiabatic demagnetization in the rotating frame of reference. In order to maximize the nuclear polarization in the case, when all three bodies are in contact with each other (EST model), it is immediately seen that the heat capacity of the electron dipolar reservoir has to be minimized. Furthermore, this graphical description is very helpful in illustrating, how the completely different approach to the DNP process, the solid effect model, can be implemented into the spin temperature theory.

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... Zu Beginn wird kurz das anschauliche Modell des Solid-State Effektes erläutert, gefolgt von einer Darstellung des differentiellen Solid State Effektes und der "Equal-Spin-Theorie" (kurz EST). Für ausführliche Informationen siehe auch [10]. ...
... Ist sie klein aber negativ, so beschreibt sie eine hohe negative Polarisation. Für ausführlichere Informationen zu diesem Thema ist [10] ein umfangreiche Quelle. ...
... Außerdem wurde festgestellt, dass die Kalibration der Peakpositionen nicht stimmte, was als Folge des Filamentaustauschs und Umbaus zu erklären ist. Nach einer ersten Nachkalibration erhielt man die Werte in der rechten Hälfte von 4.10.Zusammenfassen lassen sich die Ergebnisse der 1. Bestimmung der Verhältnisse von 3 He zu 4 He wie folgt:13:15 13:18 13:21 13:24 13:27 13:30 13:33 13:36 13:39 13:42 13:45 13:48 13:51 Abbildung 4.9: 1. Messung des 4 He-Tanks Abbildung 4.10: 1. Messung des 3 He-Tanks vor und nach der Kalibration der Peakposition • Verhältnis von 3 He zu ...
Thesis
The Polarized Target group in Bonn runs a polarized solid state target for double polarization experiments. It is a part of the Crystal Barrel experiment at the ELSA accelerator used to examine stimulated baryon spectra at the Physics Institute of the Bonn University. Extremely low temperatures are necessary during the polarization process and to keep the polarization in the frozen-spin-mode. A 3He/4He dilution cryostat is used. The cooling power of the dilution cryostat depends on the mixing ratio of 3He/4He, therefore a 3He/4He measuring system to monitor and optimize the performance of the dilution cryostat has been set up. This diploma thesis contains the conception and first tests of the monitoring system consisting of a quadrupole mass spectrometer and flowmeters. The tests have been carried out successfully.
... Thermal mixing, on the other hand, is dominant when the nuclear Larmor frequency is comparable to or less than the free radical ESR linewidth. 38 Even for a narrow linewidth radical such as trityl OX063, low γ nuclei meet this condition at the field considered in this work, so it is expected that 13 C and 2 H polarization will proceed by way of thermal mixing. 18,39,40 In this mechanism, spin systems are treated as thermodynamic heat reservoirs with an associated spin temperature. ...
... 18,39,40 In this mechanism, spin systems are treated as thermodynamic heat reservoirs with an associated spin temperature. 38,41,42 In particular, reservoirs include the nuclear and electron Zeeman systems (NZS and EZS) and the electron dipolar system (EDS). Thermodynamically, polarization transfer proceeds when microwave irradiation near the electron resonance brings the three reservoirs into thermal contact and "cools" the NZS to a spin temperature value below thermal equilibrium. ...
... 46 When 1 H is replaced with 2 H, the NZS of 2 H spins in the methyl groups is now brought into thermal contact with the EDS, thus increasing the total heat load for the EDS to cool, and thereby reducing the polarization enhancement. 21,25,38 A similar effect has been observed when 2 H-enrichment is used in the glassing solvents where the 13 C polarization is reduced significantly by 30-50%. 21,25 In the case of isotopic labeling of the substrate itself as in this work, 2 H labeling in the methyl group resulted in similar or slightly lower 13 C polarization compared to 13 C DNP of non-deuterated methyl 13 C spins, suggesting the extra 2 H NZS heat load of the deuterons in the methyl group is not as significant as the DNP effect of 2 H enrichment in the glassing matrix. ...
Article
Dynamic nuclear polarization (DNP) via the dissolution method has alleviated the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy by amplifying the signals by several thousand-fold. This NMR signal amplification process emanates from the microwave-mediated transfer of high electron spin alignment to the nuclear spins at high magnetic field and cryogenic temperature. Since the interplay between the electrons and nuclei is crucial, the chemical composition of a DNP sample such as the type of free radical used, glassing solvents, or the nature of the target nuclei can significantly affect the NMR signal enhancement levels that can be attained with DNP. Herein, we have investigated the influence of 13C isotopic labeling location on the DNP of a model 13C compound, sodium acetate, at 3.35 T and 1.4 K using the narrow electron spin resonance (ESR) linewidth free radical trityl OX063. Our results show that the carboxyl 13C spins yielded about twice the polarization produced in methyl 13C spins. Deuteration of the methyl 13C group, while proven beneficial in the liquid-state, did not produce an improvement in the 13C polarization level at cryogenic conditions. In fact, a slight reduction of the solid-state 13C polarization was observed when 2H spins are present in the methyl group. Furthermore, our data reveal that there is a close correlation between the solid-state 13C T1 relaxation times of these samples and the relative 13C polarization levels. The overall results suggest the achievable solid-state polarization of 13C acetate is directly affected by the location of the 13C isotopic labeling via the possible interplay of nuclear relaxation leakage factor and cross-talks between nuclear Zeeman reservoirs in DNP.
... 9,22,41,56,57 In the most current models of thermal mixing, the shape of the EPR spectrum as well as the electron T 1 of the radical used largely determine both the shape of the DNP spectrum and the maximum achievable polarization. 56,58,59 Though there is an only minimal change in trityl's EPR spectra with the addition of transition metal (Figure 4a), the electron T 1 measurement is more demonstrative. Electron T 1 for the sample optimally doped with manganese is drastically shortened with respect to the control sample, while the samples doped with copper and cobalt have T 1 values nearly identical to the control as shown in Figure 4b. ...
... As discussed above, polarization efficiency is determined in part by the electron T 1 of the free radical. [40][41][42]56,58,59 In the thermal mixing model of DNP, this is seen quite clearly as the minimum achievable spin temperature and hence maximum polarization is given by 56,58 In this equation, D is the EPR linewidth, T L is the lattice temperature, f is the nuclear relaxation leakage factor, ω e is the electron resonance frequency, and η is the ratio T 1e /T 1D of electron spin lattice relaxation time to the electron dipolar relaxation time. As T 1e is shortened, the lowest achievable spin temperature is reduced, which corresponds to higher polarization levels. ...
... As discussed above, polarization efficiency is determined in part by the electron T 1 of the free radical. [40][41][42]56,58,59 In the thermal mixing model of DNP, this is seen quite clearly as the minimum achievable spin temperature and hence maximum polarization is given by 56,58 In this equation, D is the EPR linewidth, T L is the lattice temperature, f is the nuclear relaxation leakage factor, ω e is the electron resonance frequency, and η is the ratio T 1e /T 1D of electron spin lattice relaxation time to the electron dipolar relaxation time. As T 1e is shortened, the lowest achievable spin temperature is reduced, which corresponds to higher polarization levels. ...
Article
Optimal efficiency of dissolution dynamic nuclear polarization (DNP) is essential to provide the required high sensitivity enhancements for in vitro and in vivo hyperpolarized 13C nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). At the nexus of the DNP process are the free electrons which provide the high spin alignment that is transferred to the nuclear spins. Without changing DNP instrumental conditions, one way to improve 13C DNP efficiency is by adding trace amounts of paramagnetic additives such as lanthanide (e.g. Gd3+, Ho3+, Dy3+, Tb3+) complexes to the DNP sample which has been observed to increase solid state 13C DNP signals by 100-250%. Herein, we have investigated the effects of paramagnetic transition metal complex R-NOTA (R=Mn2+, Cu2+, Co2+) doping on the efficiency of 13C DNP using trityl OX063 as the polarizing agent. Our DNP results at 3.35 T and 1.2 K show that doping the 13C sample with 3 mM Mn2+-NOTA led to a substantial improvement of the solid-state 13C DNP signal by a factor of nearly 3-fold. However, the other transition metal complexes Cu2+-NOTA and Co2+-NOTA complexes, despite their paramagnetic nature, had essentially no impact on solid-state 13C DNP enhancement. W-band electron paramagnetic resonance (EPR) measurements reveal that the trityl OX063 electron T1 was significantly reduced in Mn2+-doped samples but not in Cu2+- and Co2+-doped DNP samples. This work demonstrates, for the first time, that not all paramagnetic additives are beneficial to DNP. In particular, our work provides a direct evidence that electron T1 reduction of the polarizing agent by a paramagnetic additive is an essential requirement for the improvement seen in solid-state 13C DNP signal.
... The source of free electrons in DNP, mainly provided by stable organic free radicals, has a major impact in achieving the highest NMR signal enhancements. [17][18][19][20]39,40 The carboncentered trityl OX063, the free radical used in this study, has a narrow ESR linewidth that is suited for polarizing low-γ nuclei such as 13C . Numerous studies have shown that at least at B 0 =3.35 T and temperatures close to 1 K, the predominant DNP process that allows for polarization transfer from trityl OX063 electrons to low-γ nuclei such as 13 C and 89 Y is the thermal mixing DNP mechanism. ...
... 6,7,41,42 Thermal mixing occurs when the source of free electrons has ESR linewidth D that is larger than or comparable to the Larmor frequency ω n of the nucleus of interest. 1,2,40 In thermal mixing, a thermal contact is established between the electron dipolar system (EDS) and the nuclear Zeeman system (NZS) because of their compatible energies. Upon microwave irradiation, the spin temperature of EDS is lowered via dynamic cooling and due to the thermal link between the two reservoirs, the same low spin temperature is acquired by NZS. ...
... Upon microwave irradiation, the spin temperature of EDS is lowered via dynamic cooling and due to the thermal link between the two reservoirs, the same low spin temperature is acquired by NZS. 1,2,40 This process translates to higher nuclear spin population difference or polarization, thus amplified NMR signals. ...
Article
We have investigated the effects of Ho-DOTA doping on the dynamic nuclear polarization (DNP) of [1-(13)C] sodium acetate using trityl OX063 free radical at 3.35 T and 1.2 K. Our results indicate that addition of 2 mM Ho-DOTA on 3 M [1-(13)C] sodium acetate sample in 1 : 1 v/v glycerol : water with 15 mM trityl OX063 improves the DNP-enhanced (13)C solid-state nuclear polarization by a factor of around 2.7-fold. Similar to the Gd(3+) doping effect on (13)C DNP, the locations of the positive and negative (13)C maximum polarization peaks in the (13)C microwave DNP sweep are shifted towards each other with the addition of Ho-DOTA on the DNP sample. W-band electron spin resonance (ESR) studies have revealed that while the shape and linewidth of the trityl OX063 ESR spectrum was not affected by Ho(3+)-doping, the electron spin-lattice relaxation time T1 of trityl OX063 was prominently reduced at cryogenic temperatures. The reduction of trityl OX063 electron T1 by Ho-doping is linked to the (13)C DNP improvement in light of the thermodynamic picture of DNP. Moreover, the presence of Ho-DOTA in the dissolution liquid at room temperature has negligible reduction effect on liquid-state (13)C T1, in contrast to Gd(3+)-doping which drastically reduces the (13)C T1. The results here suggest that Ho(3+)-doping is advantageous over Gd(3+) in terms of preservation of hyperpolarized state-an important aspect to consider for in vitro and in vivo NMR or imaging (MRI) experiments where a considerable preparation time is needed to administer the hyperpolarized (13)C liquid.
... [7][8][9][10][11] Mounting evidence has shown that the narrow ESR linewidth trityl OX063 is a more efficient polarising agent for low-γ nuclei such as 13 C, 2 H, and 89 Y compared to broader linewidth free radicals such as TEMPO in the regime of 2-5 T and 1 K. 7,17,18 In the context of the thermal mixing DNP process, narrow ESR linewidths correspond to lower specific heat of the electron dipolar system, which eventually leads to a lower spin temperature of the nuclear Zeeman system. 7,19 Aside from the ESR linewidth D, the electron spin-lattice relaxation time T 1e of the paramagnetic center has also been implicated as a factor in achieving a lower spin temperature of the nuclear Zeeman system in DNP. 7,19,20 Thus, the ESR properties, namely the ESR linewidth and relaxation play a crucial role in attaining high nuclear polarization in DNP. ...
... 7,19 Aside from the ESR linewidth D, the electron spin-lattice relaxation time T 1e of the paramagnetic center has also been implicated as a factor in achieving a lower spin temperature of the nuclear Zeeman system in DNP. 7,19,20 Thus, the ESR properties, namely the ESR linewidth and relaxation play a crucial role in attaining high nuclear polarization in DNP. In this light, we have measured these two important ESR parameters of trityl OX063 at an optimum concentration for DNP (15 mM) 21 under various perturbations: temperature, magnetic field or ESR frequency (9.5 GHz, 95 GHz, 240 GHz, and 336 GHz), and in the presence of Gd 3+ , an electron T 1e relaxation agent known to enhance DNP, at 95 GHz. ...
... A key element to achieving the maximum nuclear polarization in the context of thermodynamic model of DNP is to minimize the spin temperature T s of the nuclear spin system defined by T s =(2D/ω e )T L [η(1+f)] 1/2 , where D is the ESR linewidth, ω e is the electron Larmor frequency, T L is the lattice temperature or the operating temperature of the polarizer, f is the nuclear relaxation leakage factor, and η is the ratio of the electron Zeeman relaxation time T 1e,Z over electron dipolar relaxation time T 1e,D . 7,19 Based on this equation, a minimum T s of the nuclear spin system and henceforth higher nuclear polarization in the thermal mixing regime can be achieved by: (i) using a free radical with small ESR linewidth D (ii) lower lattice temperature T L (lower operating temperature of the polarizer) (iii) higher microwave frequency/increased magnetic field (iv) low nuclear relaxation "leakage" factor f, which refers to relaxation pathways other than through the electron dipolar system and (v) having a minimal value of η. It should be noted that these trends are expected for DNP of low-γ nuclear spins where the dominant DNP mechanism is thermal mixing, 7,17,18,29 a condition achieved when the ESR linewidth D is greater than or comparable to the nuclear Larmor frequency ω n . ...
Article
We have performed temperature-dependent electron spin resonance (ESR) measurements of the stable free radical trityl OX063, an efficient polarizing agent for dissolution dynamic nuclear polarization (DNP), at the optimum DNP concentration (15 mM). We have found that (i) when compared to the W-band electron spin-lattice relaxation rate T1e(-1) of other free radicals used in DNP at the same concentration, trityl OX063 has slower T1e(-1) than BDPA and 4-oxo-TEMPO. At T > 20 K, the T1e(-1)vs. T data of trityl OX063 appears to follow a power law dependence close to the Raman process prediction whereas at T < 10 K, electronic relaxation slows and approaches the direct process behaviour. (ii) Gd(3+) doping, a factor known to enhance DNP, of trityl OX063 samples measured at W-band resulted in monotonic increases of T1e(-1) especially at temperatures below 20-40 K while the ESR lineshapes remained essentially unchanged. (iii) The high frequency ESR spectrum can be fitted with an axial g-tensor with a slight g-anisotropy: gx = gy = 2.00319(3) and gz = 2.00258(3). Although the ESR linewidth D monotonically increases with field, the temperature-dependent T1e(-1) is almost unchanged as the ESR frequency is increased from 9.5 GHz to 95 GHz, but becomes faster at 240 GHz and 336 GHz. The ESR properties of trityl OX063 reported here may provide insights into the efficiency of DNP of low-γ nuclei performed at various magnetic fields, from 0.35 T to 12 T.
... While a detailed treatment of the cooling process is given by Abragam and Goldman 1 and has recently been reformulated by Goertz et al., 33 to the best of our knowledge, the nature of the electron non-Zeeman reservoir has not been described in detail. In addition, the physical process enabling the coupling between the electron non-Zeeman reservoir and the nuclear Zeeman reservoirs has also not been treated in detail in the literature. ...
Article
Full-text available
Dynamic nuclear polarization (DNP) in combination with subsequent dissolution of the sample allows the detection of low-𝛾𝛾 nuclei in solution state with a signal gain of tens of thousands compared to experiments starting from Boltzmann conditions. The long polarization build-up times of typically more than one hour are a drawback of this technique. The combination of dissolution DNP with crosspolarization (CP) in the solid state was shown to have the potential to overcome this disadvantage. In this article we discuss the cross-polarization step under dissolution DNP conditions in more detail. We show that adiabatic half-passage pulses allow us to enhance the CP efficiency in power-limited DNP probes. As a low-power alternative to Hartmann-Hahn CP we also demonstrate the applicability of frequency-swept de- and re-magnetization pulses for polarization transfer via dipolar order. We investigate implications and restrictions of the common solid-state DNP mechanisms to the DNP–CP technique and apply a spin-thermodynamic model based on the thermal-mixing mechanism. The model allows us to investigate the dynamics of the polarization levels in a system with two nuclear Zeeman reservoirs and explains the enhanced DNP efficiency upon solvent deuteration within a spinthermodynamic picture.
... The ESR linewidth of nitroxyl radicals is generally larger than the 1 H Larmor frequency (143 MHz at 3.35 T) and therefore, it is expected that the EDS and the nuclear Zeeman system involving all NMR-active nuclei in the sample ( 1 H, 2 H and 13 C) are in thermal contact. 1,18 The specific heat capacity (C Z ) of the nuclear Zeeman system is approximately given by C Z~N Ω n 2 where N is the number of nuclear spins.18 Since C Z (2H)<C Z (1H), replacement of 1H (γ=42.577 ...
Article
Replacement of protons by deuterons in the glassing solvents led to 2-3-fold improvement of the (13)C dynamic nuclear polarization (DNP) solid-state NMR signal for samples doped with large electron spin resonance (ESR) linewidth free radicals galvinoxyl, DPPH, and 4-oxo-TEMPO. Meanwhile, the reverse effect is observed for (13)C DNP using small ESR linewidth free radicals BDPA and trityl OX063.
... In magnetic resonance imaging (MRI), the spatial resolution 64 and sensitivity are closely related to the induction of the sta- 149 Finally, in a DNP technique, electron spin polarization is 150 transferred onto the nuclear spin system using microwave 151 irradiation. Four effects are thought to contribute to DNP: 152 the Overhauser effect [7,23], the solid-effect [24], the cross- 153 effect [25], and thermal mixing [26]. 154 DNP technique was used to polarize 1 H, 13 C, 15 N, 31 P, and 155 other nuclei [4, 27,28]. ...
Article
Hyperpolarized ¹³C tracers offer a radiation-free option for metabolic imaging. Signal enhancement of an order of several thousand times with the dynamic nuclear polarization (DNP) technique allows the detection of these tracers and their immediate metabolites in living organisms with MRI/MRSI (magnetic resonance imaging/magnetic resonance spectroscopy imaging) methods in real time and with high temporal resolution. The initial ‘target’ application for DNP hyperpolarized tracers was prostate cancer, a condition that could hardly be diagnosed with the FDG PET. However, several Phase 2 clinical trials currently involve not only patients with prostate cancer but also pancreatic cancer, amyotrophic lateral sclerosis, transient ischemic attack, glioblastoma multiforme, mycosis fungiodes (skin cancer), and chronic heart failure. A large number of trials that started in the last three years indicate that there could be a potential for the application of hyperpolarized ¹³C labeled pyruvate in the diagnosis of several conditions other than prostate cancer. One limitation for the hyperpolarized ¹³C-labelled tracers is their relatively short half-life. In this review, we discuss several emerging strategies for increasing tracer’s lifetime that could allow either their transportation between facilities or improve the signal-to-noise ratio in the final acquisition. We also discuss some promising diagnostic applications.
... The quantitative theoretical treatment of this picture, including some additional assumptions, provides an upper limit for the nuclear polarization, depending on the nuclear spin I, the inverse lattice temperature β L = /kT , the electronic and nuclear Larmor frequencies ω e and ω I , the EPR linewidth D, the ratio of the electronic Zeeman and dipolar relaxation times η = t Z /t D , and the "leakage factor" f containing all nuclear relaxation processes, which do not process via the electronic dipolar reservoir. A more detailed description of these processes is given in [24]. In Fig. 1, this dependency is shown by a representative set of deuteron polarization values as a function of the EPR linewidth. ...
Article
Magnetic Resonance Imaging (MRI) is one of the most powerful non-invasive techniques in medical diagnostics that provides spatial and functional information. The sensitivity of NMR, imaging or spectroscopy, is strongly limited by the low Boltzmann polarization that can be reached at room temperature and any achievable field strength. A way out is the use of the Dynamic Nuclear Polarization (DNP) scheme, used for the operation of polarized solid targets in numerous nuclear and particle physics experiments since the early 1960s. Several imaging applications will benefit from the strong DNP-signal, e.g., available from hyperpolarized ¹³C-labeled contrast agents. The input and present status of DNP-hyperpolarization in this new emerging field is presented.
... [54][55][56] Unlike the solid effect (SE) 57 and the cross effect (CE), 54,58 TM is a many-spin model for polarization that treats spin interactions as thermodynamic reservoirs. 24,59 Namely, these reservoirs are the nuclear Zeeman system (NZS) and electron Zeeman system (EZS), and the electron dipolar system (EDS). In terms of this model, the polarization method may be qualitatively understood as microwave irradiation cooling the EDS and subsequent thermal contact with the NZS (via the hyperfine interaction), leading to a decrease in the NZS spin temperature, i.e., an increase in nuclear polarization. ...
Article
Dynamic nuclear polarization (DNP) is a technique that uses a microwave-driven transfer of high spin alignment from electrons to nuclear spins. This is most effective at low temperature and high magnetic field, and with the invention of the dissolution method, the amplified nuclear magnetic resonance (NMR) signals in the frozen state in DNP can be harnessed in the liquid-state at physiologically acceptable temperature for in vitro and in vivo metabolic studies. A current optimization practice in dissolution DNP is to dope the sample with trace amounts of lanthanides such as Gd³⁺ or Ho³⁺, which further improves the polarization. While Gd³⁺ and Ho³⁺ have been optimized for use in dissolution DNP, other lanthanides have not been exhaustively studied for use in C13 DNP applications. In this work, two additional lanthanides with relatively high magnetic moments, Dy³⁺ and Tb³⁺, were extensively optimized and tested as doping additives for C13 DNP at 3.35 T and 1.2 K. We have found that both of these lanthanides are also beneficial additives, to a varying degree, for C13 DNP. The optimal concentrations of Dy³⁺ (1.5 mM) and Tb³⁺ (0.25 mM) for C13 DNP were found to be less than that of Gd³⁺ (2 mM). W-band electron paramagnetic resonance shows that these enhancements due to Dy³⁺ and Tb³⁺ doping are accompanied by shortening of electron T1 of trityl OX063 free radical. Furthermore, when dissolution was employed, Tb³⁺-doped samples were found to have similar liquid-state C13 NMR signal enhancements compared to samples doped with Gd³⁺, and both Tb³⁺ and Dy³⁺ had a negligible liquid-state nuclear T1 shortening effect which contrasts with the significant reduction in T1 when using Gd³⁺. Our results show that Dy³⁺ doping and Tb³⁺ doping have a beneficial impact on C13 DNP both in the solid and liquid states, and that Tb³⁺ in particular could be used as a potential alternative to Gd³⁺ in C13 dissolution DNP experiments.
... Furthermore, in heteronuclear correlation experiments (e.g. 2 H-13 C), MAS narrows the first order 2 H quadrupole interaction and the resolution can be further improved if a 2 H double-quantum ( 2 H-DQ) excitation and reconversion scheme is employed. 11,13,14 NMR signal intensities of solids and liquids can be enhanced by several orders of magnitude with dynamic nuclear polarization (DNP) 15,16 and in the last decade high-frequency DNP has emerged as a valuable method for a variety of applications, spanning particle physics, 17,18 pharmaceutical applications 19,20 and structural and mechanistic studies of biologically relevant molecules. 15,21,22 In a DNP experiment, the large thermal polarization of a paramagnetic polarizing agent is transferred to surrounding nuclei by microwave irradiation of the sample at the electron paramagnetic resonance (EPR) transition. ...
Article
Full-text available
Perdeuteration of biological macromolecules for magic angle spinning solid-state NMR spectroscopy can yield high-resolution (2)H-(13)C correlation spectra and the method is therefore of great interest for the structural biology community. Here we demonstrate that the combination of sample deuteration and dynamic nuclear polarization yields resolved (2)H-(13)C correlation spectra with a signal enhancement of epsilon > or = 700 compared to a spectrum recorded with microwaves off and otherwise identical conditions. To our knowledge, this is the first time that (2)H-DNP has been employed to enhance MAS-NMR spectra of a biologically relevant system. The DNP process is studied using several polarizing agents and the technique is applied to obtain (2)H-(13)C correlation spectra of U-[(2)H, (13)C] proline.
... A thermal link is established between the nuclear Zeeman system and ESSI due to their comparable energies, thus in the end, the nuclear spins acquire the same lower spin temperature as the ESSI reservoir, translating to higher nuclear polarization. 8,32,56,57 In the thermal mixing model of DNP, the maximum achievable polarization for spin-1/2 nuclei is given by: [58][59][60] P max = tanh β L ω ε ω I 4D 1 η 1 + f (2) In the above equation, β L refers to the inverse lattice temperature, ω to the electron or nuclear Larmor frequency, D to the dipolar width of the EPR spectrum, η to the ratio of electronic and dipolar relaxation times (T 1e /T D ), and f to a nuclear relaxation leakage factor. ...
Article
Attainment of high NMR signal enhancements is crucial to the success of in vitro or in vivo hyperpolarized NMR or imaging (MRI) experiments. In this work, we report on the use of a superparamagnetic iron oxide nanoparticle (SPION) MRI contrast agent Feraheme (ferumoxytol) as a beneficial additive in 13C samples for dissolution dynamic nuclear polarization (DNP). Our DNP data at 3.35 T and 1.2 K reveal that addition of 11 mM elemental iron concentration of Feraheme in trityl OX063-doped 3 M [1-13C] acetate samples resulted in a substantial improvement of 13C DNP signal by a factor of almost 3-fold. Concomitant with the large DNP signal increase is the narrowing of the 13C microwave DNP spectra for samples doped with SPION. W-band electron paramagnetic resonance (EPR) spectroscopy data suggest that these two prominent effects of SPION doping on 13C DNP can be ascribed to the shortening of trityl OX063 electron T1 as explained within the thermal mixing DNP model. Liquid-state 13C NMR signal enhancements as high as 20,000-fold for SPION-doped samples were recorded after dissolution at 9.4 T and 297 K, which is about 3 times the liquid-state NMR signal enhancement of the control sample. While the presence of SPION in hyperpolarized solution drastically reduces 13C T1, this can be mitigated by polarizing smaller aliquots of DNP samples. Moreover, we have shown that Feraheme nanoparticles (~30 nm in size) can be easily and effectively removed from the hyperpolarized liquid by simple mechanical filtration, thus one can potentially incorporate an in-line filtration for these SPIONS along the dissolution pathway of the hyperpolarizer—a significant advantage over other DNP enhancers such as the lanthanide complexes. The overall results suggest that the commercially-available and FDA-approved Feraheme is a highly efficient DNP enhancer that could be readily translated for use in clinical applications of dissolution DNP.
... Thus, in the last decade high-frequency DNP has emerged as a valuable method to overcome the intrinsic low sensitivity of liquid and solid-state NMR experiments. [3][4][5] In particular, with its increased signal intensities, DNP is of significant interest in applications ranging from particle physics [6] to structural biology [4,5] and clinical imaging. [7] Recent DNP experiments have been directed at enhancing signal intensities in both solid and liquid state NMR spectra. ...
Article
Full-text available
In situ High-Field Dynamic Nuclear Polarization: Direct and indirect polarization of [superscript 13]C nuclei by DNP is investigated (see graphic). The field-dependent enhancement profile for both processes are investigated and the bulk polarization build-up time constants τ[C over B] and τ[H over B] for direct and indirect [superscript 13]C polarization are compared.
... It also has the added advantage of being readily removed from the sample prep after dissolution, as it is insoluble in water and can be easily filtered. 28 To first approximation, the linewidth of the radical is equivalent to the heat capacity of the electron dipolar system in TM. 33 Therefore, with the condition that the ESR linewidth exceeds the nuclear Larmor frequency, a more narrow line should produce greater nuclear polarization. BDPA displays almost no g-anisotropy, and produces a microwave frequency sweep spectrum even narrower than trityl. ...
Article
Full-text available
Polarization transfer from unpaired electron radicals to nuclear spins at low-temperature is achieved using microwave irradiation by a process broadly termed dynamic nuclear polarization (DNP). The resulting signal enhancement can...
... This last technique is far from recent; it was proposed by Jeffries [27], Erb et al. [28], and by Abragam and Proctor [29]. Also called the ''solid effect", it differs from the Overhauser effect in that it requires a static interaction between electrons and nuclei and that forbidden transitions (at a frequency equal to the sum or difference of the electron and nucleus Larmor frequencies) are driven [30]. For a long time, the main application was the production of polarised Cross-section Side view 100 µm copper dielectric sample Fig. 2. Outline of the microstrip/microslot probe of Maguire et al. [23] shown in cross-section and side-view. ...
Article
In vivo or ex vivo microbiological nuclear magnetic resonance (NMR) study was conducted on compounds such as whole cells, cell extracts, culture media, and soil samples. The results of the study show that high resolution magic angle spinning (HR-MAS) have profiles similar to those observed for purified polysaccharides analyzed by solution NMR. Nutrient starvation and non-culturability of bacteria leads to changes in metabolism, while examination of lactococci show that cells enter a non-culturable state after carbohydrate depletion and become incapable of growth on solid media. HPLC and 13C NMR analysis show that a mutant overexpressing mannitol 1-phosphate dehydrogenase, lacking lactate dehydrogenase and maintained in the resting state can transform 25% of the supplied glucose in mannitol. Riboflavin is found to be produced by a suitably engineered strain of Bacillus subtilis, while isoleucine is shown to be synthesized by a split pathway.
Article
Full-text available
Dynamic Nuclear Polarisation (DNP) was suggested for the first time by Albert Overhauser in early 1950s. In DNP experiments the polarisation from electrons can be transferred to nuclei by irradiation of the electron resonance line. There are several possible mechanisms for polarisation transfer that involve DNP in solid state depending on the width of the electron line in respect to the nuclear Larmor frequency. In this thesis, the efficiency of TEMPO radical (2,2,6,6 tetramethilpiperidine, 1 oxyl) for DNP is demonstrated in combination with nuclear polarisation transfer techniques for dissolution experiments. New cryo-probes were developed for DNP and cross polarisation (CP) for operation temperatures as low as 1.5 K. Two of them were designed for dissolution experiments. Some published sequences of nuclear polarisation transfer were tested at low temperatures and compared. Novel sequences were implemented for efficient CP in organic samples doped with TEMPO to allow for a consecutive dissolution experiment. The combination of DNP with new CP sequences at low temperatures, achieved at least twice the 13C polarisation obtained with DNP and in a substantially shorter time (between 5 to 10 minutes) in samples doped with TEMPO. The polarisation levels obtained in samples of [13C-1] labelled Na acetate in a few minutes was comparable to the polarisation obtained with trityl radicals in a few hours. In addition, another strategy was investigated by using brute force polarisation as a mechanism for achieving large levels of nuclear spin order. The problem presented by this method is the long relaxation time required to obtain the thermal equilibrium polarisation. By doping with lanthanides samples of [13C-1] labelled Na acetate in 1:1 glycerol-water, it was possible to obtain thermal equilibrium for a 13C spin system in less than one hour.
Article
Hyperpolarized (89)Y complexes are attractive NMR spectroscopy and MR imaging probes due to the exceptionally long spin-lattice relaxation time (T(1) ≈ 10 min) of the (89)Y nucleus. However, in vivo imaging of (89)Y has not yet been realized because of the low NMR signal enhancement levels previously achieved for this ultra low-γ(n) nucleus. Here, we report liquid-state (89)Y NMR signal enhancements over 60,000 times the thermal signal at 298 K in a 9.4 T magnet, achieved after the dynamic nuclear polarization (DNP) of Y(III) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) samples at 3.35 T and 1.4 K. The (89)Y DNP was shown to proceed by thermal mixing and the liquid state (89)Y NMR signal enhancement was maximized by (i) establishing the optimal microwave irradiation frequency, (ii) optimizing the glassing matrix, (iii) choosing a radical with negligible inhomogeneous line broadening contribution to the ESR linewidth, and (iv) addition of an electron T(1e) relaxation agent. The highest enhancements were achieved using a trityl OX063 radical combined with a gadolinium relaxation agent in water-glycerol matrix. Co-polarization of (89)YDOTA and sodium [1-(13)C]pyruvate showed that both (89)Y and (13)C nuclear species acquired the same spin temperature, consistent with thermal mixing theory of DNP. This methodology may be applicable for the optimization of DNP of other low-γ(n) nuclei.
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Nuclear magnetic resonance (NMR) spectroscopy is a broadly used analytical method with major applications in chemistry, biochemistry and medicine. Key applications include structural analysis of small molecules, metabolites, larger biomolecules such as proteins, RNA and DNA, and applications in material science. Magnetic resonance imaging (MRI), which is based on the same physical principles, is extensively used in medical diagnostics and represents the most widespread application of NMR. However, NMR is fundamentally limited in sensitivity and this has always restricted its applicability. Hyperpolarization techniques such as dynamic nuclear polarization (DNP) have become a major field of research and development because they hold the promise of increasing the sensitivity of NMR by several orders of magnitude. Such sensitivity enhancements could significantly broaden NMR applications, combining its unique structural information with much higher sensitivity. Unfortunately, there is no single implementation of DNP that would be suitable for a broader range of typical NMR applications. Experimental conditions often circumscribe areas of possible applications. Nevertheless, recent developments point towards experimental protocols providing solutions for specific applications of NMR. This review summarizes the concepts behind DNP in the light of recent developments and potential applications.
Article
Hyperpolarized [1-(13)C]pyruvate has become an important diagnostic tracer of normal and aberrant cellular metabolism for in vitro and in vivo NMR spectroscopy (MRS) and imaging (MRI). In pursuit of achieving high NMR signal enhancements in dynamic nuclear polarization (DNP) experiments, we have performed an extensive investigation of the influence of Gd(3+) doping, a parameter previously reported to improve hyperpolarized NMR signals, on the DNP of this compound. [1-(13)C]Pyruvate samples were doped with varying amounts of Gd(3+) and fixed optimal concentrations of free radical polarizing agents commonly used in fast dissolution DNP: trityl OX063 (15 mM), 4-oxo-TEMPO (40 mM), and BDPA (40 mM). In general, we have observed three regions of interest, namely, (i) a monotonic increase in DNP-enhanced nuclear polarization P(dnp) upon increasing the Gd(3+) concentration until a certain threshold concentration c(1) (1-2 mM) is reached, (ii) a region of roughly constant maximum P(dnp) from c(1) until a concentration threshold c(2) (4-5 mM), and (iii) a monotonic decrease in P(dnp) at Gd(3+) concentration c > c(2). Of the three free radical polarizing agents used, trityl OX063 gave the best response to Gd(3+) doping, with a 300% increase in the solid-state nuclear polarization, whereas addition of the optimum Gd(3+) concentration on BDPA and 4-oxo-TEMPO-doped samples only yielded a relatively modest 5-20% increase in the base DNP-enhanced polarization. The increase in P(dnp) due to Gd(3+) doping is ascribed to the decrease in the electronic spin-lattice relaxation T(1e) of the free radical electrons, which plays a role in achieving lower spin temperature T(s) of the nuclear Zeeman system. These results are discussed qualitatively in terms of the spin temperature model of DNP.
Article
The polarization (static or dynamic) of HD material requires very pure HD samples, with H2 and D2 impurities concentrations smaller than 0.1%. A new distillation apparatus equipped with a mass spectrometer has been built. It allows reaching such a level of purity and also measurement of the H2 and D2 residual concentrations down to 0.05%. The NMR spin–lattice relaxation times and have also been measured. The apparatus is described as well as the distillation method. and data as a function of [H2] and [D2] concentrations are given, at 0.85 T and 1.8 K.
Chapter
Dynamic nuclear polarization (DNP) was first demonstrated in the early days of NMR spectroscopy. The technique involves the transfer of large spin polarization from unpaired electron spins to neighboring nuclei using microwave irradiation close to the electron Larmor frequency. Over the years, although a number of applications in solid-state NMR have been demonstrated, the use of DNP in liquid-state experiments has been more limited. Modern technological advances now mean that DNP is undergoing a rejuvenation as a technique to vastly improve the sensitivity of NMR. This article describes the current state of the art in regard to the liquid-state applications of DNP, including sensitivity enhancement in heteronuclear NMR spectroscopy.
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The objective of this study is to investigate if trityl biradicals could lead to more efficient dynamic nuclear polarization (DNP) for low gamma nuclear spins at low temperature (approximately 1 K) than a trityl monoradical. Three novel trityl biradicals of different size are synthesized, characterized and employed for hyperpolarization of [1-(13)C]pyruvic acid at 3.35 T and 4.64 T. Intramolecular electron-electron distances are obtained via dipolar couplings from electron paramagnetic resonance (EPR) spectroscopy at X-band and W-band that match well with calculated molecular structures. Steady-state DNP levels and build-up times are measured as function of radical concentration, magnetic field strength and microwave frequency for each biradical. Similar maximal DNP is obtained with all studied biradicals whereas a twice as high polarization is achievable with the monoradical. Both the biradicals and the monoradical show approximately a doubling of the polarization when increasing the field strength from 3.35 T to 4.64 T. Biradical concentrations at maximum polarization are several times lower than the optimum monoradical concentration, but the penalty is a much longer build-up time. Adding a small amount of Gd(3+) to the samples (molar fraction of typically 100 ppm) has the same effect on DNP with the biradicals as with the monoradical. The electron longitudinal relaxation time T(1e) is found to be independent of the radical type and the field strength in this study. The same dependence of T(1e) on the trityl concentration is observed for all radicals. A considerable shortening of the (13)C longitudinal relaxation time is observed for biradicals which agrees with the shortened build-up time compared to the monoradical at the same trityl concentration. This is probably the reason for lower DNP levels with trityl biradicals.
Article
Dynamic nuclear polarization is a method which allows for a dramatic increase of the NMR signals due to polarization transfer between electrons and their neighboring nuclei, via microwave irradiation. These experiments have become popular in recent years due to the ability to create hyper-polarized chemically and biologically relevant molecules, in frozen glass forming mixtures containing free radicals. Three mechanisms have been proposed for the polarization transfer between electrons and their surrounding nuclei in such non-conducting samples: the solid effect and cross effect mechanisms, which are based on quantum mechanics and relaxation on small spin systems, and thermal mixing, which originates from the thermodynamic macroscopic notion of spin temperature. We have recently introduced a spin model, which is based on the density matrix formalism and includes relaxation, and applied it to study the solid effect and cross effect mechanisms on small spin systems. In this publication we use the same model to describe the thermal mixing mechanism, and the creation of spin temperature. This is obtained without relying on the spin temperature formalism. Simulations of small model systems are used on systems with homogeneously and inhomogeneously broadened EPR lines. For the case of a homogeneously broadened line we show that the nuclear enhancement results from the thermal mixing and solid effect mechanisms, and that spin temperatures are created in the system. In the inhomogeneous case the enhancements are attributed to the solid effect and cross effect mechanisms, but not thermal mixing.
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A new polarizing agent with superior performance in dynamic nuclear polarization experiments is introduced, and utilizes two TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) moieties connected through a rigid spiro tether (see structure). The observed NMR signal intensities were enhanced by a factor of 1.4 compared to those of TOTAPOL, a previously described TEMPO-based biradical with a flexible tether.
Article
Many approaches are now available for achieving high levels of nuclear spin polarization. One of these methods is based on the notion that as the temperature is reduced, the equilibrium nuclear polarization will increase, according to the Boltzmann distribution. The main problem with this approach is the length of time it may take to approach thermal equilibrium at low temperatures, since nuclear relaxation times (characterized by the spin-lattice relaxation time T1) can become very long. Here, we show, by means of relaxation time measurements of frozen solutions, that selected lanthanide ions, in the form of their chelates with DTPA, can act as effective relaxation agents at low temperatures. Differential effects are seen with the different lanthanides that were tested, holmium and dysprosium showing highest relaxivity, while gadolinium is ineffective at temperatures of 20 K and below. These observations are consistent with the known electron-spin relaxation time characteristics of these lanthanides. The maximum relaxivity occurs at around 10 K for Ho-DTPA and 20 K for Dy-DTPA. Moreover, these two agents show only modest relaxivity at room temperature, and can thus be regarded as relaxation switches. We conclude that these agents can speed up solid state NMR experiments by reducing the T1 values of the relevant nuclei, and hence increasing the rate at which data can be acquired. They could also be of value in the context of a simple low-cost method of achieving several-hundred-fold improvements in polarization for experiments in which samples are pre-polarized at low temperatures, then rewarmed and dissolved immediately prior to analysis.
Article
Diseased tissue is often characterized by abnormalities in intermediary metabolism. Observing these alterations in situ may lead to an improved understanding of pathological processes and novel ways to monitor these processes noninvasively in human patients. Although (13)C is a stable isotope safe for use in animal models of disease as well as human subjects, its utility as a metabolic tracer has largely been limited to ex vivo analyses employing analytical techniques like mass spectrometry or nuclear magnetic resonance spectroscopy. Neither of these techniques is suitable for noninvasive metabolic monitoring, and the low abundance and poor gyromagnetic ratio of conventional (13)C make it a poor nucleus for imaging. However, the recent advent of hyperpolarization methods, particularly dynamic nuclear polarization (DNP), makes it possible to enhance the spin polarization state of (13)C by many orders of magnitude, resulting in a temporary amplification of the signal sufficient for monitoring kinetics of enzyme-catalyzed reactions in living tissue through magnetic resonance spectroscopy or magnetic resonance imaging. Here, we review DNP techniques to monitor metabolism in cultured cells, perfused hearts, and perfused livers, focusing on our experiences with hyperpolarized [1-(13)C]pyruvate. We present detailed approaches to optimize the DNP procedure, streamline biological sample preparation, and maximize detection of specific metabolic activities. We also discuss practical aspects in the choice of metabolic substrates for hyperpolarization studies and outline some of the current technical and conceptual challenges in the field, including efforts to use hyperpolarization to quantify metabolic rates in vivo.
Article
In order to facilitate versatile applications with high field dynamic nuclear polarization (DNP), it is important to be able to optimize the DNP performance, i.e. reach high nuclear hyperpolarization within a short signal build up time. Given that the solid-state DNP process is strongly temperature-dependent, it is important to benchmark the temperature dependence of various DNP and electron paramagnetic resonance (EPR) parameters that can then be used to test and develop theories and models for high field DNP mechanisms. However, DNP and EPR experiments at high fields and cryogenic temperatures below 20 Kelvin usually require home built instrumentation, and therefore even basic experimental observations are lacking in the literature. DNP and EPR experiments at 7 T (197 GHz) and 8.5 T (240 GHz), respectively, were conducted at temperatures between 35 K and 3.7 K where the electron thermal polarization changes from 13.4% to 85.6%, respectively. The samples are frozen solutions of 15 mM OX063Me trityl radicals in various mixtures of [1-(13)C]pyruvic acid, glycerol, and Gd(3+)-chelates. For all sample mixtures, the trityl EPR lines are found to be inhomogeneously broadened and the dominant DNP mechanism is shown to be the cross effect (CE). A 20%, 11%, and 6.77% (13)C polarization is achieved at 3.7 K with a [1-(13)C]pyruvic-glycerol-H2O sample, the addition of 2 mM of Gd(3+)-chelates, and pure [1-(13)C]pyruvic acid, respectively. When T1n is sufficiently long, our results seem to suggest T1e is a key variable in the DNP process, where longer T1e values correlate with larger DNP enhancements (εDNP). The experimental data reported here on the temperature dependence of T1n, T1e, Tm (electron phase memory time), the EPR linewidth, TDNP and εDNP at high fields will be helpful for testing the mechanism and theory of DNP processes.
Article
Dynamic nuclear polarization (DNP) has become a very important hyperpolarization method because it can dramatically increase the sensitivity of nuclear magnetic resonance (NMR) of various molecules. Liquid-state DNP based on Overhauser effect is capable of directly enhancing polarizations of all kinds of nuclei in the system. The combination of simultaneous Overhauser multi-nuclei enhancements with the multi-nuclei parallel acquisitions provides a variety of important applications in both MR spectroscopy (MRS) and image (MRI). Here we present two simple illustrative examples for simultaneously enhanced multi-nuclear spectra and images to demonstrate the principle and superiority. We have observed very large simultaneous DNP enhancements for different nuclei, such as 1H and 23Na, 1H and 31P, 19F and 31P, especially for the first time to report sodium ion enhancement in liquid. We have also obtained the simultaneous imaging of 19H and 31P at low field by solution-state DNP for the first time. This method can obtain considerably complementary structure-determination information of miscellaneous biomolecules from a single measurement. It can also be used in combination with the fast acquisition schemes and quantitative analysis with reduced scan time.
Article
We present the design, initial installation and test results of two corrugated waveguide transmission line systems for coupling terahertz power from gyrotrons to two different solid-state Dynamic Nuclear Polarization - Nuclear Magnetic Resonance (DNP-NMR) spectrometers at 600 MHz and 700 MHz (1H). The first system combines the power from two different tunable 460 GHz gyrotrons to the DNP-NMR experiment while the second line couples power from a single 395 GHz tunable gyrotron to the DNP-NMR experiment. The lines are currently being installed at the Institute of Protein Research in Osaka University. Test results of individual components and system level test results will be presented.
Article
We report the influence of glassing solvent deuteration and Gd3+ doping on 13C dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) performed on [1-13C] sodium acetate at B0 = 5 T and 1.2 K. Our data reveal that at 5 T, glassing solvent deuteration still results in a 40% improvement of the 13C DNP signal when a large electron spin resonance (ESR) linewidth 4-oxo-TEMPO free radical is used, but results in a 60% decrease of the DNP signal in the case of a sample doped with small ESR linewidth trityl OX063. An addition of a trace amount of the Gd3+ complex Gd–HP–DO3A led to a negligible slight decrease on the 13C polarization TEMPO-doped sample, but is still relatively beneficial for the trityl-doped sample with 30% improvement of the DNP-enhanced 13C polarization. These findings indicate that while these DNP optimization steps are still valid at 5 T, the effects are not as pronounced as observed in 13C DNP at B0 = 3.35 T. These DNP results at 5 T are discussed thermodynamically within the framework of the thermal mixing model of DNP.
Article
The nitroxide-based free radical TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) is a widely-used polarizing agent in NMR signal amplification via dissolution dynamic nuclear polarization (DNP). In this study, we have thoroughly investigated the effects of (15) N and/or (2) H isotopic labeling of 4-oxo-TEMPO free radical on (13) C DNP of 3 M [1- (13) C] sodium acetate samples in 1:1 v/v glycerol:water at 3.35 T and 1.2 K. Four variants of this free radical were used for (13) C DNP: 4-oxo-TEMPO, 4-oxo-TEMPO-(15) N, 4-oxo-TEMPO-d16 and 4-oxo-TEMPO-(15) N,d16 . Our results indicate that, despite the striking differences seen in the electron spin resonance (ESR) spectral features, the (13) C DNP efficiency of these (15) N and/or (2) H-enriched 4-oxo-TEMPO free radicals are relatively the same compared to (13) C DNP performance of the regular 4-oxo-TEMPO. Furthermore, when fully-deuterated glassing solvents were used, the (13) C DNP signals of these samples all doubled in the same manner and the (13) C polarization buildup was faster by a factor of two for all samples. The data here suggest that the hyperfine coupling contributions of these isotopically-enriched 4-oxo-TEMPO free radicals have negligible effects on the (13) C DNP efficiency at 3.35 T and 1.2 K. These results are discussed in light of the spin-temperature model of DNP.
Article
Dynamic nuclear polarization (DNP) via the dissolution method has become one of the rapidly emerging techniques to alleviate the low signal sensitivity in nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). In this paper, we report on the development and (13) C hyperpolarization efficiency of a homebuilt dynamic nuclear polarization (DNP) system operating at 6.423 T and 1.4 K. The DNP hyperpolarizer system was assembled on a wide-bore superconducting magnet, equipped with a standard continuous-flow cryostat, and a 180 GHz microwave source with 120 mW power output and wide 4 GHz frequency tuning range. At 6.423 T and 1.4 K, solid-state (13) C polarization P levels of 64% and 31% were achieved for 3 M [1-(13) C] sodium acetate samples in 1:1 v/v glycerol:water glassing matrix doped with 15 mM trityl OX063 and 40 mM 4-oxo-TEMPO, respectively. Upon dissolution which takes about 15 s to complete, liquid-state (13) C NMR signal enhancements as high as 240,000-fold (P = 21%) were recorded in a nearby high resolution (13) C NMR spectrometer at 1 T and 297 K. Considering the relatively lower cost of our homebuilt DNP system and the relative simplicity of its design, the dissolution DNP setup reported here could be feasibly adapted for in vitro or in vivo hyperpolarized (13) C NMR or MRI at least in the pre-clinical setting.
Article
Dissolution dynamic nuclear polarization (DNP) is one of the most successful techniques that resolves the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) by amplifying the signal by several thousand-fold. One way to further improve the DNP signal is the inclusion of trace amounts of lanthanides in DNP samples doped with trityl OX063 free radical as the polarizing agent. In practice, stable monomeric gadolinium complexes such as Gd-DOTA or Gd-HP-DO3A are used as beneficial additives in DNP samples, further boosting the DNP-enhanced solid-state 13C polarization by a factor of 2 or 3. Herein, we report on the use of a trimeric gadolinium complex as a dopant in 13C DNP samples to improve the 13C DNP signals in the solid-state at 3.35 T and 1.2 K and consequently, in the liquid-state at 9.4 T and 298 K after dissolution. Our results have shown that doping the 13C DNP sample with a complex which holds three Gd3+ ions led to an improvement of DNP-enhanced 13C polarization by a factor of 3.4 in the solid-state—on par with those achieved using monomeric Gd3+ complexes but only requires about one-fifth of the concentration. Upon dissolution, liquid-state 13C NMR signal enhancements close to 20,000-fold, approximately 3-fold the enhancement of the control samples, were recorded in the nearby 9.4 T high resolution NMR magnet at room temperature. Comparable reduction of 13C spin-lattice T1 relaxation time was observed in the liquid-state after dissolution for both the monomeric and trimeric Gd3+ complexes. Moreover, W-band electron paramagnetic resonance (EPR) data have revealed that 3-Gd doping significantly reduces the electron T1 of the trityl OX063 free radical, but produces negligible changes in the EPR spectrum, reminiscent of the results with monomeric Gd3+-complex doping. Our data suggest that the trimeric Gd3+ complex is a highly beneficial additive in 13C DNP samples and that its effect on DNP efficiency can be described in the context of the thermal mixing mechanism.
Article
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The nitroxide-based 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) free radical is widely used in ¹³C dynamic nuclear polarization (DNP) due to its relatively low cost, commercial availability, and effectiveness as polarizing agent. While a large number of TEMPO derivatives are available commercially, so far, only few have been tested for use in ¹³C DNP. In this study, we have tested and evaluated the ¹³C hyperpolarization efficiency of eight derivatives of TEMPO free radical with different side arms in the 4-position. In general, these TEMPO derivatives were found to have slight variations in efficiency as polarizing agents for DNP of 3 M [1-¹³C] acetate in 1:1 v/v ethanol:water at 3.35 T and 1.2 K. X-band electron paramagnetic resonance (EPR) spectroscopy revealed no significant differences in the spectral features among these TEMPO derivatives. ²H enrichment of the ethanol:water glassing matrix resulted in further improvement of the solid-state ¹³C DNP signals by factor of 2 to 2.5-fold with respect to the ¹³C DNP signal of non-deuterated DNP samples. These results suggest an interaction between the nuclear Zeeman reservoirs and the electron dipolar system via the thermal mixing mechanism.
Article
Hyperpolarization of ¹³C-enriched biomolecules via dissolution dynamic nuclear polarization (DNP) has enabled real-time metabolic imaging of a variety of diseases with superb specificity and sensitivity. The source of the unprecedented liquid-state nuclear magnetic resonance spectroscopic or imaging signal enhancements of >10 000-fold is the microwave-driven DNP process that occurs at a relatively high magnetic field and cryogenic temperature. Herein, we have methodically investigated the relative efficiencies of ¹³C DNP of single or double ¹³C-labeled sodium acetate with or without ²H-enrichment of the methyl group and using a 4-oxo-TEMPO free radical as the polarizing agent at 3.35 T and 1.4 K. The main finding of this work is that not all ¹³C spins in acetate are polarized with equal DNP efficiency using this relatively wide electron spin resonance linewidth free radical. In fact, the carbonyl ¹³C spins have about twice the solid-state ¹³C polarization level of methyl ¹³C spins. Deuteration of the methyl group provides a DNP signal improvement of methyl ¹³C spins on a par with that of carbonyl ¹³C spins. On the other hand, both the double ¹³C-labeled [1,2-¹³C2] acetate and [1,2-¹³C2, ²H3] acetate have a relative solid-state ¹³C polarization at the level of [2-¹³C] acetate. Meanwhile, the solid-state ¹³C T1 relaxation times at 3.35 T and 1.4 K were essentially the same for all six isotopomers of ¹³C acetate. These results suggest that the intramolecular environment of ¹³C spins plays a prominent role in determining the ¹³C DNP efficiency, while the solid phase ¹³C T1 relaxation of these samples is dominated by the paramagnetic effect due to the relatively high concentration of free radicals.
Article
Dynamic nuclear polarization (DNP) via the dissolution method is one of the most successful methods for alleviating the inherently low Boltzmann-dictated sensitivity in nuclear magnetic resonance (NMR) spectroscopy. This emerging technology has already begun to positively impact chemical and metabolic research by providing the much-needed enhancement of the liquid-state NMR signals of insensitive nuclei such as 13C by several thousand-fold. In this Perspective, we present our viewpoints regarding the key elements needed to maximize the NMR signal enhancements in dissolution DNP, from the very core of the DNP process at cryogenic temperatures, DNP instrumental conditions, chemical tuning in sample preparation, to current developments in minimizing hyperpolarization losses during the dissolution transfer process. The optimization steps discussed herein could potentially provide important experimental and theoretical considerations in harnessing the best possible sensitivity gains in NMR spectroscopy as afforded by optimized dissolution DNP technology.
Article
Glassing matrix deuteration could be a beneficial sample preparation method for ¹³C dynamic nuclear polarization (DNP) when large electron paramagnetic resonance (EPR) width free radicals are used. However, it could yield the opposite DNP effect when samples are doped with small EPR width free radicals. Herein, we have investigated the influence of solvent deuteration on the ¹³C nuclear and electron relaxation that go along with the effects on ¹³C DNP intensities at 3.35 T and 1.2 K. For ¹³C DNP samples doped with trityl OX063, the ¹³C DNP signals decreased significantly when the protons are replaced by deuterons in glycerol:water or DMSO:water solvents. Meanwhile, the corresponding solid-state ¹³C T1 relaxation times of trityl OX063-doped samples generally increased upon solvent deuteration. On the other hand, ¹³C DNP signals improved by a factor of ∼1.5 to 2 upon solvent deuteration of samples doped with 4-oxo-TEMPO. Despite this ¹³C DNP increase, there were no significant differences recorded in ¹³C T1 values of TEMPO-doped samples with nondeuterated or fully deuterated glassing matrices. While solvent deuteration appears to have a negligible effect on the electron T1 relaxation of both free radicals, the electron T2 relaxation times of these two free radicals generally increased upon solvent deuteration. These overall results suggest that while the solid-phase ¹³C DNP signals are dependent upon the changes in total nuclear Zeeman heat capacity, the ¹³C relaxation effects are related to ²H/¹H nuclear spin diffusion-assisted ¹³C polarization leakage in addition to the dominant paramagnetic relaxation contribution of free radical centers.
Article
We report enhancement of the spin polarization of $^{133}\mathrm{Cs}$ nuclei in CsH salt by spin transfer from an optically pumped cesium vapor. The nuclear polarization was 4.0 times the equilibrium polarization at 9.4 T and $137\text{ }\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$, with larger enhancements at lower fields. This work is the first demonstration of spin transfer from a polarized alkali vapor to the nuclei of a solid, opening up new possibilities for research in hyperpolarized materials.
Article
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We have reached +90.5% and -93.6% dynamic proton polarization in solid NH3 using paramagnetic radicals created by proton irradiation of 40 Mrad total dose. The dynamic polarization experiments were performed at 25 kG field in a dilution refrigerator. These results may indicate a breakthrough in the development of better polarized target materials for high-energy physics experiments.
Article
Nuclear spin-lattice relaxation times of Al27 in pure Al and Cu63 in annealed pure Cu have been measured with a nuclear induction spectrometer, by the method of saturation. The experimental values of T1 are 4.1±0.8 milliseconds for Al27 and 3.0±0.6 milliseconds for Cu63, in reasonable agreement with theory.The dispersion mode of the nuclear resonance was also observed, and it was found that χ′ (the real part of the rf susceptibility) does not saturate at the same level as the absorption, χ′′, but remains roughly constant out to a radio-frequency field intensity of about 2 gauss. Both χ′ and χ′′ become narrower and nearly Lorentzian in shape above saturation. When the dc magnetic field modulation is increased from 14 to 41 cps the phase of the dispersion signal lags behind the modulation, presumably because the modulation period is then comparable to T1. Large dispersion signals above saturation have also been observed for the Na23 resonance in NaCl.This behavior of the dispersion mode is in conflict with the predictions of Bloembergen, Purcell, and Pound and of the Bloch equations. The validity of these theories is re-examined, and it is concluded that although they are applicable to nuclear resonance in liquids and gases, and to solids at small rf intensities, they contain incorrect assumptions as applied to solids at high rf power levels. The theory of Bloembergen, Purcell, and Pound is based on an assumption equivalent to that of a spin temperature. It is shown that the spin state cannot be strictly described by a spin temperature because the phases of the spin quantum states are not incoherent, as required by the temperature concept. The transverse decay of the nuclear magnetization predicted by the Bloch equations is shown to be partially forbidden by energy and entropy considerations if a large rf field at the resonance frequency is continuously applied to the solid.A theory is developed which is applicable only to solids at rf magnetic field intensities well above the saturation level and which is in reasonable agreement with the experimental observations. The Hamiltonian is transformed to a coordinate system rotating at the frequency of the rf field. The resulting time-dependent parts of the spin-spin interaction are nonsecular perturbations on the time-independent part, and can therefore be ignored. Statistical mechanics is applied to the remaining stationary spin Hamiltonian; specifically it is assumed that the spin system is in its most probable macrostate (a canonical distribution of quantum states) with respect to the transformed spin Hamiltonian. This assumption is justified because the transformed spin Hamiltonian is effectively time independent and the spin-lattice interaction is small, and it is analogous to assumptions basic to classical acoustics and fluid mechanics. The spin-lattice interaction merely determines the expectation value of the transformed spin Hamiltonian, which can be readily calculated under the assumption that the expectation value of the spin angular momentum of each spin is relaxed independently to its thermal equilibrium value by the lattice in time T1. Both fast and slow modulation of the dc magnetic field can be treated."Rotary saturation" is observed by applying an audio-frequency magnetic field to the sample in the dc field direction while observing the dispersion derivative at resonance with a large rf field H1. When the audio-frequency approaches γH1 the dispersion signal decreases and goes through a minimum. The effect is easily treated theoretically in solids, liquids and gases by using a rotating coordinate system, and is a rotary analogue of ordinary saturation. It is a convenient method for calibrating rf magnetic fields and appears potentially capable of providing useful information on the solid state. Experimental data on rotary saturation are presented and discussed.
Article
While the basic principles of dynamic polarization can be stated in simple terms, a real understanding of the processes that take place between the various systems participating to the phenomenon—namely nuclear spins, electronic spins, lattice vibrations, helium bath, microwave, and radiofrequency fields, requires a knowledge of some aspects of electron and nuclear resonance, such as spin lattice relaxation, spin-spin dynamics, spin temperature in the rotating frame, etc., unfamiliar not only to nuclear physicists but also to many solid-state physicists. This chapter discusses mainly to the only method that has so far yielded practical results in the production of polarized proton targets—namely the so-called “solid effect.” This is the principle of dynamic polarization by dipolar coupling between nuclear and electronic spins; in practical cases, many complications arise. We must mention now that the process that we have just shown to be effective for a pair of neighbouring spins I and S, can be used to polarize a great density of the same nuclei of diamagnetic atoms: this possibility is due to the spin diffusion between nuclear spins.
Article
We present a spin-temperature model, valid at low temperature, of nuclear dynamic polarization using electronic spin systems with g-factor anisotropy and hyperfine structure. Predictions for the maximum polarization corresponding to some free radicals are compared with experiment.
Article
A survey is made of different ways in which nuclear spins can relax through their interaction with electronic spins. It is shown that the maximum amount of nuclear polarization which can be obtained by saturating the electronic resonance depends: (a) on the type of interaction between electronic and nuclear spins, namely dipole-dipole type, scalar product type, or any combination of the two; (b) on the mechanism whereby the "lattice" provides the energy for the relaxation. The case of a nucleus belonging to a paramagnetic ion is examined in some detail with reference to the recent experiment of Honig on arsenic-doped silicon. It is shown that while an Overhauser effect may be expected, this offers no support for an interpretation of Honig's results as a hundred percent nuclear polarization.
Article
The spin-spin relaxation of paramagnetic centres in dielectric solids may act as a cause of nuclear spin relaxation or dynamic polarization, according to the case.
Article
After a general introduction, two sections are devoted to a survey of the theories of spin temperature and of nuclear relaxation in solids. This is followed by a short section on the so-called well-resolved solid effect, and a much more detailed one on DNP by thermal mixing in the non-linear low spin-temperature domain. One then analyses the various methods of measurement of the nuclear polarisation, as well as an indirect method of detecting the electronic resonance based on the existence of large nuclear polarisations. The final section describes briefly several applications of dynamic nuclear polarisation.
Article
We have dynamically polarized the deuterons in deuterated ammonia (ND3) at a temperature of about 200 mK. Maximum vector polarizations of −0.44±0.02 in a magnetic field of 2.5 T and −0.49±0.04 at 3.5 T have been obtained. From these values the deuteron tensor polarization is calculated to be 0.15±0.02 and 0.19±0.03, respectively.
Article
The development, in the early 1960s, of the dynamic nuclear polarization scheme in solid diamagnetic materials, doped with paramagnetic radicals, led to the use of solid polarized H and D targets in numerous nuclear and particle physics experiments. In the 1980s this well established technology was supplemented by the developments of polarized H, D and 3He gas targets, fed by atomic beams or by optically pumped gas. Since then steady progress has been made in all contributing sub-systems so that proton polarization values around 90% and deuteron as well as 3He polarization values between 40% and 85% have been routinely achieved in various setups. These polarization values have been measured with a relative accuracy of ±5% or better using nuclear magnetic resonance techniques and other improved polarimetry methods. Many experiments with reasonably high luminosities have taken advantage of these developments and many more are being planned, especially with electromagnetic probes.
Article
Samples of 7LiH, 6LiD, 6LiH have been irradiated at the Bonn 20 MeV electron preaccelerator under various temperatures and with different radiation doses. The most important paramagnetic defect, the so-called F-center, created during these irradiations has been studied in a conventional EPR spectrometer at liquid nitrogen temperature. Also several samples have been dynamically polarized in both a 4He evaporation cryostat (1 K) and in a dilution refrigerator (200 mK) at a magnetic field of 2.5 and 5 T. Finally some selected samples have been exposed to an intense (up to 70 nA) and high energy (1.2 GeV) electron beam at the Bonn Electron Stretcher and Accelerator ELSA.
Article
Dynamic proton polarizations around 40% have been reproducibly obtained in 5 cm3 samples made of 95% 1-butanol and 5% water mixtures, saturated with the free radical porphyrexide, at temperatures close to 1°K in a magnetic field of 25 kOe.
Article
Polarizations exceeding 70 % have been obtained in a sample of 6LiD, for the nuclear spins of lithium and deuterium. These results make 6LiD a polarized target material which outperforms all other materials tried so far. Des polarisations supérieures à 70 % ont été obtenues dans un échantillon de deutériure de lithium 6LiD pour les spins nucléaires de lithium et de deutérium. Ces résultats font de 6LiD un matériau de cible polarisée dont les performances excèdent considérablement celles de tous les autres matériaux étudiés à ce jour.