Feb 18, 2019

Hyperpolarized NMR Spectroscopy: d-DNP, PHIP, and SABRE Techniques #DNPNMR

Kovtunov, Kirill V., Ekaterina V. Pokochueva, Oleg G. Salnikov, Samuel F. Cousin, Dennis Kurzbach, Basile Vuichoud, Sami Jannin, et al. “Hyperpolarized NMR Spectroscopy: D-DNP, PHIP, and SABRE Techniques.” Chemistry - An Asian Journal 13, no. 15 (August 6, 2018): 1857–71.

The intensity of NMR signals can be enhanced by several orders of magnitude by using various techniques for the hyperpolarization of different molecules. Such approaches can overcome the main sensitivity challenges facing modern NMR/magnetic resonance imaging (MRI) techniques, whilst hyperpolarized fluids can also be used in a variety of applications in material science and biomedicine. This Focus Review considers the fundamentals of the preparation of hyperpolarized liquids and gases by using dissolution dynamic nuclear polarization (d-DNP) and parahydrogen- based techniques, such as signal amplification by reversible exchange (SABRE) and parahydrogen-induced polarization (PHIP), in both heterogeneous and homogeneous processes. The various new aspects in the formation and utilization of hyperpolarized fluids, along with the possibility of observing NMR signal enhancement, are described.

Feb 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.

Feb 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)


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 

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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.

Feb 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.

Feb 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.