A Multidisciplinary Research Platform for Nuclear Spins far from Equilibrium

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry

Abstract

Nuclear Magnetic Resonance (NMR) is a technique which uses the fact that the nuclei of many atoms act as tiny radiotransmitters, emitting radio signals at precisely-defined frequencies, which can be detected by a carefully-tuned detector. In an NMR experiment, the nuclei are first magnetised by placing a sample in a strong magnetic field for some time. A sequence of radiofrequency pulses is then applied to the sample, which subsequently emits radiowaves which are detected in the radio receiver. The pattern of emitted waves provides information on the chemical composition and spatial distribution of the sample.

Magnetic nuclei may be viewed as small bar magnets, which may point in any direction in space. In normal circumstances the directions in which the nuclear magnets point are almost uniformly distributed, meaning that all directions are almost equally likely. As a result the net nuclear magnetism almost completely cancels out. However, when a strong magnetic field is applied, there is a very small change in this distribution, so that slightly more nuclei point along the applied field, than opposite to it. A very small net magnetism is developed along the applied field, and this is used to generate NMR and MRI signals.

It is possible to generate materials with strongly perturbed nuclear spin distributions. There are two different types of non-equilibrium nuclear spin states.

In the first type, the nuclei are strongly lined up in one direction, to a degree which is much greater than that which is available without intervention. Such materials are said to be hyperpolarized. Materials in hyperpolarized states can generate NMR signals which are 100000 stronger than normal. This phenomenon has already been used in clinical trials for the detection of cancer in human patients.

In the second type of non-equilibrium spin state, neighbouring nuclei in the same molecule are strongly aligned with other, as opposed to being aligned along an external direction. In sufficiently symmetrical molecules, this leads to the phenomenon of spin isomerism, in which compounds with different nuclear spin configurations behave as separate physical substances, which can be stable for a long time. The seminal case is hydrogen gas (H2) where the spin isomers are called ortho and parahydrogen. These spin isomers were predicted to exist by Heisenberg (for which he was awarded a Nobel prize) and their existence is one of the triumphs of quantum mechanics. Recently our group showed that ordinary water may also exhibit ortho and para spin isomers, providing the water molecules are trapped inside carbon cages (fullerenes) so that they are free to rotate at low temperature. We also showed that the type of water spin isomer has an influence on the electrical properties of the material.

In this Platform Grant we will further develop the sciences of hyperpolarization and spin isomerism and explore how they relate to each other. In some circumstances, spin isomerism may lead to hyperpolarization, and vice versa. By conducting this research we will learn a great deal about the behaviour of magnetic nuclei in symmetrical molecules, and develop new methods for enhancing NMR signals by enormous factors, which will have an impact on a wide range of sciences, including clinical medicine and the detection and characterisation of cancer.

The new science of materials in nuclear spin states which are far from equilibrium also offers commercial opportunities in the form of novel MRI (magnetic resonance imaging) technology, and hyperpolarized imaging agents.

During the project we will give our research team the opportunity to work flexibly and interactively across several interlocking disciplines. An innovation fund with an internal bidding process will be instituted to allow the participating researchers to explore their own ideas and to visit other laboratories.

Planned Impact

1. Academic impact

1.1 New knowledge and scientific advancement.
The research in this proposal is fundamental in nature. How are materials generated with highly non-equilibrium nuclear spin states? How may such states be maintained for significant times? What materials phenomena are associated with highly non-equilibrium nuclear spin states? How can such phenomena be exploited in NMR and other fields such as medicine, biochemistry, materials science and superconductivity?

The proposal is highly interdisciplinary involving organic and inorganic chemistry, quantum physics, materials science, biochemistry, cryogenics and imaging.

1.2 Worldwide scientific advancement
The proposal is part of an ongoing direct collaboration with project partners from Estonia, Denmark and France. In addition the participating groups have close collaborations with research groups in Germany, Greece, Sweden, Japan, India, Australia and USA.

1.3 Development of new methodologies, equipment, techniques, cross-disciplinary approaches.
The project uses multiple new methodologies, equipment and techniques. The project is highly cross-disciplinary, involving chemistry, quantum physics, imaging, biochemistry, and reaches out into clinical medicine.

1.4 Delivering and training researchers.
The named researchers will be given the opportunity to lead their project packages and to train as a research leader of the future. We will mentor these young researchers into future academic leadership roles.

2. Economic and Societal Impact

2.1 Societal benefits. The research described here is directed towards the development of enhanced imaging modalities, of potentially great benefit to the diagnosis and treatment of a wide range of diseases, especially early detection of cancer and better characterisation of its response to treatment. These new modalities can therefore considerably increase the efficacy of treatments while reducing cost. In addition some projects under this platform will develop techniques which have the potential for improving energy materials.

Science is a cultural activity - especially basic science. Basic research of this nature is therefore culturally enriching.

2.2 Economic benefits. Magnet technology is a strength of UK engineering so enhancements in NMR and MRI are of long-term economic benefit to the UK. In particular Oxford Instruments has invested heavily in HYPERSENSE technology so that advances in this technology are very important for that key company. Cryogenic and Thomas Keating are other UK companies with a heavy investment in advanced magnetic resonance technology. GE also has facilities located in the UK. The technologies developed in this project may underpin new startup companies: for example new devices for producing hyperpolarized materials, or compounds which may be prepared and transported in a hyperpolarized state, and better and more transportable MRI systems.

Improved efficiency in the treatment of diseases such as stroke and cancer will reduce the cost burden on health services.

The training of researchers in advanced NMR and MRI techniques and their associated theory will equip UK industry to compete better in these areas in the future, bringing further economic benefits. Even if researchers on this grant end up in different fields, their experience of the highly interdisciplinary environment in this project will equip them well to conduct and lead interdisciplinary and flexible activities in the future.

Organisations

Publications

10 25 50
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Alonso-Valdesueiro J (2018) Testing signal enhancement mechanisms in the dissolution NMR of acetone. in Journal of magnetic resonance (San Diego, Calif. : 1997)

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Bengs C (2018) SpinDynamica: Symbolic and numerical magnetic resonance in a Mathematica environment. in Magnetic resonance in chemistry : MRC

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Bengs C (2020) A master equation for spin systems far from equilibrium in Journal of Magnetic Resonance

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Bloodworth S (2019) First Synthesis and Characterization of CH 4 @C 60 in Angewandte Chemie

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Bloodworth S (2019) First Synthesis and Characterization of CH @C. in Angewandte Chemie (International ed. in English)

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Bloodworth S (2018) Synthesis and Properties of Open Fullerenes Encapsulating Ammonia and Methane. in Chemphyschem : a European journal of chemical physics and physical chemistry

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Brown LJ (2017) Synthesis of carbon-13 labeled oxalates exhibiting extended nuclear singlet state lifetimes. in Journal of labelled compounds & radiopharmaceuticals

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Dumez JN (2017) Dynamic Nuclear Polarization of Long-Lived Nuclear Spin States in Methyl Groups. in The journal of physical chemistry letters

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Eills J (2018) Preservation of Nuclear Spin Order by Precipitation. in Chemphyschem : a European journal of chemical physics and physical chemistry

 
Description Samples may be prepared in highly non-equilibrium nuclear spin states. These states can give rise to highly enhanced nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) signals. We are learning how to prepare such states and how to understand their behaviour.
Exploitation Route Enhancement of knowledge.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology,Other

 
Description European Research Council Advanced Grant
Amount € 2,762,223 (EUR)
Funding ID 786707 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 10/2018 
End 09/2023
 
Description HyperStore: Singlet states and supercritical fluids for storage and transport of hyperpolarised spin order
Amount £557,185 (GBP)
Funding ID EP/P005187/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 12/2016 
End 11/2019
 
Description Marie Sklodowska-Curie Innovative Training Networks
Amount € 2,794,786 (EUR)
Funding ID 766402 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 02/2018 
End 01/2022
 
Description SINGLET-DIFFUSION-NMR TO PROBE TRANSLATIONAL DYNAMICS IN POROUS MEDIA
Amount £100,978 (GBP)
Funding ID EP/N033558/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 02/2018
 
Description Underpinning Equipment
Amount £1,999,999 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2018
 
Title Bullet-DNP equipment 
Description Device and control system for rapid dissolution of a solid polarized by dynamic nuclear polarization 
Type Of Material Improvements to research infrastructure 
Year Produced 2019 
Provided To Others? Yes  
Impact Research insights and advances 
 
Title Cryogenic NMR probe 
Description Equipment for performing NMR at cryogenic temperatures 
Type Of Material Improvements to research infrastructure 
Year Produced 2015 
Provided To Others? No  
Impact Advances in scientific understanding from measurement results 
 
Title SpinDynamica software 
Description SpinDynamica software is a Mathematica-based system for analyzing, understanding, and simulating nuclear spin dynamics, with applications to NMR and MRI. 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact Widespread use in the NMR community 
URL http://www.spindynamica.soton.ac.uk/
 
Description CH2D collaboration 
Organisation National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS)
Country France 
Sector Academic/University 
PI Contribution NMR theory, measurements and methodology
Collaborator Contribution NMR theory, measurements and methodology. Quantum chemistry collaborations.
Impact see grant entries.
Start Year 2016
 
Description CH2D collaboration 
Organisation Pomona College
Country United States 
Sector Academic/University 
PI Contribution NMR theory, measurements and methodology
Collaborator Contribution NMR theory, measurements and methodology. Quantum chemistry collaborations.
Impact see grant entries.
Start Year 2016
 
Description Endofullerene consortium starting 2015 
Organisation Institut Laue–Langevin
Country France 
Sector Academic/University 
PI Contribution NMR & theory
Collaborator Contribution multidisciplinary research and measurements
Impact Numerous outputs. See linked grants. Multidisciplinary: chemistry, physics
Start Year 2015
 
Description Endofullerene consortium starting 2015 
Organisation Institute of Electronics Microelectronics and Nanotechnology
Country France 
Sector Academic/University 
PI Contribution NMR & theory
Collaborator Contribution multidisciplinary research and measurements
Impact Numerous outputs. See linked grants. Multidisciplinary: chemistry, physics
Start Year 2015
 
Description Endofullerene consortium starting 2015 
Organisation Jagiellonian University
Department Jagiellonian University Medical College
Country Poland 
Sector Academic/University 
PI Contribution NMR & theory
Collaborator Contribution multidisciplinary research and measurements
Impact Numerous outputs. See linked grants. Multidisciplinary: chemistry, physics
Start Year 2015
 
Description Endofullerene consortium starting 2015 
Organisation Johannes Gutenberg University of Mainz
Country Germany 
Sector Academic/University 
PI Contribution NMR & theory
Collaborator Contribution multidisciplinary research and measurements
Impact Numerous outputs. See linked grants. Multidisciplinary: chemistry, physics
Start Year 2015
 
Description Endofullerene consortium starting 2015 
Organisation National institute of Chemical Physics, Tallinn
Country Estonia 
Sector Academic/University 
PI Contribution NMR & theory
Collaborator Contribution multidisciplinary research and measurements
Impact Numerous outputs. See linked grants. Multidisciplinary: chemistry, physics
Start Year 2015
 
Description Endofullerene consortium starting 2015 
Organisation University of Nottingham
Department School of Psychology Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution NMR & theory
Collaborator Contribution multidisciplinary research and measurements
Impact Numerous outputs. See linked grants. Multidisciplinary: chemistry, physics
Start Year 2015
 
Description Endofullerenes as laser materials 
Organisation Institute of Electronics Microelectronics and Nanotechnology
Country France 
Sector Academic/University 
PI Contribution Materials, theory, concepts
Collaborator Contribution Experiments, concepts, materials
Impact none yet
Start Year 2019
 
Description Field-cycling investigations of long-lived nuclear spin states 
Organisation Russian Academy of Sciences
Department International Tomography Center
Country Russian Federation 
Sector Public 
PI Contribution Samples, ideas, spin dynamical expertise
Collaborator Contribution Equipment, personnel, spin dynamical expertise
Impact Publications listed under grants
Start Year 2018
 
Description Hyperpolarization collaboration 
Organisation Cambridge Cancer Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation Swiss Federal Institute of Technology in Lausanne (EPFL)
Country Switzerland 
Sector Public 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation University of Copenhagen
Country Denmark 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation University of Pennsylvania
Country United States 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation École normale supérieure de Lyon (ENS Lyon)
Country France 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarized 3He NMR 
Organisation Jagiellonian University
Country Poland 
Sector Academic/University 
PI Contribution samples, background knowledge, ideas
Collaborator Contribution 3He NMR and MRI
Impact none yet
Start Year 2018
 
Description Infrared and THz spectroscopy of endofullerenes 
Organisation Institute of Electronics Microelectronics and Nanotechnology
Country France 
Sector Academic/University 
PI Contribution Provision of samples, theory, numerical simulations
Collaborator Contribution Terahertz and infrared spectroscopy, and their interpretation
Impact Numerous outputs listed under associated grants in ResearchFish
Start Year 2015
 
Description Infrared and THz spectroscopy of endofullerenes 
Organisation National Institute of Chemical Physics and Biophysics
Country Estonia 
Sector Academic/University 
PI Contribution Provision of samples, theory, numerical simulations
Collaborator Contribution Terahertz and infrared spectroscopy, and their interpretation
Impact Numerous outputs listed under associated grants in ResearchFish
Start Year 2015
 
Description Neutron scattering of endofullerenes 
Organisation Institut Laue–Langevin
Country France 
Sector Academic/University 
PI Contribution Provision of samples, concepts, and theoretical expertise
Collaborator Contribution PhD studentship; instrument time; expert help; accommodation and substistence
Impact Numerous publications; listed under associated grants in` ResearchFish.
Start Year 2015
 
Description Theory and investigations of nuclear spin isomer conversion (especially in water) 
Organisation National institute of Chemical Physics, Tallinn
Country Estonia 
Sector Academic/University 
PI Contribution Experimental results, theory
Collaborator Contribution Theory, interpretation
Impact none yet
Start Year 2019
 
Description Theory and investigations of nuclear spin isomer conversion (especially in water) 
Organisation Russian Academy of Sciences
Country Russian Federation 
Sector Public 
PI Contribution Experimental results, theory
Collaborator Contribution Theory, interpretation
Impact none yet
Start Year 2019
 
Description ZULF consortium 
Organisation Claude Bernard University Lyon 1 (UCBL)
Department Astrophysics Research Centre of Lyon (CRAL)
Country France 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description ZULF consortium 
Organisation Italian Institute of Technology (Istituto Italiano di Tecnologia IIT)
Country Italy 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description ZULF consortium 
Organisation Jagiellonian University
Country Poland 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description ZULF consortium 
Organisation Johannes Gutenberg University of Mainz
Country Germany 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description ZULF consortium 
Organisation University of Cambridge
Department Cambridge Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description ZULF consortium 
Organisation University of Turin
Department Molecular Imaging Center
Country Italy 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description ZULF consortium 
Organisation University of Ulm
Department Department of Dermatology and Allergic Diseases
Country Germany 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description ZULF consortium 
Organisation University of York
Department York Environmental Sustainability Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Theory, simulations, NMR methodology
Collaborator Contribution Collaborative research
Impact publication DOIs: 10.1016/j.jmr.2019.106645 10.1039/C8CC06636A 10.1063/1.5089486
Start Year 2017
 
Description dDNP collaboration 
Organisation Technical University of Denmark
Country Denmark 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Description dDNP collaboration 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Description dDNP collaboration 
Organisation École Normale Supérieure, Paris
Country France 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Description dDNP collaboration 
Organisation École normale supérieure de Lyon (ENS Lyon)
Country France 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Title SpinDynamica 
Description Large set of Mathematica packages for analyzing, simulating, and understanding NMR experiments. 
Type Of Technology Software 
Year Produced 2017 
Impact widely used in NMR community 
URL http://www.spindynamica.soton.ac.uk