Category Archives: dDNP

Design of a local quasi-distributed tuning and matching circuit for dissolution DNP cross polarization #DNPNMR

Vinther, Joachim M.O., Vitaliy Zhurbenko, Mohammed M. Albannay, and Jan Henrik Ardenkjær-Larsen. “Design of a Local Quasi-Distributed Tuning and Matching Circuit for Dissolution DNP Cross Polarization.” Solid State Nuclear Magnetic Resonance 102 (October 2019): 12–20.

https://doi.org/10.1016/j.ssnmr.2019.04.006

Dynamic nuclear polarization (DNP) build-up times at low temperature for low-gamma nuclei can be unfavorably long and can be accelerated by transfer of polarization from protons. The efficiency of the cross polarization (CP) depends on the B1-field strengths, the pulse sequence chosen for cross polarization and the sample composition. CP experiments rely on high B1-fields, which typically lead to electrical discharge and breakdown in the circuit. This problem is particularly severe in the low pressure helium atmosphere due to easily ionized helium atoms. The purpose of this study is to identify strategies to minimize voltages across components in a tuning and matching circuit of the coil to avoid electrical discharge during CP experiments. Design equations for three tuning and matching network configurations are derived. The results of the study are then used in the design of a single coil double resonance DNP probe operating at 71.8 MHz (13C frequency) and 285.5 MHz (1H frequency). In the current setup we achieve 28% polarization on 13C in urea with a build-up time of 11.6 min with CP compared to 14% and 53 min by direct polarization using TEMPOL as the radical. Different cross polarization sequences are compared.

Hyperpolarized Water Enhances Two-Dimensional Proton NMR Correlations: A New Approach for Molecular Interactions #DNPNMR

Sadet, Aude, Cristina Stavarache, Mihaela Bacalum, Mihai Radu, Geoffrey Bodenhausen, Dennis Kurzbach, and Paul R. Vasos. “Hyperpolarized Water Enhances Two-Dimensional Proton NMR Correlations: A New Approach for Molecular Interactions.” Journal of the American Chemical Society 141, no. 32 (August 14, 2019): 12448–52.

https://doi.org/10.1021/jacs.9b03651.

Proteins and peptides interactions are characterized in the liquid state by multidimensional NMR spectroscopy experiments, which can take hours to record. We show that, starting from hyperpolarized HDO, two-dimensional (2D) proton correlation maps of a peptide, either free in solution or interacting with liposomes, can be acquired in less than 60 s. In standard 2D NMR spectroscopy without hyperpolarization, the acquisition time required for similar spectral correlations is of the order of hours. This hyperpolarized experiment allows to identify amino-acids featuring solvent-interacting hydrogens and provides fast spectroscopic analysis of peptide conformers. These experiments are a useful and straightforward tool for biochemistry and structural biology, as they do not recur to nitrogen-15 or carbon-13 isotope enrichment.

Hyperpolarized MR – What’s up Doc? #DNPNMR

Ardenkjaer-Larsen, Jan H. “Hyperpolarized MR – What’s up Doc?” Journal of Magnetic Resonance 306 (September 2019): 124–27.

https://doi.org/10.1016/j.jmr.2019.07.017

Hyperpolarized MR by dissolution Dynamic Nuclear Polarization (dDNP) appeared on the scene in 2003. Since then, it has been translated to the clinic and several sites are now conducting human studies. This has happened at record pace despite all its complexities. The method has reached a pivotal point, and the coming years will be critical in realizing its full potential. Though the field has been characterized by strong collaboration between academia, government and industry, the key message of this perspective paper is that accelerated consensus building is of the essence in fulfilling the original vision for the method and ensuring widespread adoption. The challenge is to gain acceptance among clinicians based on strong indications and clear evidence. The future appears bright; initial clinical data looks promising and the scope for improvement is significant.

[NMR] Postdoctoral position in DNP-enhanced Magnetic Resonance #DNPNMR

Postdoctoral Researcher in DNP-enhanced Magnetic Resonance 

Barcelona, Spain

A postdoctoral research position is available starting from January 1st 2020 at the Institute for Bioengineering of Catalonia (IBEC), funded by an EU Horizon 2020 Future Emerging Technologies (H2020 FET-OPEN) grant. 

The position is fully funded for a period of up to 36 months.

The project we offer concerns real-time study of metabolism in engineered “organ-on-a-chip” tissue systems via hyperpolarized magnetic resonance. As part of our efforts to create non-invasive platforms for tailored drug testing, the successful candidate will be involved in the development of Carbon-13 hyperpolarization methods, as well as carrying out innovative work on the tissue engineering side of the project. 

Applicants should have a Ph.D. in engineering, physics, or chemistry. Previous experience in nuclear magnetic resonance or magnetic resonance imaging is necessary. Experience with 13C hyperpolarization, magnetic resonance hardware, data acquisition and signal/image processing is strongly favored. Knowledge of C++, Matlab, Python, and magnetic resonance spectrometer programming languages, will also be evaluated. Applicants should also have a strong track record of publications in peer-reviewed scientific journals and excellent communication skills.

Environment:

The Institute for Bioengineering of Catalonia (IBEC) is a research institute covering most bioengineering fields, from basic research to medical applications. IBEC is located at the Barcelona Science Park (PCB, www.pcb.ub.edu) in central Barcelona, and has strong connections with the nearby Bellvitge University Hospital (BUH). The researcher will have access to a commercial DNP instrument (3.35 T), and NMR spectrometers (60 MHz, 400 MHz, and 500 MHz 1H frequencies) in addition to clean room facilities, bio-laboratory space and computing equipment.

IBEC is also part of the Barcelona Institute of Science and Technology (BIST), a scientific foundation of seven of Catalonia’s research centres of excellence (CRG, IBEC, ICFO, ICIQ, ICN2, IFAE, IRB). The mission of BIST is to build new scientific collaborations among these centres, thus giving impulse to multidisciplinary projects to push ever further the frontiers of knowledge. Each BIST centre has reached a high level of excellence in its respective areas of expertise.

Contact: 

For informal inquiries about the position, please contact Dr. Irene Marco-Rius (imarco@ibecbarcelona.eu), Junior Leader fellow, Ramon laboratory, IBEC. 

Interested applicants should send the following materials: (1) a cover letter detailing research interests, (2) a curriculum vitae, (3) letters of recommendation from two referees.

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[NMR] PhD studentship in hyperpolarized 13C NMR #DNPNMR

PhD studentship in hyperpolarized 13C NMR

Barcelona, Spain

A PhD studentship is available starting from January 1st 2020 at the Institute for Bioengineering of Catalonia (IBEC), funded by an EU Horizon 2020 Future Emerging Technologies (H2020 FET-OPEN) grant. 

The project we offer concerns real-time study of metabolism in engineered “organ-on-a-chip” tissue systems via hyperpolarized magnetic resonance. As part of our efforts to create non-invasive platforms for tailored drug testing, the successful candidate will be involved in the development of Carbon-13 hyperpolarization methods, as well as carrying out innovative work on the tissue engineering side of the project. 

This multidisciplinary project is at the interface between physics, chemistry, biochemistry and tissue engineering.

Applicants should have a B.Sc./M.Sc. (or equivalent degree) in engineering, physics, or chemistry. Previous experience in 13C hyperpolarization, magnetic resonance hardware, data acquisition and signal/image processing areas of nuclear magnetic resonance is strongly favored. A knowledge of C++, Matlab, Python, and magnetic resonance spectrometer programming languages, will also be evaluated. Applicants should demonstrate excellent communication skills.

Environment:

The Institute for Bioengineering of Catalonia (IBEC) is a research institute covering most bioengineering fields, from basic research to medical applications. IBEC is located at the Barcelona Science Park (PCB, www.pcb.ub.edu) in central Barcelona, and has strong connections with the nearby Bellvitge University Hospital (BUH). The researcher will have access to a commercial DNP instrument (3.35 T), and NMR spectrometers (60 MHz, 400 MHz, and 500 MHz 1H frequencies) in addition to clean room facilities, bio-laboratory space and computing equipment.

IBEC is also part of the Barcelona Institute of Science and Technology (BIST), a scientific foundation of seven of Catalonia’s research centres of excellence (CRG, IBEC, ICFO, ICIQ, ICN2, IFAE, IRB). The mission of BIST is to build new scientific collaborations among these centres, thus giving impulse to multidisciplinary projects to push ever further the frontiers of knowledge. Each BIST centre has reached a high level of excellence in its respective areas of expertise.

Contact: 

For informal inquiries about the position, please contact Dr. Irene Marco-Rius (imarco@ibecbarcelona.eu), Junior Leader fellow, Ramon laboratory, IBEC. 

Interested applicants should send the following materials: (1) a cover letter detailing their research interests, (2) a curriculum vitae, (3) contact information for two referees.

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[NMR] Postdoc/PhD position in Fluidics for Hyperpolarized Metabolic Magnetic Resonance #DNPNMR

Center for Hyperpolarization in Magnetic Resonance invites applications for a PhD or Post-doc position in Fluidics for Hyperpolarized Metabolic Magnetic Resonance.

Center for Hyperpolarization in Magnetic Resonance (HYPERMAG) is a center of excellence funded by the Danish National Research Foundation. We are part of the Center for Magnetic Resonance (www.cmr.healthtech.dtu.dk) at the department of Health Technology and conduct research in metabolic MRI and NMR. Our research is conducted in collaboration with universities, hospitals and healthcare companies both nationally and internationally. Our main educational responsibility is within the BSc and MSc program in BioMedical Engineering in collaboration with the Faculty of Health Sciences, University of Copenhagen.

Our mission is to address basic scientific questions of hyperpolarization by Dynamic Nuclear Polarization (DNP) to enable new applications of Magnetic Resonance in the study of biochemical reactions in real-time in vivo and in vitro. The group has high-resolution NMR systems of various types (e.g. Agilent, RS2D and Magritek), several polarizers (home-built and Hypersense), a cell lab, chemistry lab and electronics labs. We are 20-25 researchers and support staff.

Responsibilities and tasks

You will be responsible for 

  • The development of a robust sample transfer system between the dDNP polarizer and NMR equipment. With the purpose to reproducibly conduct metabolite identification experiments (fast transfer of bulk samples) and to conduct tracer studies in cell suspension (transfer of substrates and mixing with cells/infusion of hyperpolarized substrate). In particularly to ensure fast, automated and efficient transfer and mixing of the cells with the hyperpolarized substrate.
  • Making the transfer and mixing system compatible with a bioreactor for longitudinal studies of cell cultures.
  • As a PhD student you will further be responsible to apply the integrated transfer, mixing and bioreactor system on specific biological systems.
  • As a Post doc you will be a key collaborator for the biological sub-group of HYPERMAG for the application of the integrated transfer, mixing and bioreactor system to longitudinal studies on various cell lines in other projects.

Qualifications

Candidates should hold a Master (PhD position) or PhD degree (postdoc position) within the field of analytical chemistry or equivalent.

  • Hands on experience with fluidics and mechanics such as HPLC systems
  • Core interest in development of technical solutions for biological research
  • Experience with NMR
  • Experience with cell studies
  • You are driven by pushing boundaries
  • You enjoy working with complex topics
  • You are motivated by both individual and team accomplishment

Approval and Enrolment (only relevant for PhD candidates)

The scholarship for the PhD degree is subject to academic approval, and the candidate will be enrolled in one of the general degree programmes at DTU. For information about our enrolment requirements and the general planning of the PhD study programme, please see the DTU PhD Guide

We offer

DTU is a leading technical university globally recognized for the excellence of its research, education, innovation and scientific advice. We offer a rewarding and challenging job in an international environment. We strive for academic excellence in an environment characterized by collegial respect and academic freedom tempered by responsibility.

Salary and terms of employment

The appointment will be based on the collective agreement with the Danish Confederation of Professional Associations. The allowance will be agreed upon with the relevant union. The PhD position is for 3 years. The postdoc position is for 2 years.

The work place is DTU Lyngby campus.

You can read more about career paths at DTU here

Further information

Further information may be obtained from Prof. Jan Ardenkjær-Larsen, tel.: +45 4525 3918.

You can read more about DTU Health Tech at www.healthtech.dtu.dk/english

Application procedure

Please submit your online application (Postdoc/PhD position in Fluidics for Hyperpolarized Metabolic Magnetic Resonance) no later than 15 September 2019 (local time). Applications must be submitted as one PDF file containing all materials to be given consideration. To apply, please open the link \”Apply online\”, fill out the online application form, and attach all your materials in English in one PDF file. The file must include: 

  • A letter motivating the application (cover letter)
  • Curriculum vitae
  • Grade transcripts and BSc/MSc diploma
  • PhD diploma (if applying for a post-doc position)
  • Excel sheet with translation of grades to the Danish grading system (see guidelines and Excel spreadsheet here – if applying for a PhD position)

Candidates may apply for a PhD position prior to obtaining their master\’s degree but cannot begin before having received it.

Applications and enclosures received after the deadline will not be considered.

All interested candidates irrespective of age, gender, disability, race, religion or ethnic background are encouraged to apply.

Jan Henrik Ardenkjær-Larsen

Professor and Section Head

Center for Magnetic Resonance

Technical University of Denmark 

Department of Health Technology

Ørsted Plads, bldg 349, office 126

DK – 2800 Kgs. Lyngby

Phone +45 45253918

Mobile +45 40272775

jhar@elektro.dtu.dk

hypermag.dtu.dk

cmr.elektro.dtu.dk

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Transport of hyperpolarized samples in dissolution-DNP experiments #DNPNMR

Kiryutin, Alexey S., Bogdan A. Rodin, Alexandra V. Yurkovskaya, Konstantin L. Ivanov, Dennis Kurzbach, Sami Jannin, David Guarin, Daniel Abergel, and Geoffrey Bodenhausen. “Transport of Hyperpolarized Samples in Dissolution-DNP Experiments.” Physical Chemistry Chemical Physics 21, no. 25 (2019): 13696–705.

https://doi.org/10.1039/C9CP02600B

Dissolution dynamic nuclear polarization (D-DNP) experiments rely on the transfer of a sample between two high-field magnets. During this transfer, samples might experience passage through regions where the stray fields of the magnets are very weak, can approach zero, and even change their sign. This can lead to unexpected spectral features in spin systems that undergo transitions from weak- to strong-coupling regimes and vice versa, much like in field cycling nuclear magnetic resonance experiments. We herein demonstrate that the spectral features observed in D-DNP experiments can be rationalized, provided the time-dependence of the spin Hamiltonian upon field cycling is sufficiently adiabatic. Under such conditions, a passage through a weak static field can lead to the emergence of a long-lived state (LLS) based on an imbalance between the populations of singlet and triplet states in pairs of nuclei that are strongly coupled during the passage through low field. The LLS entails the appearance of anti-phase multiplet components upon transfer to a high-field magnet for observation of NMR signals.

Detecting acetylated aminoacids in blood serum using hyperpolarized 13C-1Η-2D-NMR

Katsikis, Sotirios, Ildefonso Marin-Montesinos, Christian Ludwig, and Ulrich L. Günther. “Detecting Acetylated Aminoacids in Blood Serum Using Hyperpolarized 13C-1Η-2D-NMR.” Journal of Magnetic Resonance 305 (August 2019): 175–79.

https://doi.org/10.1016/j.jmr.2019.07.003

Dynamic Nuclear Polarization (DNP) can substantially enhance the sensitivity of NMR experiments. Among the implementations of DNP, ex-situ dissolution DNP (dDNP) achieves high signal enhancement levels owing to a combination of a large temperature factor between 1.4 and 300 K with the actual DNP effect in the solid state at 1.4 K. For sufficiently long T1 relaxation times much of the polarization can be preserved during dissolution with hot solvent, thus enabling fast experiments during the life time of the polarization. Unfortunately, for many metabolites found in biological samples such as blood, relaxation times are too short to achieve a significant enhancement. We have therefore introduced 13C-carbonyl labeled acetyl groups as probes into amino acid metabolites using a simple reaction protocol. The advantage of such tags is a sufficiently long T1 relaxation time, the possibility to enhance signal intensity by introducing 13C, and the possibility to identify tagged metabolites in NMR spectra. We demonstrate feasibility for mixtures of amino acids and for blood serum. In two-dimensional dDNP-enhanced HMQC experiments of these samples acquired in 8 s we can identify acetylated amino acids and other metabolites based on small differences in chemical shifts.

Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts #DNPNMR

Jannin, Sami, Jean-Nicolas Dumez, Patrick Giraudeau, and Dennis Kurzbach. “Application and Methodology of Dissolution Dynamic Nuclear Polarization in Physical, Chemical and Biological Contexts.” Journal of Magnetic Resonance 305 (August 2019): 41–50.

https://doi.org/10.1016/j.jmr.2019.06.001

Dissolution dynamic nuclear polarization (d-DNP) is a versatile method to enhance nuclear magnetic resonance (NMR) spectroscopy. It boosts signal intensities by four to five orders of magnitude thereby providing the potential to improve and enable a plethora of applications ranging from the real-time monitoring of chemical or biological processes to metabolomics and in-cell investigations. This perspectives article highlights possible avenues for developments and applications of d-DNP in biochemical and physicochemical studies. It outlines how chemists, biologists and physicists with various fields of interest can transform and employ d-DNP as a powerful characterization method for their research.

Optimized microwave delivery in dDNP #DNPNMR

Albannay, Mohammed M., Joachim M.O. Vinther, Andrea Capozzi, Vitaliy Zhurbenko, and Jan Henrik Ardenkjaer-Larsen. “Optimized Microwave Delivery in DDNP.” Journal of Magnetic Resonance 305 (August 2019): 58–65.

https://doi.org/10.1016/j.jmr.2019.06.004

Dissolution dynamic nuclear polarization (dDNP) has permitted the production of highly polarized liquid-state samples, enabling real-time imaging of metabolic processes non-invasively in vivo. The desire for higher magnetic resonance sensitivity has led to the development of multiple home-built and commercial dDNP polarizers employing solid-state microwave sources. Providing efficient microwave delivery that avoids unwanted heating of the sample is a crucial step to achieve high nuclear polarization. Consequently, a process is described to reduce waveguide attenuation due to resistive loss thereby doubling the delivered power. A mirror and reflector are designed and tested to increase the microwave field density across the sample volume resulting in a 2.3 dB increase of delivered power. Thermal considerations with regards to waveguide geometry and dDNP probe design are discussed. A thermal model of the dDNP probe is computed and experimentally verified.

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