Hyperpolarising 13C for NMR studies using laser-polarised 129Xe: SPINOE vs thermal mixing

doi:10.1016/S0009-2614(03)00318-X

Chemical Physics Letters

Volume 371, Issues 5–6, 14 April 2003, Pages 640-644

https://doi.org/10.1016/S0009-2614(03)00318-X Get rights and content

Abstract

We have compared the efficiency of spin polarisation-induced nuclear Overhauser effect (SPINOE) and low-field thermal mixing (TM) for enhancing the $^{13} C$ NMR signal by polarisation transfer from hyperpolarised xenon. In our experiments of TM, the carbon NMR signal was increased by up to a factor of 390, about five times larger than the maximum enhancement obtained using SPINOE in liquid hyperpolarised xenon. Moreover, we show that the enhanced $^{13} C$ nuclear polarisation survives a solid/liquid transition, and the subsequent separation of the carbon compound from hyperpolarised xenon, thus opening the possibility of producing hyperpolarised carbon compounds for NMR applications in biological systems and materials science.

Introduction

Due to its omnipresence in biological and organic materials, and its rich NMR spectrum, $^{13} C$ is the nucleus of choice for many biological NMR spectroscopy studies in vitro. However, the application of carbon NMR imaging and spectroscopy, particularly in living systems, is limited by poor sensitivity, a consequence of the low natural abundance (1.1%) and low gyromagnetic ratio of $^{13} C$ (γ^1H/γ^13C∼4). Using double resonance techniques, the nuclear polarisation of protons can be transferred to attached carbons, resulting in an increase of the $^{13} C$ NMR signal by one order of magnitude. However, for many spectroscopy and imaging applications the low sensitivity of $^{13} C$ remains a severe limitation.

For the noble gases xenon and helium, low sensitivity can be overcome and substantially increased by optical pumping methods. Using these techniques, the nuclear spin polarisation of $^{129} Xe$ and $^{3} He$ can be enhanced by several orders of magnitude, resulting in a dramatic enhancement of the NMR signal (up to a factor of 10⁵). Since the nuclear polarisation created through optical pumping is far from the equilibrium Boltzmann polarisation, these gases are usually referred to as ‘hyperpolarised’ gases.

If $^{13} C$ could be hyperpolarised, its relatively long spin–lattice relaxation times [1] would enable NMR experiments to be performed before the enhanced magnetisation relaxes back to its thermal equilibrium value. However, optical pumping techniques cannot be applied directly to carbon compounds, and different methods, such as parahydrogen induced polarisation (PHIP [2], [3], [4]), or dynamic nuclear polarisation (DNP [5], [6], [7]), have recently been proposed.

As an alternative, the carbon NMR signal can be increased by transferring the enhanced nuclear polarisation of hyperpolarised $^{129} Xe$ to $^{13} C$ with methods like spin polarisation-induced nuclear Overhauser effect (SPINOE) [8], [9] or low-field TM [5], [6], [10].

SPINOE is the result of cross-relaxation between hyperpolarised xenon and other nuclear species in liquid solution. The largest effect has been observed using hyperpolarised liquid xenon as a solvent [9].

TM is driven by the dipolar term of the nuclear Hamiltonian and requires a matrix of uniformly distributed $^{13} C$ in solid $^{129} Xe$ . When the applied magnetic field is lowered to a value comparable to the local dipolar fields, the two nuclear species can reach a common spin temperature, with a net enhancement of carbon magnetisation.

Our aim was to study the $^{13} C$ polarisation enhancements obtainable from hyperpolarised $^{129} Xe$ , and to compare the efficiency of SPINOE and TM for producing hyperpolarised carbon compounds. As a model molecule for this preliminary study, carbon disulphide was chosen due to its good solubility in liquid xenon and its long spin–lattice relaxation times [1], [9].

Section snippets

Materials and methods

Hyperpolarised xenon was produced by optical pumping and spin exchange using the method described by Driehuys et al. [11]. A mixture of 1% $^{129} Xe$ , 1% N₂ and 98% He (Spectra Gases) at 600 kPa flowed through an optical cell heated to 150 °C containing a visible drop of rubidium (Aldrich). The Rb vapour was optically pumped with circularly polarised light from a 90 W diode laser array (Opto Power). After leaving the optical cell, the gas mixture passed through a cold finger at liquid nitrogen

Results and discussion

The observed values of the enhancements obtained from SPINOE range from 40× to 70×, with variations depending on the starting xenon polarisation and Xe/CS₂ molar ratio (range 1–5). Enhancements obtainable from TM were always bigger than those from SPINOE, with an observed maximum at a field $B_{mix} =5 mT$ , where the TM is 4.7 times more efficient than SPINOE. No significant difference was observed in the explored range of mixing time t_mix (1–5 s). The observed maximum is probably a result of two

Conclusion

Enhancements of the $^{13} C$ signal by a factor 390 were obtained by thermal mixing at low field in a xenon–carbon system This was several times more efficient than SPINOE in liquid xenon. We observed that an appropriate choice of experimental parameters is important for production of hyperpolarised $^{13} C$ compounds with this method. We have also shown that the hyperpolarised carbon compound can be separated from xenon while preserving the enhanced nuclear polarisation. Calculation of the theoretical

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Interdependence of in-cell xenon density and temperature during Rb/ <sup>129</sup>Xe spin-exchange optical pumping using VHG-narrowed laser diode arrays
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The high nuclear spin polarization of hyperpolarized (HP) noble gases (e.g. 129Xe, 83Kr, and 3He) can be exploited to increase NMR detection sensitivity by several orders of magnitude, leading to their use in a variety of magnetic resonance applications [1,2], including: biomedical MR imaging and spectroscopy [3–8]; probing pores and surfaces of molecules and materials [9–17]; xenon biosensors [18,19]; and low-field [20,21] and remotely-detected [22] NMR and MRI—as well as experiments where HP gases are employed as nuclear magnetization sources for other species [23–26].
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In this paper, we describe a 250 GHz gyrotron oscillator, a critical component of an integrated system for magic angle spinning (MAS) dynamic nuclear polarization (DNP) experiments at 9 T, corresponding to 380 MHz ¹H frequency. The 250 GHz gyrotron is the first gyro-device designed with the goal of seamless integration with an NMR spectrometer for routine DNP enhanced NMR spectroscopy and has operated under computer control for periods of up to 21 days with a 100% duty cycle. Following a brief historical review of the field, we present studies of the membrane protein bacteriorhodopsin (bR) using DNP enhanced multidimensional NMR. These results include assignment of active site resonances in [U-¹³C, ¹⁵N]-bR and demonstrate the utility of DNP for studies of membrane proteins. Next, we review the theory of gyro-devices from quantum mechanical and classical viewpoints and discuss the unique considerations that apply to gyrotron oscillators designed for DNP experiments. We then characterize the operation of the 250 GHz gyrotron in detail, including its long-term stability and controllability. We have measured the spectral purity of the gyrotron emission using both homodyne and heterodyne techniques. Radiation intensity patterns from the corrugated waveguide that delivers power to the NMR probe were measured using two new techniques to confirm pure mode content: a thermometric approach based on the temperature-dependent color of liquid crystalline media applied to a substrate and imaging with a pyroelectric camera. We next present a detailed study of the mode excitation characteristics of the gyrotron. Exploration of the operating characteristics of several fundamental modes reveals broadband continuous frequency tuning of up to 1.8 GHz as a function of the magnetic field alone, a feature that may be exploited in future tunable gyrotron designs. Oscillation of the 250 GHz gyrotron at the second harmonic of cyclotron resonance begins at extremely low beam currents (as low 12 mA) at frequencies between 320 and 365 GHz, suggesting an efficient route for the generation of even higher frequency radiation. The low starting currents were attributed to an elevated cavity Q, which is confirmed by cavity thermal load measurements. We conclude with an appendix containing a detailed description of the control system that safely automates all aspects of the gyrotron operation.
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The authors discuss several applications for low-field NMR, and suggest that by freezing the solutions and carrying out CP methods to increase the polarization transfer would further increase the signal strength and the applicability. Bifone and coworkers277 have also carried out thermal mixing experiments to transfer xenon polarization to 13C, using 13CS2 as the target species. They also compared thermal mixing to SPINOE and found that low-field thermal mixing could provide enhancements as large as 390 times the Boltzmann polarization at 1.5 T, whereas the SPINOE transfer was about five times less efficient.
This chapter summarizes the recent developments in both convention and hyperpolarized (HP) xenon NMR experiments. Xenon NMR has been used in a growing number of spectroscopy and imaging approaches to physical, chemical, and biological problems. Because of its sensitivity to chemical environment, its inertness, and now the ability to create high polarization through optical pumping xenon has become an extremely useful NMR nucleus to probe an enormous range of materials. Increasingly, we find that unusual materials are being examined with xenon NMR. In addition, more powerful computational methods are now available, making the calculation of xenon chemical shifts possible under a variety of experimentally simulated situations. Approximately half of the papers published over the past 7 years now involve the use of HP xenon because of the dramatic enhancement in sensitivity it affords, and because the optical pumping technology has become more routine. This advance has given rise to a significant increase in the papers that describe the use of 2D methods for xenon NMR as well as static and even dynamic imaging. Some of the rather exotic new methods that have been proposed recently promise to enhance the sensitivity and applicability of xenon NMR experiments well into the future.
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In addition to investigations of the NMR of adsorbed xenon, hyperpolarized xenon has also been used to transfer polarization to surface species. The main methods for this transfer have been low-field thermal mixing [17–19], spin polarization induced nuclear Overhauser effect (SPINOE) [20], and cross-polarization [21,22]. In this study, we demonstrate a relatively simple system that takes advantage of the high polarization of xenon leaving the sample cell to improve the maximum xenon polarization by 3.5 times and thus provides one of the highest xenon polarizations achieved to date.
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Hyperpolarising 13C for NMR studies using laser-polarised 129Xe: SPINOE vs thermal mixing

Abstract

Introduction

Section snippets

Materials and methods

Results and discussion

Conclusion

Prog. Nucl. Magn. Reson. Spectrosc.

Prog. Nucl. Magn. Reson. Spectrosc.

Acad. Radiol.

Chem. Phys. Lett.

Chem. Phys. Lett.

J. Am. Chem. Soc.

Hyperpolarising ¹³C for NMR studies using laser-polarised ¹²⁹Xe: SPINOE vs thermal mixing