Richard J. Temkin

Dynamic nuclear polarization at high magnetic fields

Dynamic nuclear polarization (DNP) is a method that permits NMR signal intensities of solids and liquids to be enhanced significantly, and is therefore potentially an important tool in structural and mechanistic studies of biologically relevant molecules. During a DNP experiment, the large polarization of an exogeneous or endogeneous unpaired electron is transferred to the nuclei of interest (I) by microwave (microw) irradiation of the sample. The maximum theoretical enhancement achievable is given by the gyromagnetic ratios (gamma(e)gamma(l)), being approximately 660 for protons. In the early 1950s, the DNP phenomenon was demonstrated experimentally, and intensively investigated in the following four decades, primarily at low magnetic fields. This review focuses on recent developments in the field of DNP with a special emphasis on work done at high magnetic fields (> or =5 T), the regime where contemporary NMR experiments are performed. After a brief historical survey, we present a review of the classical continuous wave (cw) DNP mechanisms-the Overhauser effect, the solid effect, the cross effect, and thermal mixing. A special section is devoted to the theory of coherent polarization transfer mechanisms, since they are potentially more efficient at high fields than classical polarization schemes. The implementation of DNP at high magnetic fields has required the development and improvement of new and existing instrumentation. Therefore, we also review some recent developments in microw and probe technology, followed by an overview of DNP applications in biological solids and liquids. Finally, we outline some possible areas for future developments.

Vacuum Electronic High Power Terahertz Sources

Recent research and development has been incredibly successful at advancing the capabilities for vacuum electronic device (VED) sources of powerful terahertz (THz) and near-THz coherent radiation, both CW or average and pulsed. Currently, the VED source portfolio covers over 12 orders of magnitude in power (mW-to-GW) and two orders of magnitude in frequency (from <; 0.1 to >; 10 THz). Further advances are still possible and anticipated. They will be enabled by improved understanding of fundamental beam-wave interactions, electromagnetic mode competition and mode control, along with research and development of new materials, fabrication methods, cathodes, electron beam alignment and focusing, magnet technologies, THz metrology and advanced, broadband output radiation coupling techniques.

High Frequency Dynamic Nuclear Polarization

During the three decades 1980-2010, magic angle spinning (MAS) NMR developed into the method of choice to examine many chemical, physical, and biological problems. In particular, a variety of dipolar recoupling methods to measure distances and torsion angles can now constrain molecular structures to high resolution. However, applications are often limited by the low sensitivity of the experiments, due in large part to the necessity of observing spectra of low-γ nuclei such as the I = 1/2 species (13)C or (15)N. The difficulty is still greater when quadrupolar nuclei, such as (17)O or (27)Al, are involved. This problem has stimulated efforts to increase the sensitivity of MAS experiments. A particularly powerful approach is dynamic nuclear polarization (DNP) which takes advantage of the higher equilibrium polarization of electrons (which conventionally manifests in the great sensitivity advantage of EPR over NMR). In DNP, the sample is doped with a stable paramagnetic polarizing agent and irradiated with microwaves to transfer the high polarization in the electron spin reservoir to the nuclei of interest. The idea was first explored by Overhauser and Slichter in 1953. However, these experiments were carried out on static samples, at magnetic fields that are low by current standards. To be implemented in contemporary MAS NMR experiments, DNP requires microwave sources operating in the subterahertz regime, roughly 150-660 GHz, and cryogenic MAS probes. In addition, improvements were required in the polarizing agents, because the high concentrations of conventional radicals that are required to produce significant enhancements compromise spectral resolution. In the last two decades, scientific and technical advances have addressed these problems and brought DNP to the point where it is achieving wide applicability. These advances include the development of high frequency gyrotron microwave sources operating in the subterahertz frequency range. In addition, low temperature MAS probes were developed that permit in situ microwave irradiation of the samples. And, finally, biradical polarizing agents were developed that increased the efficiency of DNP experiments by factors of ∼4 at considerably lower paramagnet concentrations. Collectively, these developments have made it possible to apply DNP on a routine basis to a number of different scientific endeavors, most prominently in the biological and material sciences. This Account reviews these developments, including the primary mechanisms used to transfer polarization in high frequency DNP, and the current choice of microwave sources and biradical polarizing agents. In addition, we illustrate the utility of the technique with a description of applications to membrane and amyloid proteins that emphasizes the unique structural information that is available in these two cases.

Solid-state dynamic nuclear polarization at 263 GHz: spectrometer design and experimental results

Dynamic Nuclear Polarization (DNP) experiments transfer polarization from electron spins to nuclear spins with microwave irradiation of the electron spins for enhanced sensitivity in nuclear magnetic resonance (NMR) spectroscopy. Design and testing of a spectrometer for magic angle spinning (MAS) DNP experiments at 263 GHz microwave frequency, 400 MHz (1)H frequency is described. Microwaves are generated by a novel continuous-wave gyrotron, transmitted to the NMR probe via a transmission line, and irradiated on a 3.2 mm rotor for MAS DNP experiments. DNP signal enhancements of up to 80 have been measured at 95 K on urea and proline in water-glycerol with the biradical polarizing agent TOTAPOL. We characterize the experimental parameters affecting the DNP efficiency: the magnetic field dependence, temperature dependence and polarization build-up times, microwave power dependence, sample heating effects, and spinning frequency dependence of the DNP signal enhancement. Stable system operation, including DNP performance, is also demonstrated over a 36 h period.

Characteristics and applications of fast-wave gyrodevices

Gyrodevice oscillators and amplifiers (or gyro-oscillators and gyro-amplifiers) are being utilized in a variety of applications where high power levels are required at millimeter-wave frequencies. Gyro-oscillators, developed primarily for magnetic fusion research applications, have achieved power levels near 1 MW for pulse durations in excess of 1 s at frequencies above 100 GHz. Continued work on these devices should enable them to achieve continuous-wave operation at multimegawatt power levels at frequencies in the 100-GHz to 200-GHz range, thereby meeting the requirements of planned magnetic fusion experiments. The development of gyro-oscillators for fusion experiments has led to the utilization of the devices in several industrial applications, such as ceramic sintering and metal joining. Activities in this area involve adapting the oscillators to the industrial environment where reliability, efficiency, and ease of operation are paramount. Gyro-amplifiers are being developed for applications requiring phase coherence and instantaneous bandwidth, such as in linear accelerators and millimeter-wave radar. Impressive results from X-band to W-band already suggest the promise of these devices. Potential new applications and novel gyrodevice design approaches continue to attract the attention of researchers around the world.

Second harmonic operation at 460 GHz and broadband continuous frequency tuning of a gyrotron oscillator

We report the short-pulse operation of a 460 GHz gyrotron oscillator both at the fundamental (near 230 GHz) and second harmonic (near 460 GHz) of electron cyclotron resonance. During operation in a microsecond pulse length regime with 13-kV beam voltage and 110-mA beam current, the instrument generates several watts of power in two second harmonic modes, the TE/sub 2,6,1/ at 456.15 GHz and the TE/sub 0,6,1/ at 458.56 GHz. Operation in the fundamental modes, including the TE/sub 0,3,1/ mode at 237.91 GHz and the TE/sub 2,3,1/ at 233.15 GHz, is observed at output powers up to 70 W. Further, we demonstrate broadband continuous frequency tuning of the fundamental modes of the oscillator over a range of more than 2 GHz through variation of the magnetic field alone. We interpret these results in terms of smooth transitions between higher order axial modes of the resonator. The 460 GHz gyrotron is currently being processed for continuous duty operation, where it will serve as a microwave source for sensitivity-enhanced nuclear magnetic resonance (dynamic nuclear polarization) studies at 16 T (700 MHz /sup 1/H), a field strength which is two-fold higher than has been accessible with previous technology.

High frequency (140 GHz) dynamic nuclear polarization: Polarization transfer to a solute in frozen aqueous solution

Dynamic nuclear polarization (DNP) transfers the large polarization of unpaired electrons to nuclei and thus significantly enhances the signal strength in nuclear magnetic resonance (NMR) spectroscopy. High frequency/field (140 GHz/5 T) DNP has been implemented in solid state NMR experiments using a nitroxide radical as the paramagnetic polarizing agent in a water:glycerol frozen solution. The 1H and 13C NMR signal strengths of both the solvent and an amino acid solute have been enhanced by a factor of 185, which represents a reduction of ≳102 in sample size requirements or ≳104 in signal acquisition time.

Continuous-Wave Operation of a Frequency-Tunable 460-GHz Second-Harmonic Gyrotron for Enhanced Nuclear Magnetic Resonance

The design, operation, and characterization of a continuous-wave (CW) tunable second-harmonic 460-GHz gyrotron are reported. The gyrotron is intended to be used as a submillimeter-wave source for 700-MHz nuclear magnetic resonance experiments with sensitivity enhanced by dynamic nuclear polarization. The gyrotron operates in the whispering-gallery mode TE11,2 and has generated 16 W of output power with a 13-kV 100-mA electron beam. The start oscillation current measured over a range of magnetic field values is in good agreement with theoretical start currents obtained from linear theory for successive high-order axial modes TE11,2,q. The minimum start current is 27 mA. Power and frequency tuning measurements as a function of the electron cyclotron frequency have also been carried out. A smooth frequency tuning range of 1 GHz was obtained for the operating second-harmonic mode either by magnetic field tuning or beam voltage tuning. Long-term CW operation was evaluated during an uninterrupted period of 48 h, where the gyrotron output power and frequency were kept stable to within ±0.7% and ±6 ppm, respectively, by a computerized control system. Proper operation of an internal quasi-optical mode converter implemented to transform the operating whispering-gallery mode to a Gaussian-like beam was also verified. Based on the images of the gyrotron output beam taken with a pyroelectric camera, the Gaussian-like mode content of the output beam was computed to be 92% with an ellipticity of 12%.

Simulation of Photonic Band Gaps in Metal Rod Lattices for Microwave Applications

We have derived the global band gaps for general two-dimensional (2D) photonic band gap (PBG) structures formed by square or triangular arrays of metal posts. Such PBG structures have many promising applications in active and passive devices at microwave, millimeter wave, and higher frequencies. A coordinate-space, finite-difference code, called the photonic band gap structure simulator (PBGSS), was developed to calculate complete dispersion curves for lattices for a series of values of the ratio of the post radius (r) to the post spacing (a). The fundamental and higher frequency global photonic band gaps were determined numerically. These universal curves should prove useful in PBG cavity design. In addition, for very long wavelengths, where the numerical methods of the PBGSS code are difficult, dispersion curves were derived for the transverse-magnetic (TM) mode by an approximate, quasi-static approach. Results of this approach agree well with the PBGSS code for r/a<0.1. The present results are compared...

Continuous-wave operation of a 460-GHz second harmonic gyrotron oscillator

We report the regulated continuous-wave (CW) operation of a second harmonic gyrotron oscillator at output power levels of over 8 W (12.4 kV and 135 mA beam voltage and current) in the TE0,6,1 mode near 460 GHz. The gyrotron also operates in the second harmonic TE2,6,1 mode at 456 GHz and in the TE2,3,1 fundamental mode at 233 GHz. CW operation was demonstrated for a one-hour period in the TE 0,6,1 mode with better than 1% power stability, where the power was regulated using feedback control. Nonlinear simulations of the gyrotron operation agree with the experimentally measured output power and radio-frequency (RF) efficiency when cavity ohmic losses are included in the analysis. The output radiation pattern was measured using a pyroelectric camera and is highly Gaussian, with an ellipticity of 4%. The 460-GHz gyrotron will serve as a millimeter-wave source for sensitivity-enhanced nuclear magnetic resonance (dynamic nuclear polarization) experiments at a magnetic field of 16.4 T