Laser-polarized Xenon Research Articles

129Xe ultra-fast Z spectroscopy enables micromolar detection of biosensors on a 1 T benchtop spectrometer.

The availability of a benchtop nuclear magnetic resonance (NMR) spectrometer, of low cost and easily transportable, can allow detection of low quantities of biosensors, provided that hyperpolarized species are used. Here we show that the micromolar threshold can easily be reached by employing laser-polarized xenon and cage molecules reversibly hosting it. Indirect detection of caged xenon is made via chemical exchange, using ultra-fast Z spectroscopy based on spatio-temporal encoding. On this non-dedicated low-field spectrometer, several ideas are proposed to improve the signal.

Multichannel MRI labeling of mammalian cells by switchable nanocarriers for hyperpolarized xenon.

We demonstrate a concept for multichannel MRI cell-labeling using encapsulated laser-polarized xenon. Conceptually different Xe trapping properties of two nanocarriers, namely macrocyclic cages as individual hosts or compartmentalization into nanodroplets, ensure a large chemical shift separation for Xe bound in either of the carriers even after cellular internalization. Two differently labeled mammalian cell populations were imaged by frequency selective saturation transfer resulting in a switchable "two-color" xenon-MRI contrast at micro- to nanomolar Xe carrier concentrations.

Spectral and temporal features of multiple spontaneous NMR-maser emissions

When a system composed of dissolved laser-polarized xenon with negative spin temperature is put inside a high field NMR magnet, a series of spontaneous maser emissions can be observed. We report here their spectral and temporal features using a processing model derived from the solution of the Bloch equations in the presence of radiation damping. We show, in particular, that by combining Fourier transformation and squared modulus, a parameter allowing the characterization of the burst of transverse magnetization can be determined. This parameter is shown to be correlated with the radiated energy. Moreover, this processing clearly reveals features which can probably be assigned to effects resulting from distant dipolar fields. Finally, the analysis of the experimental data reveals an unexpected behavior of the 129 Xe transverse self-relaxation.

Generation of laser-polarized xenon using fiber-coupled laser-diode arrays narrowed with integrated volume holographic gratings

Volume holographic gratings (VHGs) can be exploited to narrow the spectral output of high-power laser-diode arrays (LDAs) by nearly an order of magnitude, permitting more efficient generation of laser-polarized noble gases for various applications. A ∼3-fold improvement in 129Xe nuclear spin polarization, P Xe, (compared to a conventional LDA) was achieved with the VHG-LDA’s center wavelength tuned to a wing of the Rb D 1 line. Additionally, an anomalous dependence of P Xe on the xenon density within the OP cell is reported—including high P Xe values (>10%) at high xenon partial pressures (∼1000 torr).

Sensitivity and Multiplexing Capabilities of MRI Based on Polarized 129Xe Biosensors

129Xe MRI is applied to cage molecules in which hyperpolarized xenon exhibits a specific spectral signature. In a few tens of seconds a net spatial discrimination is achieved between xenon in two different hosts dissolved in two immiscible media at submillimolar concentrations by using a gradient echo sequence with interleaved frequency selection. This high sensitivity is afforded not only by the hyperpolarized state of xenon but also by the continuous xenon in-out exchange that enables replenishment of the detected signal. Moreover in this direct approach, simultaneous detection of xenon in two different cage molecules is possible. This experiment on a model system is an important step toward in vivo multiplexed MRI using laser-polarized xenon.

Cryptophane-Xenon Complexes in Organic Solvents Observed through NMR Spectroscopy

The interaction of xenon with cryptophane derivatives is analyzed by NMR by using either thermal or hyperpolarized noble gas. Twelve hosts differing by their stereochemistry, cavity size, and the nature and the number of the substituents on the aromatic rings have been included in the study, in the aim of extracting some clues for the optimization of (129)Xe-NMR based biosensors derived from these cage molecules. Four important properties have been examined: xenon-host binding constant, in-out exchange rate of the noble gas, chemical shift, and relaxation of caged xenon. This work aims at understanding the main characteristics of the host-guest interaction in order to choose the best candidate for the biosensing approach. Moreover, rationalizing xenon chemical shift as a function of structural parameters would also help for setting up multiplexing applications. Xenon exhibits the highest affinity for the smallest cryptophane, namely cryptophane-111, and a long relaxation time inside it, convenient for conservation of its hyperpolarization. However, very slow in-out xenon exchange could represent a limitation for its future applicability for the biosensing approach, because the replenishment of the cage in laser-polarized xenon, enabling a further gain in sensitivity, cannot be fully exploited.

Effects on 1H and 129Xe NMR spectra of large magnetization created by dissolved laser-polarized xenon

Nous decrivons les principaux effets observes sur les spectres RMN 1 H et 129 Xe quand une grande quantite de xenon fortement polarise par laser est dissoute dans un solvant deutere. Ainsi, la forte polarisation du xenon influe sur l'intensite des signaux des protons du fait de la relaxation dipolaire croisee. De plus, sa grande aimantation volumique cree un champ dipolaire moyen important qui, en se superposant au champ magnetique statique, modifie les frequences de resonance des protons. Enfin la dynamique de spin du xenon s'en trouve modifiee. Cela peut se traduire par un changement de frequence de resonance, par un elargissement de sa raie de resonance, par l'apparition de raies etroites dues a la precession coherente ou encore par de fortes aimantations transversales spontanees (emission maser) quand, par pompage optique, c'est l'etat Zeeman de plus haute energie du xenon qui devient le plus peuple.

Optimization of continuous flow pump cells used for the production of hyperpolarized 129Xe: A theoretical study

Laser-polarized xenon can be used to increase the sensitivity of NMR experiments by 4–5 orders of magnitude, enabling numerous applications in physics, chemistry, biology, and medicine. For the production of hyperpolarized (hp) 129Xe, continuous flow pump cells are commonly used. Based on a 3D numerical model consisting of eight partial differential equations [1], we describe the optimization of continuous flow cells with respect to several experimental parameters in this contribution. We also compare our simulations with data from literature.

Evidence of Specific Interactions between Laser-Polarized Xenon and Arenesulfonic Acid Groups in Functionalized SBA-15 Materials

SBA-15 samples functionalized with different arenesulfonic organic contents and prepared at 373 K were characterized by hyperpolarized 129Xe NMR spectroscopy. Variable-temperature measurements provide information on the organic groups distribution in the materials and on Xe diffusion in the mesopores. The heat of adsorption of xenon on the surface as well as its chemical shift value in interaction with the surface are deduced from the temperature dependence of the 129Xe chemical shift. The arenesulfonic group surface coverage was determined, and consequently, the “organic phase” contribution to the shielding constant was estimated. The evolution of the chemical shift with pressure allowed us to evaluate the “xenon−organic phase” interactions and hence distinguish the different organic contents. The slope of the pressure chemical shift dependence reveals the way in which the functionalization process took place. For low organic content (0.05 and 0.10), the slope is negative, indicating the presence of shallow micropores, while for high organic content (0.15 and 0.20), the chemical shift remains unchanged with the pressure showing that the modified mesoporous surface is homogeneous and micropores exempt. Information about the vicinity of Xe−organic phase are obtained from 129Xe−1H CP and SPINOE experiments.

A Cryptophane Core Optimized for Xenon Encapsulation

The smallest cryptophane ever synthesized, cryptophane-1.1.1 (1), whose internal volume is estimated to be 81 Å3, exhibits the highest binding constant (10000 M-1 at 293 K) in organic solution for xenon encapsulation determined to date. The very slow kinetics of decomplexation on the NMR time scale results in an extremely sharp 129Xe NMR signal for the Xe@1 complex, which shows an unexpected low-frequency shift. The free energy of activation for decomplexation of xenon at 293 K is ΔG⧧out = 64.9 ± 3 kJ mol-1 (ΔH⧧out = 43.2 ± 1.6 kJ mol-1; ΔS⧧out = −74 ± 3 J mol-1 K-1). These properties suggest that the cryptophane core of 1 is optimized for use in sensing applications in combination with laser-polarized xenon.

1H and 129Xe NMR absorption line shapes in the presence of highly polarized and concentrated xenon solutions in high magnetic field

The presence of highly concentrated dissolved laser-polarized xenon (∼1 mol/L, polarization up to 0.2) induces numerous effects on proton and xenon NMR spectra. We show that the proton signal enhancements due to 129Xe– 1H cross-relaxation (SPINOE) and overall shifts of the proton resonances due to the average dipolar shift created by the intense xenon magnetization are correlated. Protons behave as very useful sensors of the xenon magnetization. Indeed the xenon resonances exhibit many features such as superimposition of narrow lines on the main resonance due to clustering effects, or such as a polarization-dependent line broadening that is tentatively assigned to the effects of temperature fluctuations that decorrelate some distant dipolar field effects from local interactions, transforming xenon spins from “like” to “unlike” spins. These spectral features make difficult the determination of the average dipolar field by means of the xenon resonance but have interesting consequences on the heteronuclear polarization transfer experiment in Hartmann–Hahn conditions (SPIDER).

Direct enhancement of any solution NMR signal using the distant dipolar fields created by highly polarized and concentrated nuclear spin systems

Peculiar nuclear spin systems can be polarized at a level of thousands times the value obtained at thermal equilibrium, for instance by optical pumping. When concentrated, these systems create a sizeable average dipolar field which is experienced by any nuclear spin. We propose to use these distant dipolar fields for performing a polarization transfer in the Hartmann-Hahn conditions. We report the maximum enhancement value calculated using the spin temperature approach and first theoretical insights on the polarization transfer rate. Using, as an example, dissolved laser-polarized xenon, we show that by spin-locking both xenon spins and a proton spin of a solute, the polarization of the latter is enhanced. This is obtained without the existence of chemical interaction between the two entities and with characteristic rising time not directly correlated to the proton self-relaxation time. By its generality and its non-local feature, this approach could make possible nuclear magnetic resonance spectroscopy on very dilute systems.

Characterization of violet emission from Rb optical pumping cells used in laser-polarized xenon NMR experiments

Visible emission from Rb optical pumping cells was characterized under a range of conditions relevant to the production of laser-polarized xenon (including temperature, partial pressures, and D 1-resonant 795 nm laser power). Bright 421 nm (6P → 5S) emission was consistent with energy-pooling processes of the type: Rb ∗(5P 1/2) + Rb ∗(5P 1/2,3/2) → Rb ∗(6P 1/2,3/2) + Rb(5S 1/2), with processes transiting through 5D states likely contributing at higher temperatures/lower N 2 partial pressures. Under such conditions a number of Rb lines may be observed, indicating population of Rb states to ⩾9D (∼31 822 cm −1). Such energies exceed those required for efficient production of laser-induced plasma.

Dynamics of Xenon Binding Inside the Hydrophobic Cavity of Pseudo-Wild-type Bacteriophage T4 Lysozyme Explored through Xenon-Based NMR Spectroscopy

Wild-type bacteriophage T4 lysozyme contains a hydrophobic cavity with binding properties that have been extensively studied by X-ray crystallography and NMR. In the present study, the monitoring of 1H chemical shift variations under xenon pressure enables the determination of the noble gas binding constant (K = 60.2 M(-1)). Although the interaction site is highly localized, dipolar cross-relaxation effects between laser-polarized xenon and nearby protons (SPINOE) are rather poor. This is explained by the high value of the xenon-proton dipolar correlation time (0.8 ns), much longer than the previously reported values for xenon in medium-size proteins. This indicates that xenon is highly localized within the protein cavity, as confirmed by the large chemical shift difference between free and bound xenon. The exploitation of the xenon line width variation vs xenon pressure and protein concentration allows the extraction of the exchange correlation time between free and bound xenon. Comparison to the exchange experienced by protein protons indicates that the exchange between the open and closed conformations of T4 lysozyme is not required for xenon binding.

NMR detection using laser-polarized xenon as a dipolar sensor

Hyperpolarized 129Xe can be used as a sensor to indirectly detect NMR spectra of heteronuclei that are neither covalently bound nor necessarily in direct contact with the Xe atoms, but coupled through long-range intermolecular dipole–dipole interactions. To reintroduce long-range dipolar couplings the sample symmetry has to be broken. This can be done either by using an asymmetric sample arrangement, or by breaking the symmetry of the spin magnetization with field gradient pulses. Experiments are performed where only a small fraction of the available 129Xe magnetization is used for each point, so that a single batch of xenon suffices for the point-by-point acquisition of a heteronuclear NMR spectrum. Examples with 1H as the analyte nucleus show that these methods have the potential to obtain spectra with a resolution that is high enough to determine homonuclear J couplings. The applicability of this technique with remote detection is discussed.

Study of gas-fluidization dynamics with laser-polarized 129Xe

We report initial NMR studies of gas dynamics in a particle bed fluidized by laser-polarized xenon (129Xe) gas. We have made preliminary measurements of two important characteristics: gas exchange between the bubble and emulsion phases and the gas velocity distribution in the bed. We used T2* contrast to differentiate the bubble and emulsion phases by choosing solid particles with large magnetic susceptibility. Experimental tests demonstrated that this method was successful in eliminating 129Xe magnetization in the emulsion phase, which enabled us to observe the time dependence of the bubble magnetization. By employing the pulsed field gradient method, we also measured the gas velocity distribution within the bed. These results clearly show the onset of bubbling and can be used to deduce information about gas and particle motion in the fluidized bed.

Dissolution of laser-polarized xenon in benzene

The study of the dissolution of laser-polarized xenon in degassed deuterated benzene is reported. We show that the time evolution of the xenon signal implies that a transient convective process takes place. It is characterized by velocity-encoding magnetic resonance measurements and MRI experiments.

Xenon NMR measurements of permeability and tortuosity in reservoir rocks

In this work we present measurements of permeability, effective porosity and tortuosity on a variety of rock samples using NMR/MRI of thermal and laser-polarized gas. Permeability and effective porosity are measured simultaneously using MRI to monitor the inflow of laser-polarized xenon into the rock core. Tortuosity is determined from measurements of the time-dependent diffusion coefficient using thermal xenon in sealed samples. The initial results from a limited number of rocks indicate inverse correlations between tortuosity and both effective porosity and permeability. Further studies to widen the number of types of rocks studied may eventually aid in explaining the poorly understood connection between permeability and tortuosity of rock cores.

Probing the Hydrophobic Cavity of Lipid Transfer Protein from Nicotiana tabacum through Xenon-Based NMR Spectroscopy

The hydrophobic cavity of Lipid Transfer Protein 1 from Nicotiana tabacum is investigated in detail by NMR using xenon as a spy. The analysis of the (129)Xe chemical shifts and self-relaxation times gives evidence of protein-xenon interaction. Thermodynamics of the binding is characterized through the study of aliphatic (1)H and (13)C chemical shift variation as a function of xenon pressure. The binding constant is evaluated to 75.5 +/- 1.0 M(-1) at 293 K. The location of xenon inside the cavity is deduced from SPINOE experiments. The noble gas appears to occupy four sites, and xenon self-relaxation experiments indicate that it quickly jumps between different sites. The chemical shifts of amide protons and nitrogens also depend on the xenon concentration, either specifically or nonspecifically for atoms at the external surface of the protein. Yet, contrary to aliphatic atoms, they do not correspond to short-range interactions as confirmed by magnetization transfer experiments between laser-polarized xenon and protons in H(2)O. These (15)N chemical shift variations, used in combination with (15)N transverse self-relaxation rates to determine the lower limit of the binding rate, consequently reveal subtle changes in the structure of the protein upon binding.

Development of a Functionalized Xenon Biosensor

NMR-based biosensors that utilize laser-polarized xenon offer potential advantages beyond current sensing technologies. These advantages include the capacity to simultaneously detect multiple analytes, the applicability to in vivo spectroscopy and imaging, and the possibility of "remote" amplified detection. Here, we present a detailed NMR characterization of the binding of a biotin-derivatized caged-xenon sensor to avidin. Binding of "functionalized" xenon to avidin leads to a change in the chemical shift of the encapsulated xenon in addition to a broadening of the resonance, both of which serve as NMR markers of ligand-target interaction. A control experiment in which the biotin-binding site of avidin was blocked with native biotin showed no such spectral changes, confirming that only specific binding, rather than nonspecific contact, between avidin and functionalized xenon leads to the effects on the xenon NMR spectrum. The exchange rate of xenon (between solution and cage) and the xenon spin-lattice relaxation rate were not changed significantly upon binding. We describe two methods for enhancing the signal from functionalized xenon by exploiting the laser-polarized xenon magnetization reservoir. We also show that the xenon chemical shifts are distinct for xenon encapsulated in different diastereomeric cage molecules. This demonstrates the potential for tuning the encapsulated xenon chemical shift, which is a key requirement for being able to multiplex the biosensor.