A compact X-Band resonator for DNP-enhanced Fast-Field-Cycling NMR

Journal of Magnetic Resonance 271 (2016) 7–14

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A compact X-Band resonator for DNP-enhanced Fast-Field-Cycling NMR Oliver Neudert ⇑, Carlos Mattea, Siegfried Stapf Institute of Physics, Ilmenau University of Technology, D-98693 Ilmenau, Germany

a r t i c l e

i n f o

Article history: Received 4 February 2016 Revised 5 August 2016 Accepted 6 August 2016 Available online 06 August 2016 Keywords: NMR DNP NMRD FFC Relaxometry Relaxation dispersion Hyperpolarization Field cycling Microwave resonator

a b s t r a c t A new probehead was developed enabling Dynamic Nuclear Polarization (DNP)-enhanced Fast-FieldCycling relaxometry at 340 mT polarization field strength. It is based on a dielectric cavity resonator operating in the TM110 mode at 9.5 GHz, which is suitable for both transverse and axial magnet geometries with a bore access of at least 20 mm. The probehead includes a planar radio frequency coil for NMR detection and is compatible with standard 3 mm NMR tubes. The resonator was assessed in terms of the microwave conversion factor and microwave-induced sample heating effects. Due to the compact size of the cavity, appreciable microwave magnetic field strengths were observed even with only moderate quality factors. Exemplary DNP experiments at 9.5 GHz and 2.0 GHz microwave frequency are compared for three different viscous samples, demonstrating the advantage of DNP at 9.5 GHz for such systems. This new probehead enables new applications of DNP-enhanced Fast-Field-Cycling relaxometry of viscous and solid systems. Ó 2016 Elsevier Inc. All rights reserved.

1. Introduction Nuclear spin relaxometry is a well-established experimental technique providing information about molecular dynamics on a microscopic level with applications in various fields, like materials science [1], electrochemistry [2,3], biophysics [4,5], medical chemistry and medicine [6,7]. Measurements of the nuclear spin-lattice relaxation time T 1 at many field strengths allow for a spectral characterization of molecular motions over a broad range of frequencies. Hence, they provide a particularly rich source of dynamic information covering motional time scales between around 100 ps and 100 ls. These measurements usually involve a cyclic variation of the magnetic field, which can be realized either by moving the sample between positions of different magnetic field strength [8,9] or by switching the current of an electromagnet [10,11]. While mechanic shuttle approaches provide high maximum magnetic field strengths, good sensitivity and spectral resolution, they are limited to relaxation times T 1 > 100 ms due to the finite shuttling interval needed to move the sample between the two positions. On the other hand, Fast-Field-Cycling (FFC) NMR, which employs fast electronic switching of the magnet current, provides switching times as short as a few ms, extending the measurable relaxation range to T 1 > 1 ms. However, the strong

⇑ Corresponding author. E-mail address: [email protected] (O. Neudert). http://dx.doi.org/10.1016/j.jmr.2016.08.002 1090-7807/Ó 2016 Elsevier Inc. All rights reserved.

electrical current required in the electromagnets to reach high values of magnetic field strength limits the achievable nuclear spin polarization and detection frequency and thereby the sensitivity of the method. Furthermore, the limited stability and homogeneity of the acquisition field usually prohibits spectrally resolved detection of the free induction decay (FID) signal. In many systems the lack of spectral resolution leads to an overlap of different signal contributions, which cannot be separated straightforwardly and may complicate the interpretation of 1H relaxation data in systems with multiple components. Dynamic Nuclear Polarization (DNP) is a technique that uses the thermal equilibrium polarization of unpaired electron spins to create a considerably increased, non-equilibrium polarization of nuclear spins [12]. For this purpose, the samples are either doped with a stable radical or they contain naturally occurring paramagnetic centers. The hyperpolarized nuclear spin state is achieved through a polarization transfer that occurs when a coupled electron-nuclear spin system is irradiated approximately at the electron spin Larmor frequency, resulting in an increase of the NMR signal amplitude by up to two orders of magnitude. The efficiency of the polarization transfer strongly depends on the modulation of the electron-nuclear spin coupling by molecular motions. When the associated motional correlation times are on the order of the inverse electron spin Larmor frequency, the polarization transfer occurs via the Overhauser effect [13,14]. Under this condition, maximum signal enhancements are obtained when the microwave

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frequency matches the electron spin Larmor frequency. This effect is often accompanied by a phase inversion of the NMR signal, i.e. negative NMR signal enhancements. For longer motional correlation times, however, this effect becomes less effective. On the other hand, solid state DNP effects arise when the molecular motions become so slow that the electron-nuclear spin couplings are not completely averaged out on the time scale of the nuclear spin Larmor frequency. For monoradicals in low or moderate concentration, the solid effect [15–17] can be observed, causing maximum NMR signal enhancements with inverted or non-inverted NMR signal phase when the microwave frequency matches, respectively, the sum or difference of the electron and nuclear spin Larmor frequency. This effect, however, requires that the homogeneous linewidth of the electron paramagnetic resonance (EPR) transitions and the inhomogeneous spectral width are smaller than the nuclear spin Larmor frequency. If this condition is not fulfilled, positive and negative DNP signal enhancements will compensate each other, reducing the overall DNP enhancement [18]. Among other methods for nuclear spin hyperpolarization, such as parahydrogen-induced polarization [19] or the laser-driven polarization of noble gases [20], DNP is a particularly versatile technique that has been applied in liquid [21,22], viscous [23,24] and solid [25,26] systems, at both cryogenic [25–27] and room temperatures [21,22,24,28] and at low [21] and high [22,25,27,28] magnetic field strengths. In the last two decades, technical and methodical developments have brought up outstanding applications of DNP, for example for in vivo magnetic resonance imaging [29] or for MAS NMR spectroscopy [27]. For this purpose DNP experiments usually employ double-resonant structures that create the necessary microwave (MW) and radio frequency (RF) magnetic fields, which need to be perpendicular to the external magnetic field. Commonly employed designs at XBand frequencies (8 GHz. . .12 GHz) are cavity resonators operating in the TE102 [30–32], TE011 [33] or TM110 [34] modes, as well as dielectric resonators operating in the TE011 mode [35,36]. Polymeric cavity insets made of Polystyrene [33] or PTFE [34] have been used to reduce the outer cavity diameter to about 40 mm. However, to our knowledge, no X-Band DNP probehead has been developed that is small enough to be compatible with magnet bore diameters as small as 20 mm. The purpose of the work presented herein was to improve the performance of in-situ DNP-enhanced FFC relaxometry [37] by using X-Band MW frequencies. For this purpose, a new probehead had to be developed, which creates a homogeneous and transverse MW magnetic field at the desired frequency and can be integrated into our FFC relaxometer, having a magnet bore diameter of 20 mm. Further requirements are a sufficiently large sample size, a good NMR detection sensitivity and small MW sample heating effects. In comparison to previous work [37,38] where S-Band frequencies were employed, two substantial improvements are expected from the new system: First, the overall electron and nuclear spin polarization at the given polarization field strength increases by a factor of 5, accordingly increasing the NMR sensitivity. Second, larger DNP enhancements may be obtained in viscous and solid systems when the solid effect is the dominating mechanism, e.g. in polymer melts with BDPA radical [24,37]. Usually, solid effect DNP enhancements are expected to be larger at low magnetic field strengths [12]. However, the EPR spectrum of many radicals is broadened by magnetic field strength-independent hyperfine interactions. Hence, the general condition for the solid effect that the inhomogeneous spectral width must be smaller than the nuclear spin Larmor frequency is violated at low magnetic field strengths. The new probehead is based on a cavity resonator, which operates in the TM110 mode at 9.5 GHz. A high-dielectric constant inset was used to achieve inner and outer cavity diameters of 12.8 mm

and 19 mm, respectively. An RF coil with planar shape was integrated inside the cavity to achieve both an acceptable filling factor and optimum decoupling of the MW and RF electromagnetic fields. The necessary presence of paramagnetic centers for DNP can introduce considerable additional relaxation pathways by electronnuclear spin interactions. However, such a contribution may be minimized by employing small radical concentrations or it may be quantified by varying the radical concentration. On the other hand, paramagnetic relaxation pathways may as well be the object of investigation [39–41]. Since NMR relaxometry is inherently temperature-dependent, several evaluation experiments have been performed to investigate the dynamics and magnitude of MW-induced sample heating effects and efficiency of forced-air cooling. Further evaluations involve the MW conversion factor, the sensitivity of NMR detection and a comparison of nuclear magnetic relaxation dispersion (NMRD) profiles obtained with the DNP probehead and with the standard probehead delivered with the FFC relaxometer for two reference samples. Moreover, DNP enhancements at 2 GHz and 10 GHz MW frequency are compared for three exemplary viscous samples.

2. Materials and methods Samples were contained either in 2.5 mm inner diameter (i.d.), 3.0 mm outer diameter (o.d.) borosilicate glass tubes (3 mm Economy NMR Tubes, Wilmad-LabGlass, Vineland, New Jersey, U.S.A.) or in 1.0 mm i.d., 1.5 mm o.d. capillary tubes (ringcaps 50 ll, Hirschmann Laborgeräte GmbH & Co. KG, Eberstadt, Germany). TEMPO (2,2,6,6-Tetramethyl-1-piperidinyloxyl), 4-HydroxyTEMPO and BDPA (a,c-Bisdiphenylene-b-phenylallyl) radicals were obtained from Sigma-Aldrich (Sigma-Aldrich Chemie GmbH, Taufkirchen, Germany). Trityl OX063 was obtained from Oxford Instruments (Tubney Woods, Abingdon, UK). The crude oil sample was provided by Schlumberger-Doll Research. All samples had a filling height of 10 mm, giving a sample volume of about 50 ll and 8 ll in 2.5 mm i.d. and 1.0 mm i.d. tubes, respectively. The sample temperature was adjusted using a temperaturecontrolled flow of dry air at a flow rate of 11 l/min and temperature calibration was done using a thermocouple immersed in water inside a sample tube with 10 mm filling height. Measurements were performed using a commercial FFC relaxometer (Spinmaster FFC2000, Stelar s.r.l., Pavia, Italy). An X-Band MW setup was implemented for the measurement of reflection coefficients and for providing an amplified MW signal. A block diagram of the setup is shown in Fig. 1c. The two remote-controlled relay switches operate in parallel and are addressed by the TTL output of the field cycling relaxometer. When the relays are switched on, an amplified signal of up to 11 W power is sent to the probehead. Otherwise the resonator is driven by a non-amplified MW signal of up to 6 mW. If not mentioned otherwise, all measurements were performed with a standard pre-polarized FFC sequence (Fig. 1d) which consists of a polarization interval of length tpol with the magnetic field strength set to Bpol , a relaxation interval trlx at Brlx and a detection interval at Bacq . For DNP experiments, the MW resonator is critically coupled and the relays are switched on during tpol . Bpol is adjusted according to the DNP mechanism and radical employed, either driving allowed electron spin transitions (Overhauser effect) or zero/double quantum electronnuclear spin transitions (solid effect). For measurements of the DNP enhancement, the relaxation interval trlx is omitted. NMR signals were acquired at an acquisition field of Bacq ¼ 392 mT using either an FID experiment with a 90° pulse length of 4.8 ls and a pulse-acquisition delay of 16.3 ls, or a spin echo sequence with an echo time of 69.6 ls or a CPMG sequence

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Fig. 1. (a) Exploded-view drawing of the main parts of the X-Band DNP probehead. The labels 1–8 are explained in the text. (b) Simulated magnetic flux density distribution at a MW power of 1 W and Q = 700 showing a cut along the central axis of the resonator. The simulated sample volume with 2.5 mm i.d. and 9 mm length is indicated by the white rectangle in the center. The orientation is the same as in (a). (c) Schematic drawing of the microwave setup. (d) Pre-polarized FFC sequence with microwave irradiation that was used for most of the experiments presented here.

[42,43] with an echo time of 49.6 ls, recording only the peak of each echo to compensate signal dephasing due to magnetic field instabilities [44]. Reference measurements using the standard probehead delivered with the FFC relaxometer (‘‘STELAR probehead”) used the same pulse sequences and acquisition parameters, however with a 90° pulse length of 8.0 ls and echo times of 76 ls and 56 ls for spin echo and CPMG, respectively. For all experiments 180° pulses had twice the length of 90° pulses. The homogeneity of the acquisition field is about 100 ppm over a sample volume of 1 cm3 with the STELAR probehead [45]. Larger field inhomogeneities were observed with the DNP probehead (see below). DNP enhancements were calculated by dividing the integrated signal intensities obtained with and without MW irradiation with otherwise identical experimental parameters. 3. Hardware The MW resonator (Fig. 1a) operates at 9.5 GHz in the TM110 mode, creating a homogeneous, transverse microwave magnetic field of maximum strength across the sample volume, where the electric field strength is minimal. The resonator consists of the following parts: Part 1 is made of Polychlorotrifluoroethylene (PCTFE) and incorporates a precisely machined bore guiding the MW coaxial cable (part 8), a semicircle-shaped notch for guiding the RF coil wire and a central bore for the sample tube. Part 2 is made of copper, provides a mechanical connection to the remaining structure of the probehead (not shown) and serves as the top cap of the cylindrical cavity structure. Part 3 is machined from 99.5% aluminum oxide (ceratec GmbH, Kreutal-Kredenbach, Germany), has an outer diameter of 12.8 mm and a total height of 10.95 mm. The dielectric constant eð9:5 GHzÞ  9:4 of this material enables the compact design of the resonator needed for the 20 mm magnet bore of the FFC relaxometer. The aluminum oxide material exhibits a very small dielectric loss tangent of 9  105 at 9.5 GHz. The four linearly aligned small bores in part 3 allow for insertion of the RF coil copper wires (depicted by cylindrical rods). The copper ring (part 4) serves as the outer shield of the cylindrical resonator,

has a wall thickness of 3.5 mm and contains a slit to avoid eddy currents induced by magnetic field switching. The four bores in part 3 and the slit in part 4 are placed within the plane of vanishing electric field of the TM110 mode, defining its orientation. The bottom cap of the resonator (part 5) is made of copper. Part 6 is made of PCTFE and contains two semicircle-shaped notches at the bottom to guide the RF wire (not shown). Part 7 is used to attach a flexible hose, connecting the probehead to the temperaturecontrolled air flow. Coupling to the MW electric field is achieved by inserting a short stub at the end of a non-magnetic RG405 semi-rigid coaxial cable (part 8) into the protruding cylindrical structure on the top of part 3, which contains a bore of 0.9 mm diameter and 3 mm depth. The RF coil is made of a 0.28 mm diameter enameled copper wire, which is guided through the cylindrical bores in parts 1, 2, 3, 5 and 6, creating an approximately rectangular-shaped planar RF coil which consists of 3 windings of larger circumference and 3 windings of smaller circumference. Since the RF coil is located in the plane of vanishing electric field of the TM110 mode, the RF and MW electromagnetic fields are decoupled while at the same time an acceptable filling factor is achieved for the RF coil. High-Q, high-voltage and non-magnetic chip capacitors are connected to the RF coil and are placed directly above the resonator shown in Fig. 1a for frequency tuning. Fine tuning and matching is achieved by a matching circuit located outside the magnet, which is connected to the coil and main tuning capacitors via a non-magnetic RG405 coaxial cable (not shown). The dead-time of the probe is 16 ls and FID measurements with more than 6000 repetitions indicated no spurious 1H signal that might be obtained from the insulating enamel of the RF wire. 4. Probehead evaluation and DNP measurements The MW resonator performance was evaluated in terms of the quality factor, the conversion factor, and the MW-induced sample heating effects. Quality factors Q ¼ f 0 =Df were obtained from reflection coefficient measurements of the critically coupled resonator, where f 0 is the resonance frequency and Df is the width

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of the resonator dip at 3 dB. The results are given in Fig. 2a. While for the empty resonator Q unloaded  700 was observed, a significantly lower quality factor of 470 was measured when the resonator was loaded with an empty glass tube or with a benzene sample, which has a vanishing dielectric loss factor. Hence, additional power losses arise from the borosilicate glass material of the sample tube, which has a non-negligible dielectric loss factor at 10 GHz [46,47]. All other quality factor measurements were referenced to this value in order to obtain the relative fraction of MW power dissipated in the sample volume, which can be calculated from [48].

f sample ¼

1=Q sample  1=Q glass ¼ 1  Q sample =Q glass 1=Q sample

where Q sample is the quality factor measured with a given sample in a glass tube and Q glass is the quality factor obtained with the empty glass tube. Hence, in the steady state, an additional power loss equal to f sample  P MW needs to be dissipated in the filled sample tube, leading to an increase in sample temperature D# that is proportional to both f sample and the microwave power P MW . In general all measured quality factors are comparatively low. Other TM110 resonators used for electron-nuclear double resonance (ENDOR) experiments at X-Band [34,49–51] were reported, having significantly higher values of Q unloaded between 1800 [51] and 9500 [49]. This discrepancy is probably caused by the fact that we did not employ silver or gold coating of the conductive cavity parts, leading to the formation of a copper oxide layer that causes additional resistive losses in the cavity walls. However, for sample volumes of 50 ll, sample dielectric losses dominate the quality factor in most cases (Fig. 2a). Such sample volumes are preferred in order to avoid unnecessary compromises considering the signal intensity in comparison to standard FFC applications, which typically use a sample volume of 500 ll. Therefore, in many practical applications of XBand DNP-enhanced FFC the moderate quality factor will not be a large disadvantage. The conversion factor of the MW resonator was evaluated using finite-element (FEM) simulations [52] on the one hand and by comparison of power-dependent DNP enhancements with a wellcharacterized ENDOR probehead (EN4118X-MD4, Bruker Biospin, Rheinstetten, Germany) on the other hand. The FEM evaluation is based on a simulation of the TM110 eigenmode, incorporating dielectric losses inside the Al2O3 material, resistive losses inside the copper parts and radiation losses arising from electromagnetic leakage through openings of the cavity. The average microwave magnetic field strength B1 was calculated from the simulated

magnetic flux density distribution (Fig. 1b) for a cylindrical sample volume of 2.5 mm diameter and 9 mm height in the center of the cavity. The total power loss was calculated from

Ploss ¼ 2pf r

Eem Q sim

where f r is the resonance frequency of the TM110 mode, Eem is the temporal mean of the total electromagnetic energy and Q sim is the quality factor determined in the simulation. Very large quality factors Q sim  10; 000 were obtained in comparison to the measured value Q unloaded , reflecting the presence of additional losses not incorporated in the simulation. The applied microwave power P, which in the steady state is equal to P loss , is related to B1 by

B1 2 ¼ c2 Q P Accordingly, the conversion factor was calculated as follows:

csim

sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi B1 2 ; ¼ Q sim Ploss

pffiffiffiffiffi giving a value of csim ¼ 0:077 G= W. Hence, average magnetic flux densities of 0.7 G, 1.7 G and 2.0 G are obtained at a MW power of 1 W for quality factors of 80, 470 and 700, respectively. For the commercial ENDOR probehead and aqueous samples, Türke et al. [53] determined MW magnetic flux densities between 1.8 G (sample: 0.9 mm i.d., 10 mm length) and 2.2 G (sample: 0.45 mm i.d., 3 mm length). The latter value was obtained in the case where no significant dielectric losses due to the sample could pffiffiffiffiffi be measured. A normalized MW magnetic flux density of 1 G= W at Q ¼ 150, corresponding to a conversion factor of about pffiffiffiffiffi cENDOR ¼ 0:08 G= W, is specified by the manufacturer [54]. A comparison of MW power-dependent DNP enhancements in airsaturated solutions of 20 mmol/l TEMPO radical in benzene at +20 °C is shown in Fig. 2b (squares), measured with the ENDOR probehead (sample: 2.0 mm i.d., 4 mm length) [55] and the new probehead (sample: 2.5 mm i.d., 10 mm length). The overlap of the data indicates that essentially the same MW magnetic field pffiffiffiffiffi strengths of around 2 G= W are obtained from the ENDOR and the new probehead. Large DNP enhancements are obtained from both probeheads as a result of the relatively large radical concentration promoting electron spin exchange effects, which allow for effective saturation of more than one hyperfine transition of the nitroxide radical. Surprisingly, the comparison of both probeheads suggests an even larger conversion factor than the one obtained from the simulation. However, they are considered to be approxi-

Fig. 2. (a) Steady-state microwave-induced sample heating coefficients D#=P for different samples plotted against the fraction of microwave power dissipated in the sample volume (f sample ). The sample i.d. was 1.0 mm for the water sample (circle) and 2.5 mm for all other samples (squares). (b) 1H DNP enhancements obtained for an air-saturated solution of 20 mmol/l TEMPO in benzene (filled symbols) and 4-Hydroxy-TEMPO in water (open symbols), using a commercial ENDOR resonator (Bruker EN4118X-MD4) operating at 9.7 GHz (squares) [55,56] and the new X-Band DNP probehead (triangles).

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mately in agreement with the simulation, considering the uncertainty of the quality factor determination and the different sample sizes. Furthermore, a comparison of DNP-enhancements for aqueous solutions of 20 mmol/l 4-Hydroxy-TEMPO radical is shown in Fig. 2b (triangles), which were measured with the ENDOR probehead (sample: 1.0 mm i.d., 4 mm length) [56] and the new probehead (sample: 1.0 mm i.d., 10 mm length). These results indicate a 4-times smaller power saturation efficiency despite the moderate quality factor of 360 (Fig. 2a). This discrepancy can be explained by taking into account the much smaller EPR linewidth of the aqueous samples as compared to the air-saturated benzene sample, which is a result of the smaller oxygen concentration in airsaturated aqueous solutions. With the current FFC relaxometer, the precision of the polarization field setting is limited to minimum steps of about 6 kHz 1H Larmor frequency, which causes an electron spin resonance offset of about 2 MHz that reduces the saturation efficiency especially for narrow linewidth-samples. Kay et al. [51] reported a conversion factor for their TM110 ENDOR probehead that corresponds to a MW magnetic flux density of pffiffiffiffiffi 0:87 G= W. This result is significantly smaller than the value reported here, even though a larger quality factor was in their case. The difference can be explained by the larger size of their cavity, which incorporates a 10-times greater volume. Therefore, even though our resonator provides only moderate quality factors, satisfactory MW conversion factors are obtained owing to the small cavity volume. Further improvements can be expected from optimizations increasing the quality factor. Since the resonator is intended for DNP-enhanced FFC relaxometry applications, measuring inherently temperature-dependent nuclear spin relaxation times, MW-induced sample heating effects were evaluated. Heating effect measurements were based on the temperature dependence of the nuclear spin-lattice relaxation time T 1 ð#Þ of nitroxide radical-doped solvents [57]. In a first step, T 1 ð#Þ was measured for each sample between +20 °C and +50 °C without MW irradiation. The steady-state sample heating coefficient D#=P was then obtained from relaxation measurements T 1 ðPÞ under continuous MW irradiation by comparison with the calibration results. Heating measurements were performed for 50 ll samples of different solvents in 2.5 mm i.d., 3.0 mm o.d. glass tubes. Plotting D#=P vs. f sample for those samples (Fig. 2a, squares) approximately confirms the expected linear relationship. With the given sample geometry the heating coefficient extrapolates to +27 K/W when 100% of the MW power is absorbed by the sample. An additional heating measurement was performed for nitroxide radical-doped water (Fig. 2a, circle). Due to the large dielectric loss factor at 9.5 GHz, no resonant mode was observed with a 2.5 mm i. d. sample. Instead, a melt-sealed 1.0 mm i.d., 1.5 mm o.d. capillary was used, providing a sample volume of 8 ll. The 1.0 mm capillary was contained in a 1.7 mm i.d., 2.3 mm o.d. guiding capillary inside a 2.5 mm i.d. glass tube to achieve an accurate placement inside the cavity. Even though the quality factor of 360 indicates only moderate power losses inside the sample, a large steady-state heating effect of 42 K/W was observed. In comparison, about 25 K/W was observed by Doll et al. [58] at X-Band for a 2 ll sample of water contained in a 0.5 mm i.d., 0.89 mm o.d. capillary. When the sample dominates the power losses inside the cavity, the steady-state heating coefficient is only determined by the resistance of the thermal contact between the air flow and the sample volume. This is demonstrated by the much lower heating coefficient of 4 K/W measured by Franck et al. [57] for a 0.6 mm i.d., 0.84 mm o.d. quartz tube after optimizing the cooling air flow in their DNP probehead. The large heating effect observed in our case is probably due to the thermal insulation created by the large total thickness of glass tubes separating the cooling air flow and the sample. Therefore, microwave heating of aqueous samples in

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0.9 mm i.d. capillaries may be reduced significantly in future applications by optimizing the sample geometry and cooling air flow. Even smaller heating effects of about 1 K/W were obtained for a 50 ll sample of water in a previous study at 2 GHz [38] owing to the better magnetic and electric field separation as well as the lower dielectric loss tangent of water at this frequency. The spatial separation of alternating magnetic and electric fields is ultimately limited by the vacuum wavelength of the radiation. Therefore, resonators operating at a lower frequency can achieve a better spatial separation for a given sample geometry. Similarly small heating effects have been observed at X- [53,58] and W-Band [59] frequencies, however for much smaller sample volumes. This suggest SBand DNP as the more suitable alternative for reducing heating effects in DNP-enhanced FFC studies on aqueous systems while retaining an acceptable sample size. The dynamics of the MW-induced sample heating was studied for all above-mentioned samples by applying MW pulses of variable duration t and power P, measuring T 1 ðt; PÞ immediately after the pulse and comparing the results with the calibration T 1 ð#Þ. All samples show similar normalized heating dynamics characterized by an exponential saturation behavior with a time constant of about 5 s. The cooling behavior was studied for one sample by adding a variable delay between the end of the MW pulse and the start of the measurement. The cooling process exhibits a time constant similar to that of the heating process, indicating complete cooling to the environmental temperature after about 30 s. Knowing the steady-state heating effects as well as the irradiation-time dependence and cooling behavior allows one to design DNP-enhanced FFC relaxometry experiments in a way that MW-induced heating effects may either be neglected or compensated by reducing the temperature of the cooling air flow accordingly. Due to the restricted available space inside the magnet bore, a sample dewar could not be included in the probehead. Therefore it was necessary to evaluate possible temperature gradients inside the sample. This was done by positioning a naked-bead thermocouple at several points inside a water sample with 2.5 mm i.d. and filling height 10 mm. A relatively large air flow temperature of +60 °C, corresponding to the maximum sample temperature that can be achieved with the present construction, was chosen in order to obtain an upper estimate for temperature gradients. At flow rates of 7 l/min the temperature difference between the uppermost and lowermost measurement points at 1 mm and 9 mm, respectively, was as large as 4.8 K. However, by using a larger flow rate of 11 l/min this difference was reduced to about 2.1 K. Even smaller temperature gradients are expected for sample temperatures closer to the temperature of the probehead’s environment inside the magnet bore, which is at about +16 °C. Hence, temperature gradients may be considered negligible within a temperature range of about 0 °C . . . +60 °C. The NMR sensitivity of the new DNP probehead was evaluated in comparison to the probehead supplied by the manufacturer of the FFC relaxometer (‘‘STELAR probe”). Three different acquisition schemes were tested: an FID experiment, a spin echo experiment and a CPMG experiment acquiring one point at the peak of each echo. The experiments were performed with a 50 ll sample of water with 25 mmol/l CuSO4, a polarization field strength of 0.47 T and identical acquisition parameters. Each experiment was repeated 64 times in order to assess the reproducibility of the NMR signal intensity. A representative set of data, showing magnitude signal traces sðtÞ obtained after 4 scans, is shown in Fig. 3a and b for the DNP and STELAR probehead, respectively. In all experiments, similar signal amplitudes were observed. However, the FID and spin echo signals decay much faster in the DNP probehead. The same fast decay was observed when the field strengths for the polarization and acquisition field were equal,

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Fig. 3. (a) Magnitude signal traces obtained from thermal-polarized measurements using the X-Band DNP probehead and different pulse sequences. (b) Magnitude signal traces obtained from thermal-polarized measurements using the standard probehead of the FFC relaxometer (‘‘STELAR probe”) and different pulse sequences. (c) Signal-tonoise ratio of the integrated signal calculated from 64 repetitions of the respective experiment and plotted against the total duration of the detection interval. Gray symbols show results obtained with the standard probehead, black points show results obtained with the DNP probehead. (d) Comparison of NMRD profiles measured using the CPMG pulse sequence with the DNP probehead (filled squares and circles), using FID acquisition with the standard probehead (lines) and literature data (open circles) [62] for a sample of poly(dimethylsiloxane) (PDMS) 423 kDa (red line and circles) and a sample of 2 mM MnCl2 in H2O (black line and squares). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

hence avoiding any field jump between the polarization and acquisition periods. Therefore, the fast signal decay cannot be the result of eddy currents induced in the conductive parts of the DNP probehead, which might cause magnetic field strength variations after field switching. The fast decay of the FID and echo signals measured with the DNP probehead rather reveal a disturbance of the magnetic field homogeneity. Furthermore, random fluctuations of the acquisition field strength inherent to the relaxometer, a wellknown technical limitation of FFC NMR [44,60,61], cause additional losses of phase coherence and irreproducible variations of signal intensity in both probeheads, especially for times t > 100 ls. Nevertheless, these drawbacks can be overcome by using the CPMG pulse sequence. For both probeheads, the time interval during which the signal can be detected is dramatically increased using CPMG acquisition, allowing for more than 100 ms of signal integration. In order to evaluate the NMR sensitivity of the DNP probehead and different acquisition schemes, the signal-to-noise ratio (SNR) of the integrated magnitude signal was calculated from

SNRðnÞ ¼

SðnÞ

rS ðnÞ

P where SðnÞ ¼ 64 k¼1 Sk ðnÞ=64 denotes the average over the 64 inteP grated signals Sk ðnÞ ¼ nl¼1 sðt l Þ obtained from the magnitude signal traces sðt l Þ obtained after 4 scans. rS ðnÞ denotes the standard deviation of the integrated signals. Fig. 3c shows the results SNRðnÞ for the different acquisition schemes and probeheads plotted against the overall duration t n of the acquisition interval. Both probeheads provide similar single-point SNRs between 20 and 30. The

maximum achievable SNR from FID measurements, however, is limited for the DNP probehead due to the fast signal decay. This deficit is mostly compensated by employing spin echo acquisition, giving an SNR of about 90. For samples with a sufficiently long spin-spin relaxation time T 2 P 2 ms the best SNR can be obtained from CPMG acquisition, providing a 3-fold increase in SNR over spin echo acquisition for this sample and the DNP probehead. Considering the technical limitations of including an RF coil inside a small cavity resonator, which needs to be decoupled from the MW mode, satisfactory NMR sensitivity is obtained from the DNP probehead, giving similar results as the commercial STELAR probehead. As a test for the reliability of FFC relaxometry data measured with the DNP probehead, nuclear magnetic relaxation dispersion profiles (NMRD profiles) of two common reference sample were recorded using CPMG acquisition and compared to data obtained with the STELAR probehead and FID detection (‘‘STELAR”) on the one hand and literature data [62] on the other hand (Fig. 3d). A very good agreement is achieved between the different data sets, demonstrating that accurate relaxation measurements are possible with the DNP probehead over the whole Larmor frequency range of the instrument. The development of an X-Band DNP probehead for FFC NMR may provide advantages over S-Band DNP for viscous samples when the solid effect is the relevant DNP mechanism. Table 1 shows a comparison of maximum DNP enhancements obtained at S- and X-Band MW frequencies for three exemplary viscous samples. Polarization field-dependent DNP measurements, showing positive and negative enhancements at negative and positive electron spin resonance offsets, respectively, have confirmed that

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Table 1 Comparison of maximum DNP enhancements and corresponding MW power for several viscous systems at S-Band (2 GHz) and X-Band (9.5 GHz) MW frequencies. The viscosity literature values refer to pure solvents. Sample

Crude oil (13wt% asphaltene containing radicals) Trityl-OX063 in Glycerine (<20 wt% H2O) BDPA in Polybutadiene 24 kDa

Radical concentr.

2 mM (approx.) [64] 20 mM 4 mM

solid state DNP effects are relevant in these systems. Due to the low radical concentrations, the solid effect is assumed to be the dominating mechanism for the polybutadiene sample with the monoradical BDPA. For this sample a 7-fold increase in the maximum DNP enhancement is observed, which can be explained by the hyperfine couplings to eight equivalent 1H nuclear spins on BDPA. These couplings cause magnetic field strengthindependent EPR line splittings that lead to an inhomogeneous spectral width of about 40 MHz [63]. Hence, at S-Band frequencies positive and negative DNP enhancements compensate each other to a large degree, limiting the overall DNP enhancement [18]. Interestingly, even with the narrow-line width radical Trityl-OX063 a 17-fold increased DNP enhancement is observed at X-Band. These findings suggest that an at least 5-fold improvement in DNP enhancement can be expected for X-Band in viscous systems. However, in order to verify this conclusion more detailed investigations are necessary, regarding potential contributions from other solid state DNP effects, the electron and nuclear spin relaxation rates as well as the EPR line shape. The observation of significant X-Band DNP enhancements in viscous systems at room temperature enables the implementation of new molecular dynamics-selective detection methods. Based on the different polarization-field dependences of liquid and solid state DNP effects, such methods may discriminate DNP-enhanced NMR signals originating from either of the effects. This will allow for a selective detection of molecules that exhibit either fast or slow molecular dynamics with respect to the radical. Such a method, which will be presented in a forthcoming publication, may help to overcome the limited selectivity of FFC relaxation experiments. 5. Conclusions A new probehead was developed for axial magnet geometries with a bore access of 20 mm which enables in-situ DNPenhanced measurements at 9.5 GHz microwave frequency (340 mT polarization field strength). The probehead provides irradiation with transverse MW magnetic fields based on a TM110 mode dielectric cavity resonator and incorporates RF coils decoupled from the MW resonant mode. Using the new probehead an X-Band DNP setup was implemented for use with a commercial electronically-switching electromagnet. Evaluation measurements of the MW resonator indicated only moderate quality factors of up to 700, which may limit the maximum achievable MW magnetic field strength. However, this is compensated by the small size of the resonator, which increases the energy density and thereby improves the MW conversion factor. Accordingly, a satisfactory conversion factor of pffiffiffiffiffi about c  0:08 G= W was obtained, corresponding to a maximum MW magnetic flux density of about 2 G at 1 W microwave power. Still, further improvements are expected from optimizations increasing the quality factor. A satisfactory NMR sensitivity was obtained, providing similar SNRs as the instrument’s standard probehead. The application of CPMG-detected methods was shown to provide a 3-fold increase in SNR, partially compensating the

Viscosity

0.73 P [65] >16 P [66] 1200 P [67]

Temp.

+20 °C 20 °C +25 °C

Maximum enhancement S-Band (73 mT)

X-Band (340 mT)

+2.7 @ 4.3 W +3.4 @1.0 W +2.1 @ 7.1 W

+14.5 @ 3.5 W +57.2 @ 0.8 W +14.3 @ 4.2 W

general drawback of reduced sample volumes for DNP-enhanced versus standard FFC relaxometry. DNP-enhanced measurements were shown to be feasible with sample volumes of up to 50 ll when moderate dielectric losses are present. With such a relatively large sample volume, the evaluation of microwave-induced sample heating effects gave acceptable results similar to those reported by other groups for X-Band DNP [58]. However, comparatively large heating effects were observed for 0.9 mm i.d. water samples owing to a non-optimal sample tube geometry that increases the thermal resistance. Moreover, steady-state heating effects could be correlated to the MW resonator’s quality factor and a study of dynamic heating effects provided guidelines for setting up DNP-enhanced FFC experiments with negligible or partially compensated sample heating. DNP experiments at 9.5 GHz MW frequency were shown to provide considerable signal enhancements for exemplary liquid and viscous samples. Especially for the latter, a significant improvement of the attainable signal enhancement is obtained in comparison to a previously published system for DNP-enhanced FFC operating at 2 GHz MW frequency [37,38]. In addition, the increase of the overall spin polarization provides another 5-fold improvement in sensitivity for the X-Band DNP setup over the S-Band setup. Therefore, the development of an X-Band probehead is an essential extension for DNP-enhanced FFC relaxometry that improves applications in viscous and solid systems and provides further increased sensitivity. At the same time, S-Band DNP is usually best suited for aqueous samples, which for these systems provides minimized sample heating effects, an acceptable sample size and increased Overhauser DNP enhancements [21]. In comparison to standard, thermal-polarized FFC relaxometry, the reduced sample volume and polarization field strength for XBand DNP results in a reduced signal intensity when DNP signal enhancements are smaller than about 15. However, applications with limited sample amounts, measurements on insensitive heteronuclei and experiments that employ DNP to achieve selective detection may greatly benefit from X-Band DNP-enhanced FFC. With an outer diameter of only 19 mm the DNP probehead is compatible with a range of other FFC systems [11,68–71], enabling more widespread applications of DNP-enhanced FFC relaxometry. Furthermore, other X-Band DNP applications may employ such a compact resonator design to obtain increased MW conversion factors. Acknowledgments This research was funded by the Carl Zeiss Foundation. We thank Schlumberger Doll Research for providing the crude oil sample. References [1] A. Asano, NMR relaxation studies of elastomers, Annu. Rep. NMR Spectrosc. 86 (2015) 1–72. [2] H. Weingärtner, Understanding ionic liquids at the molecular level: facts, problems, and controversies, Angew. Chem. Int. Ed. 47 (2008) 654–670.

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