Friday, February 15, 2019

NMR study of optically hyperpolarized phosphorus donor nuclei in silicon #DNPNMR

Gumann, P., H. Haas, S. Sheldon, L. Zhu, R. Deshpande, T. Alexander, M. L. W. Thewalt, D. G. Cory, and C. Ramanathan. “NMR Study of Optically Hyperpolarized Phosphorus Donor Nuclei in Silicon.” Physical Review B 98, no. 18 (November 16, 2018). 


We use above-band-gap optical excitation, via a 1047-nm laser, to hyperpolarize the 31P spins in low-doped (ND = 6x10^15 cm−3) natural abundance silicon at 4.2 K and 6.7 T, and inductively detect the resulting NMR signal. The 30-kHz spectral linewidth observed is dramatically larger than the 600-Hz linewidth observed from a 28Si-enriched silicon crystal. We show that the broadening is consistent with previous electron-nuclear double-resonance results showing discrete isotope mass effect contributions to the donor hyperfine coupling. A secondary source of broadening is likely due to variations in the local strain, induced by the random distribution of different isotopes in natural silicon. The nuclear spin T1 and the buildup time for the optically induced 31P hyperpolarization in the natural abundance silicon sample were observed to be 178 +/- 47 and 69 +/- 6 s, respectively, significantly shorter than the values previously measured in 28Si-enriched samples under the same conditions. We measured the T1 and hyperpolarization buildup time for the 31P signal in natural abundance silicon at 9.4 T to be 54 +/- 31 and 13 +/- 2 s, respectively. The shorter buildup and nuclear spin T1 times at high field are likely due to the shorter electron spin T1, which drives nuclear spin relaxation via nonsecular hyperfine interactions. At 6.7 T, the phosphorus nuclear spin T2 was 16.7 +/- 1.6 ms at 4.2 K, a factor of 4 shorter than in 28Si-enriched crystals. This was observed to shorten to 1.9 +/- 0.4 ms in the presence of the infrared laser.

Wednesday, February 13, 2019

[NMR] Postdoc in biomolecular solid-state NMR in Strasbourg, France

Postdoctoral Position: Biomolecular Solid-state NMR 

The laboratory Membrane Biophysics and NMR at the University of Strasbourg has an opening for a postdoctoral position with experience in using solid-state NMR for the analysis of peptides and proteins. The aim of the project is to reveal the structural determinants that define the highly specific lipid recognition motif of a transmembrane protein and to characterize changes in structure, dynamics, oligomerization and topology of the protein as well as the lipids during recognition. Another ongoing project is the structural investigation of peptide fibers with strong nucleic acid and lentiviral transfection potential.

Candidates should have good experience in biomolecular solid-state NMR. Other techniques of the laboratory are solution NMR approaches, various types of biophysical methods, peptide synthesis and/or the biochemical production of proteins. Knowledge in some of these latter techniques are of advantage. S/he should have an interest in working in a highly interdisciplinary, international and collaborative environment. The project and position are funded by a three-year grant from the French National Agency for Research (ANR). The University of Strasbourg chemistry, life sciences and structural biology departments have excellent scientific records, with a multitude of collaborations world-wide.

Strasbourg is a very nice city on the French side of the Rhine river, at the border to Germany, with easy access to nearby mountains (Vosges, Black Forrest, Alps). Being in the heart of Europe it takes only short train rides to multiple destinations of scientific and/or touristic interest. 

Candidates should send their CV, publication list and contact info for three references to:

Prof. Burkhard Bechinger,


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[NMR] Post-doc position in dissolution DNP, Nantes, France


A post-doc position is available in the NMR group of the CEISAM laboratory, University of Nantes, France.

The postdoctoral researcher will join an ERC-funded project, led by Patrick Giraudeau, on the development of dissolution dynamic polarization for analytical chemistry. The project aims at bringing the reproducibility of dissolution DNP to the level that will unlock an array of applications in metabolomics and other “omics” sciences. This requires working at the interface between hardware development, NMR spectroscopy and analytical chemistry. 

The postdoctoral researcher will be in charge of harnessing -on a variety of complex biological samples (model mixtures, extracts, biofluids)- the potential of a new dissolution DNP system that will be installed in CEISAM during the summer 2019. In particular, the postdoctoral researcher will:

  • characterize the performance of the new d-DNP setting, and develop solutions to improve its reproducibility or to correct the effect of irreproducibility on the NMR signal;
  • evaluate the performance of the experimental setting on biological samples of increasing complexity;
  • apply the optimized experiments to a variety of “omics” research questions.

Research will involve close collaboration with the group of Prof. Sami Jannin (Université Claude Bernard Lyon 1, France) and with several French teams in metabolomics, as well as numerous interactions with Bruker Biospin. 

Applicants should hold a Ph.D. in chemistry or physics, and have a demonstrated track record in magnetic resonance instrumentation. Experience in DNP is desirable but not mandatory. Applicants should also show interest for applications to analytical chemistry. Good communication skills and a propensity for teamwork are also essential.

The NMR group of the CEISAM lab works on methods developments in solution-state NMR and their application to the analysis of mixtures. It is equipped with state-of-the-art NMR spectrometers, in the 400 to 700 MHz range. CEISAM is the molecular chemistry lab of the Université de Nantes and is a joint CNRS research unit, where research includes physical, theoretical and analytical chemistry, organic synthesis and catalysis, and chemical biology. The lab is located in the vibrant city of Nantes, close to the beautiful Atlantic coast of South Brittany.

The position is open from October 1st 2019. The net monthly salary will be between 2000 and 2300 €, depending on experience. The position is initially for 1 year but can be extended to 2 years.

Applications must be sent to patrick.giraudeau@univ-nantes.fr. Please include a cover letter, a CV, and 2 reference letters. Applications will be considered until the position is filled.

Recent publications:

J.-N. Dumez, J. Milani, B. Vuichoud, A. Bornet, J. Lalande-Martin, I. Tea, M. Yon, M. Maucourt, C. Deborde, A. Moing, L. Frydman, G. Bodenhausen, S. Jannin, P. Giraudeau, Hyperpolarized NMR of plant and cancer cell extracts at natural abundance, Analyst, 140, 5860-5863, (2015)

A. Bornet, M. Maucourt, C. Deborde, D. Jacob, J. Milani, B. Vuichoud, X. Ji, J.-N. Dumez, A. Moing, G. Bodenhausen, S. Jannin, P. Giraudeau, Highly Repeatable Dissolution Dynamic Nuclear Polarization for Heteronuclear NMR Metabolomics, Anal. Chem., 88, 6179–6183, (2016)

B. Plainchont, P. Berruyer, J.-N. Dumez, S. Jannin, P. Giraudeau, Dynamic Nuclear Polarization Opens New Perspectives for NMR Spectroscopy in Analytical Chemistry, Analytical Chemistry, 90, 3639-3650, (2018)


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Prof. Patrick GIRAUDEAU
CEISAM/Chemistry Department
Faculty of Science and Technology


Tel : (33)251125709

2 rue de la Houssinière BP 92208 
44322 Nantes Cedex 3 
FRANCE 



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Enhanced Dynamic Nuclear Polarization via Swept Microwave Frequency Combs #DNPNMR

Ajoy, A., R. Nazaryan, K. Liu, X. Lv, B. Safvati, G. Wang, E. Druga, et al. “Enhanced Dynamic Nuclear Polarization via Swept Microwave Frequency Combs.” Proceedings of the National Academy of Sciences 115, no. 42 (October 16, 2018): 10576–81. 


Dynamic nuclear polarization (DNP) has enabled enormous gains in magnetic resonance signals and led to vastly accelerated NMR/MRI imaging and spectroscopy. Unlike conventional cw-techniques, DNP methods that exploit the full electron spectrum are appealing since they allow direct participation of all electrons in the hyperpolarization process. Such methods typically entail sweeps of microwave radiation over the broad electron linewidth to excite DNP but are often inefficient because the sweeps, constrained by adiabaticity requirements, are slow. In this paper, we develop a technique to overcome the DNP bottlenecks set by the slow sweeps, using a swept microwave frequency comb that increases the effective number of polarization transfer events while respecting adiabaticity constraints. This allows a multiplicative gain in DNP enhancement, scaling with the number of comb frequencies and limited only by the hyperfine-mediated electron linewidth. We demonstrate the technique for the optical hyperpolarization of 13C nuclei in powdered microdiamonds at low fields, increasing the DNP enhancement from 30 to 100 measured with respect to the thermal signal at 7T. For low concentrations of broad linewidth electron radicals [e.g., TEMPO ((2,2,6,6- tetramethylpiperidin-1-yl)oxyl)], these multiplicative gains could exceed an order of magnitude.

Monday, February 11, 2019

Hyperpolarized 13C MR metabolic imaging can detect neuroinflammation in vivo in a multiple sclerosis murine model

Guglielmetti, Caroline, Chloé Najac, Alessandro Didonna, Annemie Van der Linden, Sabrina M. Ronen, and Myriam M. Chaumeil. “Hyperpolarized 13C MR Metabolic Imaging Can Detect Neuroinflammation in Vivo in a Multiple Sclerosis Murine Model.” Proceedings of the National Academy of Sciences 114, no. 33 (August 15, 2017): E6982–91. 


Proinflammatory mononuclear phagocytes (MPs) play a crucial role in the progression of multiple sclerosis (MS) and other neurodegenerative diseases. Despite advances in neuroimaging, there are currently limited available methods enabling noninvasive detection of MPs in vivo. Interestingly, upon activation and subsequent differentiation toward a proinflammatory phenotype MPs undergo metabolic reprogramming that results in increased glycolysis and production of lactate. Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) is a clinically translatable imaging method that allows noninvasive monitoring of metabolic pathways in real time. This method has proven highly useful to monitor the Warburg effect in cancer, through MR detection of increased HP [1-13C]pyruvate-tolactate conversion. However, to date, this method has never been applied to the study of neuroinflammation. Here, we questioned the potential of 13C MRSI of HP [1-13C]pyruvate to monitor the presence of neuroinflammatory lesions in vivo in the cuprizone mouse model of MS. First, we demonstrated that 13C MRSI could detect a significant increase in HP [1-13C]pyruvate-to-lactate conversion, which was associated with a high density of proinflammatory MPs. We further demonstrated that the increase in HP [1-13C]lactate was likely mediated by pyruvate dehydrogenase kinase 1 up-regulation in activated MPs, resulting in regional pyruvate dehydrogenase inhibition. Altogether, our results demonstrate a potential for 13C MRSI of HP [1-13C]pyruvate as a neuroimaging method for assessment of inflammatory lesions. This approach could prove useful not only in MS but also in other neurological diseases presenting inflammatory components.

Friday, February 8, 2019

A versatile custom cryostat for dynamic nuclear polarization supports multiple cryogenic magic angle spinning transmission line probes #DNPNMR

This article describes a heat exchanger used to generate cold gas for MAS-NMR experiments. Several different designs of this type of device have been described in the literature such as:


  1. The original design reported by Girffin et al.: https://doi.org/10.1016/0022-2364(91)90357-Y
  2. A counter flow heat exchanger reported by Zilm et al.: http://dx.doi.org/10.1016/j.jmr.2004.03.002


Scott, Faith J., Nicholas Alaniva, Natalie C. Golota, Erika L. Sesti, Edward P. Saliba, Lauren E. Price, Brice J. Albert, Pinhui Chen, Robert D. O’Connor, and Alexander B. Barnes. “A Versatile Custom Cryostat for Dynamic Nuclear Polarization Supports Multiple Cryogenic Magic Angle Spinning Transmission Line Probes.” Journal of Magnetic Resonance 297 (December 2018): 23–32.


Dynamic nuclear polarization (DNP) with cryogenic magic angle spinning (MAS) provides significant improvements in NMR sensitivity, yet presents unique technical challenges. Here we describe a custom cryostat and suite of NMR probes capable of manipulating nuclear spins with multi-resonant radiofrequency circuits, cryogenic spinning below 6 K, sample exchange, and microwave coupling for DNP. The corrugated waveguide and six transfer lines needed for DNP and cryogenic spinning functionality are coupled to the probe from the top of the magnet. Transfer lines are vacuum-jacketed and provide bearing and drive gas, variable temperature fluid, two exhaust pathways, and a sample ejection port. The cryostat thermally isolates the magnet bore, thereby protecting the magnet and increasing cryogen efficiency. This novel design supports cryogenic MAS-DNP performance over an array of probes without altering DNP functionality. We present three MAS probes (two supporting 3.2 mm rotors and one supporting 9.5 mm rotors) interfacing with the single cryostat. Mechanical details, transmission line radio frequency design, and performance of the cryostat and three probes are described.

Thursday, February 7, 2019

[NMR] Three PhD or Postdoc positions in NMR relaxation and DNP-NMR of polymers and complex fluids at TU Ilmenau, Germany

Employment opportunity

Within the group of Technical Physics II (Technische Physik II), the Technische Universität Ilmenau is offering up to

Three PhD student or postdoctoral positions
in 
Nuclear Magnetic Resonance of Polymers and Complex Fluids

Funded by the German Research Council DFG, we are continuing our research on polymer melts and solutions with an emphasis on new methods for polymer dynamics. Among other approaches, the project involves 1H and 2H relaxation dispersion investigations of isotopically diluted polymers with our two Stelar Fast Field Cycling (FFC) Relaxometers [Lozovoi et al., Macromolecules 51, 10055 (2018)]. Additional experiments will be carried out on a homebuilt Halbach magnet and commercial equipment (Bruker, Magritek). 

The second project involves application of the mentioned techniques to biomacromolecules, in particular to articular cartilage, with the aim of modelling molecular dynamics in biological tissue for which cartilage is a simple model system. Field-dependent relaxation times are well-known from medical MRI, but only empirically described in the literature; we want to establish a theoretical description of the frequency dependence as well as the width of relaxation times distributions in non-exponential signal decays [Petrov et al., Magn. Reson. Med., doi: 10.1002/mrm.27624 (2019)], and develop these findings into biomarkers for diseases such as osteoarthritis.

The third project focusses on the technical improvement or advanced application of DNP-FFC relaxometry studies. By combining DNP hardware with a FFC relaxometer, we have recently developed a novel platform to boost sensitivity and selectivity in complex fluids such as copolymers, porous media and multicomponent systems [Gizatullin et al., ChemPhysChem 18, 2347 (2017)], of which rocks and crude oil represent a naturally occurring example. Stable radicals are introduced and saturated by microwave irradiation, and subsequent magnetization transfer by either Overhauser or Solid Effect enhances the signal of nearby nuclei – including rare, insensitive and quadrupolar X nuclei – in the vicinity of the radical. Enhancement factors of several hundred have been achieved on our equipment. Depending on the skills and expertise of the candidate, the thesis can follow either a technical or an application focus.

We are seeking motivated individuals who are exploring applications of FFC and DNP-FFC within one of these projects. Requirements differ but typically involve sample preparation, modelling and potentially hardware or software development. Regular discussions and research stays with collaboration partners, mostly in Europe and USA, will be part of the project. This position requires skilled and enthusiastic persons, with an MSc degree in physics, chemistry or related disciplines, willing to work and actively participate in an international environment; a proven hands-on experience in ESR or NMR is a requirement, as are a strong background in NMR theory and programming skills.

The projects aim at obtaining a PhD level and are financed for an initial period of 3 years. The salary is according to the TV-L E13 scale of the German public sector (typically ¾ position depending on skills and experience). Under exceptional circumstances, a full salary postdoctoral position may be funded for a holder of a PhD title in one of these projects but with an initial contract period of 2 years. 

The Technische Universität Ilmenau aims to establish gender equality and strongly encourages applications by female candidates. Handicapped applicants with identical qualification will be considered with priority. Special services are available concerning all social matters. 

Please submit your application files (letter of application, complete CV, certificates, possibly references) preferably by February 28, 2019 to:

Prof. Siegfried Stapf, e-mail: siegfried.stapf@tu-ilmenau.de
_______________________________________________
Prof. Dr. Siegfried Stapf Technische Universität Ilmenau Fakultät für Mathematik und Naturwissenschaften FG Technische Physik II/Polymerphysik Postfach 100565 D-98684 Ilmenau Tel: +49 3677 69 3671 Fax: +49 3677 69 3770 

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Wednesday, February 6, 2019

Determination of binding affinities using hyperpolarized NMR with simultaneous 4-channel detection #DNPNMR

Kim, Yaewon, Mengxiao Liu, and Christian Hilty. “Determination of Binding Affinities Using Hyperpolarized NMR with Simultaneous 4-Channel Detection.” Journal of Magnetic Resonance 295 (October 2018): 80–86.


Dissolution dynamic nuclear polarization (D-DNP) is a powerful technique to improve NMR sensitivity by a factor of thousands. Combining D-DNP with NMR-based screening enables to mitigate solubility or availability problems of ligands and target proteins in drug discovery as it can lower the concentration requirements into the sub-micromolar range. One of the challenges that D-DNP assisted NMR screening methods face for broad application, however, is a reduced throughput due to additional procedures and time required to create hyperpolarization. These requirements result in a delay of several tens of minutes in-between each NMR measurement. To solve this problem, we have developed a simultaneous 4-channel detection method for hyperpolarized 19F NMR, which can increase throughput four-fold utilizing a purpose-built multiplexed NMR spectrometer and probe. With this system, the concentration-dependent binding interactions were observed for benzamidine and benzylamine with the serine protease trypsin. A T2 relaxation measurement of a hyperpolarized reporter ligand (TFBC; CF3C6H4CNHNH2), which competes for the same binding site on the trypsin with the other ligands, was used. The hyperpolarized TFBC was mixed with trypsin and the ligand of interest, and injected into four flow cells inside the NMR probe. Across the set of four channels, a concentration gradient was created. From the simultaneously acquired relaxation datasets, it was possible to determine the dissociation constant (KD) of benzamidine or benzylamine without the requirement for individually optimizing experimental conditions for different affinities. A simulation showed that this 4-channel detection method applied to D-DNP NMR extends the screenable KD range to up to three orders of magnitude in a single experiment.

Monday, February 4, 2019

Development of Millimeter Wave Fabry-Pérot Resonator for Simultaneous Electron-Spin and Nuclear Magnetic Resonance Measurement #DNPNMR

Ishikawa, Yuya, Kenta Ohya, Yutaka Fujii, Akira Fukuda, Shunsuke Miura, Seitaro Mitsudo, Hidetomo Yamamori, and Hikomitsu Kikuchi. “Development of Millimeter Wave Fabry-Pérot Resonator for Simultaneous Electron-Spin and Nuclear Magnetic Resonance Measurement.” Journal of Infrared, Millimeter, and Terahertz Waves 39, no. 4 (April 2018): 387–98.


We report a Fabry-Pérot resonator with spherical and flat mirrors to allow simultaneous electron-spin resonance (ESR) and nuclear magnetic resonance (NMR) measurements that could be used for double magnetic resonance (DoMR). In order to perform simultaneous ESR and NMR measurements, the flat mirror must reflect millimeter wavelength electromagnetic waves and the resonator must have a high Q value (Q > 3000) for ESR frequencies, while the mirror must simultaneously let NMR frequencies pass through. This requirement can be achieved by exploiting the difference of skin depth for the two frequencies, since skin depth is inversely proportional to the square root of the frequency. In consideration of the skin depth, the optimum conditions for conducting ESR and NMR using a gold thin film are explored by examining the relation between the Q value and the film thickness. A flat mirror with a gold thin film was fabricated by sputtering gold on an epoxy plate. We also installed a Helmholtz radio frequency coil for NMR and tested the system both at room and low temperatures with an optimally thick gold film. As a result, signals were obtained at 0.18 K for ESR and at 1.3 K for NMR. A flat-mirrored resonator with a thin gold film surface is an effective way to locate NMR coils closer to the sample being examined with DoMR.

[NMR] Solid-state NMR position @ University of Groningen (Netherlands) #ssNMR

Looking for: 

Solid-state NMR research technician (PhD/MSc)
University of Groningen, Zernike Institute for Advanced Materials
Van der Wel SSNMR group

— Deadline Feb. 14th — 

The Van der Wel solid-state NMR group at the University of Groningen (Netherlands) is looking for applicants with a background in NMR for a new research technician position in the lab. This position is funded by institutional support. The ideal candidate would have a MSc/PhD degree with a background in magic-angle-spinning solid-state NMR. However, we welcome applications by candidates with a strong background in NMR in general. Others with a potentially relevant expertise are encouraged to inquire (contact information below).

The group’s research focuses on the use of multidimensional magic-angle-spinning NMR in diverse contexts, with focal points being structural biology of protein misfolding diseases (including Huntington disease), membrane biophysics, and self-assembling bio-/nano-materials.

More background information about the lab and the research environment is on the group website: https://www.vanderwellab.org , and the institute/university website: https://www.rug.nl/research/zernike/

Potential applicants can find specific details about the position and application procedures (deadline Feb. 14th 2019) at the following URL:

Questions and inquiries should be sent to:
Patrick van der Wel – p.c.a.van.der.wel@rug.nl

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Patrick C.A. van der Wel, Ph.D.
Associate Professor
Solid-state NMR spectroscopy group
Zernike Institute for Advanced Materials
University of Groningen
Nijenborgh 4
9747 AG Groningen
The Netherlands

phone: +31(0)50-3632683

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Friday, February 1, 2019

A non-synthetic approach to extending the lifetime of hyperpolarized molecules using D2O solvation

Cho, Andrew, Roozbeh Eskandari, Vesselin Z. Miloushev, and Kayvan R. Keshari. “A Non-Synthetic Approach to Extending the Lifetime of Hyperpolarized Molecules Using D2O Solvation.” Journal of Magnetic Resonance 295 (October 2018): 57–62.


Although dissolution dynamic nuclear polarization is a robust technique to significantly increase magnetic resonance signal, the short T1 relaxation time of most 13C-nuclei limits the timescale of hyperpolarized experiments. To address this issue, we have characterized a non-synthetic approach to extend the hyperpolarized lifetime of 13C-nuclei in close proximity to solvent-exchangeable protons. Protons exhibit stronger dipolar relaxation than deuterium, so dissolving these compounds in D2O to exchange labile protons with solvating deuterons results in longer-lived hyperpolarization of the 13C-nucleus 2-bonds away. 13C T1 and T2 times were longer in D2O versus H2O for all molecules in this study. This phenomenon can be utilized to improve hyperpolarized signal-to-noise ratio as a function of longer T1, and enhanced spectral and imaging resolution via longer T2.