Monday, June 30, 2014

High DNP efficiency of TEMPONE radicals in liquid toluene at low concentrations

Enkin, N., et al., High DNP efficiency of TEMPONE radicals in liquid toluene at low concentrations. Phys Chem Chem Phys, 2014. 16(19): p. 8795-800.

We show that at low concentrations (</=5 mM) TEMPONE radicals in liquid toluene exhibit higher DNP efficiency than in water. In spite of reduced coupling factors, the improved DNP performance in toluene results from favourable saturation and leakage factors, as determined by pulse electron-electron double resonance (ELDOR) and NMR relaxation, respectively. The extracted coupling factors at 0.35 Tesla support theoretical predictions of the Overhauser mechanism.

Friday, June 27, 2014

Liquid state dynamic nuclear polarization of ethanol at 3.4 T (95 GHz)

van der Heijden, G.H., A.P. Kentgens, and P.J. van Bentum, Liquid state dynamic nuclear polarization of ethanol at 3.4 T (95 GHz). Phys Chem Chem Phys, 2014. 16(18): p. 8493-502.

Dynamic Nuclear Polarization (DNP) in the liquid state has become the focus of attention to improve the NMR sensitivity of mass limited samples. The Overhauser model predicts a fast reduction in DNP enhancement at high magnetic fields where the electron Larmor frequency exceeds the typical inverse correlation time of the magnetic interaction between an unpaired electron spin of a radical and proton spins of the solvent molecules. The Overhauser hard sphere model is able to predict quantitatively the DNP enhancement for water TEMPOL solutions. The increase in temperature due to dielectric heating of the sample acts to reduce the correlation times and allows a substantial Overhauser DNP. In this paper we extend the work done on water towards other small molecules, such as ethanol. Experimentally we observe a similar enhancement for all three proton groups in the ethanol molecule. The classical interpretation of the low field Overhauser experiments on ethanol invokes a very fast anisotropic rotation of the hydrogen bonded TEMPOL-ethanol complex to explain the fast relaxation of the OH proton. Here we will discuss W-band relaxation and DNP enhancement within this classical model. Although the description can be made quantitative, the invoked parameters do not seem to be realistic. We will propose an alternative model based on the dynamic interaction both in free collision and due to modulation of the hydrogen bond length of the complex.

Monday, June 23, 2014

Open Position at Bridge12 Technologies

Bridge12 is a high-growth startup focusing on the development of cutting-edge microwave and terahertz (THz) instrumentation for use in scientific research such as magnetic resonance spectroscopy (DNP, NMR, EPR), communication systems and industrial applications. The company has a worldwide customer base and conducts groundbreaking research on applications of microwave/THz radiation in novel fields, often in collaboration with leading academic institutes. The company has a proven track record of securing Small Business Innovation Research (SBIR) grants from agencies across all fields.

As a scientist at Bridge12, you will work on multidisciplinary projects that involve all aspects of microwave/THz instrumentation design, development of prototypes and conduct research. The position requires creativity in a wide range of areas in the life science area and project management skills. We are looking for a self-starter who enjoys an innovative, interdisciplinary environment and the challenges that come with the manufacturing of high-tech, scientific instrumentation. You will also have the opportunity to write research grant proposals to federal research agencies and define your own research scope within the scientific areas of interest of Bridge12. This will involve developing the project plan and setting milestones and budget for you projects. You will work out of the Bridge12 facilities in Framingham, MA and only occasional travel is associated with this position (conferences, tradeshows or meetings with collaborators).

  • Development of microwave/THz instrumentation for application in DNP-enhanced NMR spectroscopy. This includes the electrical and mechanical design and fabrication of NMR probes, active and passive microwave/THz components (e.g. transmission lines, mirrors, bends, quasi-optical components), RF circuits and cryogenics
  • Plan and conduct research experiments sometimes in collaboration with Bridge12 research partners (e.g. Harvard Medical School at the Massachusetts General Hospital)
Required Skills & Experience
  • Good understanding of the principles of magnetic resonance spectroscopy (NMR, EPR, MRI), NMR instrumentation and software and knowledge of modern NMR techniques and applications in the material science and life science area
  • Experience in performing electromagnetic simulations for RF and microwave/THz circuits using finite element analysis (e.g. Ansys HFSS)
  • Experience with 3D CAD tools for mechanical design such as Autodesk Inventor
  • Operating test equipment such as Vector Network Analyzers (RF to THz frequencies), oscilloscopes
  • Excellent verbal and written communication skills and good team work ethics
  • Experience in grant proposal writing (advantage)
  • Printed Circuit Board design and prototyping (advantage)
  • Experience in designing cyrogenic instrumentation (advantage)
  • Experience in using Python, Matlab, LabVIEW (advantage)
Qualification: MS (or BS) degree in science, preferable in chemical engineering, physical chemistry or equivalent areas.

This is a full-time position. Bridge12 is an equal opportunity employer, and offers a competitive compensation package with excellent benefits. In compliance with federal law, all persons hired will be required to verify identity and eligibility to work in the United States and to complete the required employment eligibility verification document form upon hire.

Please email your Resume or CV together with a cover letter to: (reference number S031406)

Kokorin, A.I., V.N. Khrustalev, and E.N. Golubeva, The Structure and EPR Behavior of Short Nitroxide Biradicals Containing Sulfur Atom in the Bridge. Appl. Magn. Reson., 2014. 45(4): p. 397-409.

Two short nitroxide biradicals of similar composition: S(OR6)2 (1) and O=S(OR6)2 (2), where OR6 is 1-oxyl-2,2,6,6-tetramethyl-4-oxypiperidine, have been studied by electron paramagnetic resonance spectroscopy, and X-ray structural analysis. Variations of the intramolecular electron spin exchange in the biradicals, dissolved in toluene and ethanol, as a function of temperature were characterized by changes in the isotropic 14N hyperfine splitting constant a, values of the exchange integral J and compared with the X-ray structural data. Thermodynamic parameters of the conformational rearrangements were calculated. Geometry optimization and spin density distribution calculations of biradicals 1 and 2 were carried out on the DFT/UB3LYP/cc-pVdz and DFT/ROPBE/N07D levels of theory. Structural rigidity and probable differences in biradicals behavior are discussed.

Friday, June 20, 2014

Role of Electron Spin Dynamics on Solid-State Dynamic Nuclear Polarization Performance

Siaw, T.A., et al., Role of Electron Spin Dynamics on Solid-State Dynamic Nuclear Polarization Performance. Phys. Chem. Chem. Phys., 2014.

For the broadest dissemination of solid-state dynamic nuclear polarization (ssDNP) enhanced NMR as a materials characterization tool, the ability to employ generic mono-nitroxide radicals as spin probes is critical. A better understanding of the factors contributing to ssDNP efficiency is needed to rationally optimize the experimental condition for the practically accessible spin probes at hand. This study seeks to advance the mechanistic understanding of ssDNP by examining the effect of electron spin dynamics on the ssDNP performance at liquid helium temperatures (4-40 K). The key observation is that bi-radicals and mono-radicals can generate comparable nuclear spin polarization at 4 K and 7 T, which is in contrast to ssDNP at liquid nitrogen temperatures (80-150 K) that find bi-radicals to clearly outperform mono-radicals. To rationalize this observation, we analyze the change in the DNP-induced nuclear spin polarization (Pn) and the characteristic ssDNP signal buildup time as a function of electron spin relaxation rates that are modulated by the mono- and bi-radical spin concentration. Changes in Pn are consistent with a systematic variation in the product of the electron spin-lattice relaxation time and the electron spin flip-flop rate that constitutes an integral saturation factor of an inhomogeneously broadened EPR spectrum. We show that the comparable Pn achieved with both radical species can be reconciled with a comparable integral EPR saturation factor. Surprisingly, the largest Pn is observed at an intermediate spin concentration for both the mono- and bi-radicals. At the highest radical concentration, the stronger inter-electron spin dipolar coupling favors ssDNP, while oversaturation diminishes Pn, as experimentally verified with the observation of a maximum Pn at an intermediate, not the maximum, microwave ([small mu ]w) power. At the maximum [small mu ]w power, oversaturation reduces the electron spin population differential that must be upheld between electron spins that span a frequency difference matching the 1H NMR frequency-characteristic of the cross effect DNP. This new mechanistic insight allows us to rationalize experimental conditions where generic mono-nitroxide probes can offer competitive ssDNP performance to that of custom designer bi-radicals, and thus helps vastly expand the application scope of ssDNP for the study of functional materials and solids.

Wednesday, June 18, 2014

Optimizing sample preparation methods for dynamic nuclear polarization solid-state NMR of synthetic polymers

Le, D., et al., Optimizing sample preparation methods for dynamic nuclear polarization solid-state NMR of synthetic polymers. Macromolecules, 2014: p. 140613123939001.

This work compares the overall sensitivity enhancements provided by dynamic nuclear polarization (DNP) for the solid-state NMR characterization of polymer samples doped with biradicals and prepared either by film casting (FC), or by glass forming (GF) using 1,1,2,2-tetrachloroethane as the solvent. Analysis of amorphous and semicrystalline polymers (polystyrene, poly(ethylene oxide), polylactide, poly(methyl methacrylate)) of varying molecular weights showed that GF provided larger sensitivity enhancements than FC but yielded DNP-enhanced 13C CPMAS spectra of lower resolution for semicrystalline polymers, owing to line-broadening due to conformational distribution of the polymer chains in frozen solution. Moreover, use of deuterated solvents significantly reduced the intensity of the solvent signals in the DNP-enhanced 13C CPMAS spectra of polymers prepared by GF, while preserving the sensitivity enhancement observed for the polymer signals. For the polymers investigated here, both FC and GF performed better than incipient wetness impregnation, yielding overall sensitivity enhancements between 5 and 40.

Monday, June 16, 2014

High-resolution NMR spectroscopy of encapsulated proteins dissolved in low-viscosity fluids

Some more information on encapsulated proteins, an approach that was shown recently to be a very interesting path for solution-state DNP by the same group.

Nucci, N.V., K.G. Valentine, and A.J. Wand, High-resolution NMR spectroscopy of encapsulated proteins dissolved in low-viscosity fluids. J Magn Reson, 2014. 241(0): p. 137-47.

High-resolution multi-dimensional solution NMR is unique as a biophysical and biochemical tool in its ability to examine both the structure and dynamics of macromolecules at atomic resolution. Conventional solution NMR approaches, however, are largely limited to examinations of relatively small (<25kDa) molecules, mostly due to the spectroscopic consequences of slow rotational diffusion. Encapsulation of macromolecules within the protective nanoscale aqueous interior of reverse micelles dissolved in low viscosity fluids has been developed as a means through which the 'slow tumbling problem' can be overcome. This approach has been successfully applied to diverse proteins and nucleic acids ranging up to 100kDa, considerably widening the range of biological macromolecules to which conventional solution NMR methodologies may be applied. Recent advances in methodology have significantly broadened the utility of this approach in structural biology and molecular biophysics.

Friday, June 13, 2014

Bolus tracking for improved metabolic imaging of hyperpolarised compounds

Durst, M., et al., Bolus tracking for improved metabolic imaging of hyperpolarised compounds. J. Magn. Reson., 2014. 243(0): p. 40-46.

Dynamic nuclear polarisation has enabled real-time metabolic imaging of pyruvate and its metabolites. Conventional imaging sequences rely on predefined settings and do not account for intersubject variations in biological parameters such as perfusion. We present a fully automatic real-time bolus tracking sequence for hyperpolarised substrates which starts the imaging acquisition at a defined point on the bolus curve. This reduces artefacts due to signal change and allows for a more efficient use of hyperpolarised magnetisation. For single time point imaging methods, bolus tracking enables a more reliable and consistent quantification of metabolic activity. An RF excitation with a small flip angle is used to obtain slice-selective pyruvate tracking information in rats. Moreover, in combination with a copolarised urea and pyruvate injection, spectrally selective tracking on urea allows obtaining localised bolus tracking information without depleting the pyruvate signal. Particularly with regard to clinical application, the bolus tracking technique could provide an important step towards a routine assessment protocol which removes operator dependencies and ensures comparable results.

Wednesday, June 11, 2014

Sensitivity enhancement in solution NMR: emerging ideas and new frontiers

Lee, J.H., Y. Okuno, and S. Cavagnero, Sensitivity enhancement in solution NMR: emerging ideas and new frontiers. J Magn Reson, 2014. 241(0): p. 18-31.

Modern NMR spectroscopy has reached an unprecedented level of sophistication in the determination of biomolecular structure and dynamics at atomic resolution in liquids. However, the sensitivity of this technique is still too low to solve a variety of cutting-edge biological problems in solution, especially those that involve viscous samples, very large biomolecules or aggregation-prone systems that need to be kept at low concentration. Despite the challenges, a variety of efforts have been carried out over the years to increase sensitivity of NMR spectroscopy in liquids. This review discusses basic concepts, recent developments and future opportunities in this exciting area of research.

Monday, June 9, 2014

DNP-enhanced MAS NMR of bovine serum albumin sediments and solutions

Ravera, E., et al., DNP-enhanced MAS NMR of bovine serum albumin sediments and solutions. J Phys Chem B, 2014. 118(11): p. 2957-65.

Protein sedimentation sans cryoprotection is a new approach to magic angle spinning (MAS) and dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) spectroscopy of proteins. It increases the sensitivity of the experiments by a factor of approximately 4.5 in comparison to the conventional DNP sample preparation and circumvents intense background signals from the cryoprotectant. In this paper, we investigate sedimented samples and concentrated frozen solutions of natural abundance bovine serum albumin (BSA) in the absence of a glycerol-based cryoprotectant. We observe DNP signal enhancements of epsilon approximately 66 at 140 GHz in a BSA pellet sedimented from an aqueous solution containing the biradical polarizing agent TOTAPOL and compare this with samples prepared using the conventional protocol (i.e., dissolution of BSA in a glycerol/water cryoprotecting mixture). The dependence of DNP parameters on the radical concentration points to the presence of an interaction between TOTAPOL and BSA, so much so that a frozen solution sans cryoprotectant still gives epsilon approximately 50. We have studied the interaction of BSA with another biradical, SPIROPOL, that is more rigid than TOTAPOL and has been reported to give higher enhancements. SPIROPOL was also found to interact with BSA, and to give epsilon approximately 26 close to its maximum achievable concentration. Under the same conditions, TOTAPOL gives epsilon approximately 31, suggesting a lesser affinity of BSA for SPIROPOL with respect to TOTAPOL. Altogether, these results demonstrate that DNP is feasible in self-cryoprotecting samples.

Friday, June 6, 2014

Remote sensing of sample temperatures in nuclear magnetic resonance using photoluminescence of semiconductor quantum dots

This article is not exclusively about DNP-NMR spectroscopy, but describes an interesting approach of measuring cryogenic temperatures using a simple fiber optic-based setup. It is particularly useful for low-temperature MAS NMR experiments, including DNP-NMR spectroscopy.

Tycko, R., Remote sensing of sample temperatures in nuclear magnetic resonance using photoluminescence of semiconductor quantum dots. J Magn Reson, 2014. 244C(0): p. 64-67.

Knowledge of sample temperatures during nuclear magnetic resonance (NMR) measurements is important for acquisition of optimal NMR data and proper interpretation of the data. Sample temperatures can be difficult to measure accurately for a variety of reasons, especially because it is generally not possible to make direct contact to the NMR sample during the measurements. Here I show that sample temperatures during magic-angle spinning (MAS) NMR measurements can be determined from temperature-dependent photoluminescence signals of semiconductor quantum dots that are deposited in a thin film on the outer surface of the MAS rotor, using a simple optical fiber-based setup to excite and collect photoluminescence. The accuracy and precision of such temperature measurements can be better than +/-5K over a temperature range that extends from approximately 50K (-223 degrees C) to well above 310K (37 degrees C). Importantly, quantum dot photoluminescence can be monitored continuously while NMR measurements are in progress. While this technique is likely to be particularly valuable in low-temperature MAS NMR experiments, including experiments involving dynamic nuclear polarization, it may also be useful in high-temperature MAS NMR and other forms of magnetic resonance.

Wednesday, June 4, 2014

Static (1)H dynamic nuclear polarization with the biradical TOTAPOL: a transition between the solid effect and the cross effect

Shimon, D., et al., Static (1)H dynamic nuclear polarization with the biradical TOTAPOL: a transition between the solid effect and the cross effect. Phys Chem Chem Phys, 2014. 16(14): p. 6687-99.

To study the solid state (1)H-DNP mechanism of the biradical TOTAPOL under static conditions the frequency swept DNP enhancement spectra of samples containing 20 mM and 5 mM TOTAPOL were measured as a function of MW irradiation time and temperature. We observed that under static DNP conditions the biradical TOTAPOL behaves similar to the monoradical TEMPOL, in contrast to MAS DNP where TOTAPOL is considerably more effective. As previously done for TEMPOL, the TOTAPOL DNP spectra were analyzed taking a superposition of a basic SE-DNP lineshape and a basic CE-DNP lineshape with different amplitudes. The analysis of the steady state DNP spectra showed that the SE was dominant in the 6-10 K range and the CE was dominant above 10 K. DNP spectra obtained as a function of MW irradiation time allowed resolving the individual SE and CE buildup times. At low temperatures the SE buildup time was faster than the CE buildup time and at all temperatures the CE buildup time was close to the nuclear spin-lattice relaxation time, T1n. Polarization calculations involving nuclear spin-diffusion for a model system of one electron and many nuclei suggested that the shortening of the T1n for increasing temperatures is the reason why the SE contribution to the overall enhancement was reduced.

Monday, June 2, 2014

In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

Schmidt, R., et al., In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding. J Magn Reson, 2014. 240(0): p. 8-15.

Hyperpolarized metabolic imaging is a growing field that has provided a new tool for analyzing metabolism, particularly in cancer. Given the short life times of the hyperpolarized signal, fast and effective spectroscopic imaging methods compatible with dynamic metabolic characterizations are necessary. Several approaches have been customized for hyperpolarized (13)C MRI, including CSI with a center-out k-space encoding, EPSI, and spectrally selective pulses in combination with spiral EPI acquisitions. Recent studies have described the potential of single-shot alternatives based on spatiotemporal encoding (SPEN) principles, to derive chemical-shift images within a sub-second period. By contrast to EPSI, SPEN does not require oscillating acquisition gradients to deliver chemical-shift information: its signal encodes both spatial as well as chemical shift information, at no extra cost in experimental complexity. SPEN MRI sequences with slice-selection and arbitrary excitation pulses can also be devised, endowing SPEN with the potential to deliver single-shot multi-slice chemical shift images, with a temporal resolution required for hyperpolarized dynamic metabolic imaging. The present work demonstrates this with initial in vivo results obtained from SPEN-based imaging of pyruvate and its metabolic products, after injection of hyperpolarized [1-(13)C]pyruvate. Multi-slice chemical-shift images of healthy rats were obtained at 4.7T in the region of the kidney, and 4D (2D spatial, 1D spectral, 1D temporal) data sets were obtained at 7T from a murine lymphoma tumor model.