HyperStore: Singlet states and supercritical fluids for storage and transport of hyperpolarised spin order
Lead Research Organisation:
University of Southampton
Department Name: Sch of Chemistry
Abstract
Nuclear magnetic resonance (NMR) is a versatile analytical tool with applications ranging from basic physics to medicine. In its imaging mode, MRI, it provides information on anatomy, metabolism and biological functions. However, NMR has low sensitivity, making many of its uses difficult and others impossible without some form of signal enhancement. For example, metabolic imaging of human cancer by MRI was only made possible by the recent introduction of nuclear spin hyperpolarisation methods. Among these methods, dissolution dynamic nuclear polarisation (dDNP - central to this proposal) prepare a very high degree of nuclear spin polarisation that can increase the signal-to-noise ratio up to 10,000 times. However, despite this enormous enhancement, in-vivo applications remain on the borderline of feasibility because of the relatively short lifetime of the enhanced polarisation. For example, the spatial resolution of hyperpolarised MRI images of cancer metabolism is compromised by the loss of signal during transport and purification of the hyperpolarised material. Improvements to post-hyperpolarisation protocols, allowing transport of hyperpolarised material, would therefore improve emerging techniques and open up new areas of research and applications.
The proposed research will address three interconnected main obstacles: the lack of purity of the hyperpolarised material (electron radicals are required by the hyperpolarisation technique); the limited lifetime of hyperpolarised magnetisation (the presence of radicals and many other intrinsic factors make nuclear spin polarisation to decay over time, a mechanism know as spin relaxation); the limited mobility of the polarising equipment (dissolution-DNP equipment is expensive and bulky and the limited lifetime of the hyperpolarised agents makes it impossible to transport the agent for significant distances. The point-of-use is therefore confined to the near vicinity of the point-of-production).
In order to overcome these obstacles we will use supercritical-CO2 chromatography to rapidly and efficiently purify the hyperpolarised material. Because spin polarisation storage times are roughly inversely proportional to viscosity, and because supercritical-CO2 has a viscosity 10-30 times lower than that of conventional solvents, we will also store the purified material under supercritical-CO2, potentially extending the length of storage time by 5-10 times. We will then explore extending storage time further by using long-lived states and by freezing the hyperpolarised solution under liquid nitrogen, freezing molecular motion and therefore minimising relaxation losses. We aim to extend storage of hyperpolarised material to over two hours, increasing distance between the point-of-production and the point-of-use. We also intend to build a convenient and portable transport device to enable transport of hyperpolarised material over long distances (as allowed by maximum lifetime achieved) with loss of no more than 50% of polarisation.
The proposed research will address three interconnected main obstacles: the lack of purity of the hyperpolarised material (electron radicals are required by the hyperpolarisation technique); the limited lifetime of hyperpolarised magnetisation (the presence of radicals and many other intrinsic factors make nuclear spin polarisation to decay over time, a mechanism know as spin relaxation); the limited mobility of the polarising equipment (dissolution-DNP equipment is expensive and bulky and the limited lifetime of the hyperpolarised agents makes it impossible to transport the agent for significant distances. The point-of-use is therefore confined to the near vicinity of the point-of-production).
In order to overcome these obstacles we will use supercritical-CO2 chromatography to rapidly and efficiently purify the hyperpolarised material. Because spin polarisation storage times are roughly inversely proportional to viscosity, and because supercritical-CO2 has a viscosity 10-30 times lower than that of conventional solvents, we will also store the purified material under supercritical-CO2, potentially extending the length of storage time by 5-10 times. We will then explore extending storage time further by using long-lived states and by freezing the hyperpolarised solution under liquid nitrogen, freezing molecular motion and therefore minimising relaxation losses. We aim to extend storage of hyperpolarised material to over two hours, increasing distance between the point-of-production and the point-of-use. We also intend to build a convenient and portable transport device to enable transport of hyperpolarised material over long distances (as allowed by maximum lifetime achieved) with loss of no more than 50% of polarisation.
Planned Impact
Societal Impact. The proposed research aims to extend the lifetime of hyperpolarised material, and improve methods for handling it. Hyperpolarised material generates substantially enhanced NMR/MRI signals (by over 10,000 times) and is important in a variety of areas such as materials science, catalysis and clinical medicine. Human clinical trials conducted in the USA showed that hyperpolarised NMR can be used to characterize cancer in a way that is inaccessible to other methods. Cheaper and more widespread use of such technology may lead to early detection of cancer and better characterisation of its response to treatment. Consequently, new modalities may increase treatment efficacy while reducing cost.
It is also important to have an informed society, and we will use the internet as a rapid, worldwide medium to maximise dissemination. In addition, the University scientific press will be used to communicate crucial developments to the non-expert public. Finally, we will disseminate our results using scientific video journals, a new format that is direct and user-friendly.
Economic Impact. There is a good chance that the engineering and methodological parts of this project will give rise to IP that may be the basis for a new start-up company; especially if hyperpolarised material lifetimes are long enough to allow the material to be generated at a central site (possibly a company) and transported to the point-of-use in the hyperpolarised state (similar to PET, which uses centralized "hot lab" production). We will work in coordination with the Research and Innovation Services (RIS) and the IP team at the University of Southampton to explore the possibility of patent filing, engage with industries and setup a start-up company.
It is also important to have an informed society, and we will use the internet as a rapid, worldwide medium to maximise dissemination. In addition, the University scientific press will be used to communicate crucial developments to the non-expert public. Finally, we will disseminate our results using scientific video journals, a new format that is direct and user-friendly.
Economic Impact. There is a good chance that the engineering and methodological parts of this project will give rise to IP that may be the basis for a new start-up company; especially if hyperpolarised material lifetimes are long enough to allow the material to be generated at a central site (possibly a company) and transported to the point-of-use in the hyperpolarised state (similar to PET, which uses centralized "hot lab" production). We will work in coordination with the Research and Innovation Services (RIS) and the IP team at the University of Southampton to explore the possibility of patent filing, engage with industries and setup a start-up company.
Publications
Elliott SJ
(2019)
Nuclear singlet relaxation by scalar relaxation of the second kind in the slow-fluctuation regime.
in The Journal of chemical physics
Hall AMR
(2020)
A temperature-controlled sample shuttle for field-cycling NMR.
in Journal of magnetic resonance (San Diego, Calif. : 1997)
Melchiorre G
(2021)
Single-scan measurements of nuclear spin singlet order decay rates.
in Physical chemistry chemical physics : PCCP
Moysiadi A
(2021)
Nuclear Spin Relaxation of Longitudinal and Singlet Order in Liquid-CO2 Solutions.
in Frontiers in chemistry
Sheberstov KF
(2019)
Excitation of singlet-triplet coherences in pairs of nearly-equivalent spins.
in Physical chemistry chemical physics : PCCP
Stevanato G
(2017)
A pulse sequence for singlet to heteronuclear magnetization transfer: S2hM.
in Journal of magnetic resonance (San Diego, Calif. : 1997)
Description | We have demonstrated it is indeed possible to store spin polarisation in supercritical fluids prolonghing its lifetime by a factor of about 5. This is the factor we have conservatively predicted in the proposal. We intended to explore what were the limitations to this factor and how to overcome them, but the research has been impacted by Covid and these experiments could not been run. |
Exploitation Route | The main applications of these finding is in the storage of hyperpolarisation for long times and in its use in sites which are distant in time and/or space from its production site. In the long-term this can be used to prepare hyperpolarised MRI contrast agents that can be delivered to other laboratories or clinics to be used in MRI scans and experiments. |
Sectors | Chemicals Healthcare Other |
Description | Member of the Management Board of the Italian NMR society (2016-2019) |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
URL | http://www.gidrm.org |
Description | Member of the Management Board of the Italian NMR society (2020-2023) |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
URL | http://www.gidrm.org |
Description | Membership of the Management Committee of an European COST Action (2017-2021) |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
URL | http://eurelax.uwm.edu.pl |
Description | PhD CASE Studentship |
Amount | £90,000 (GBP) |
Organisation | Bruker Corporation |
Sector | Private |
Country | United States |
Start | 09/2018 |
End | 09/2022 |
Description | Platform Grant |
Amount | £1,784,689 (GBP) |
Funding ID | EP/P009980/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2017 |
End | 02/2022 |
Title | Temperature controlled sample shuttle |
Description | We have built a world-unique temperature controlled sample shuttle that transport the sample at any desired field between 7 T and 50 mT while keeping the sample temperature stable within 0.05 K. The sample accepts standard 5mm tubes as well as high pressure zirconia/sapphire 5mm tubes |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | The tool was developed for this project since we aimed to measure the relaxation properties of samples dissolved in liquid and supercritical CO2 and this material is prone to thermal convection meaning that a precise control of temperature while the sample was moving to different magnetic field was necessary. This same tool is able to measure convection compensated diffusion coefficients and can be deployed in whatever experiment where thermal convection is a limiting factor. We have offered access to such tool as part of the NMR facility at the University of Southampton and listed the availability for use through the Connect NMR network. We have already received a visit from a researcher from the university of Turin who collected some data on pyruvate relaxation at different field to be used within their project. |
Description | Methods for manipulating long-lived states |
Organisation | Russian Academy of Sciences |
Department | International Tomography Center |
Country | Russian Federation |
Sector | Public |
PI Contribution | We contributed with samples and ideas on the theory beyond the topic |
Collaborator Contribution | They props the main idea, run the experiments, workout the theory |
Impact | We published a paper together and we are working on another one and a few more ideas |
Start Year | 2017 |
Title | A filling station for high pressure NMR tube |
Description | We designed and build a filling station able to fill high-pressure NMR tubes (0-300bar) monitoring the final pressure, the amount of gas added and removing H2O and O2 traces. |
Type Of Technology | Systems, Materials & Instrumental Engineering |
Year Produced | 2018 |
Impact | This tool is essential to this project as allow us to explore the lifetime of substances dissolved in liquid and supercritical fluids (CO2 in particular in this project) |
Title | A sample shuttle for field cycled experiments |
Description | We designed and built a sample shuttle that allows us to run NMR experiments at various values of the magnetic field using the stray field of the NMR magnet itself. |
Type Of Technology | Systems, Materials & Instrumental Engineering |
Year Produced | 2019 |
Impact | This kit allows peculiar experiments to be run such as measuring the field dependence of the relaxation time decay of substances which has relevance in many field from food to medicine. We were already approached by a group who intend to do experiments on this device and a researcher from that laboratory has been invited to spend 4 weeks in my laboratory in June 2019 to run such experiments. |
Title | A viscometer for supercritical fluids |
Description | We have designed and built a rolling-ball viscometer able to measure the viscosity of liquids and gases pressurised up to 300 bar. Measurements can be done in the range 20-45 degrees. |
Type Of Technology | Systems, Materials & Instrumental Engineering |
Year Produced | 2018 |
Impact | The instrument has been developed specifically to measure the viscosity of liquid and supercritical CO2 mixtures for which, to our knowledge, there is no commercial product available to date. |
Description | An invited talk at the University of York |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | I was invited to give a talk for the Department of Chemistry, Centre for Hyperpolarised Magnetic Resonance on latest developments relative to this project. About 50 people attended the talk which was delivered in video call because of Covid-related restriction. After the talk we engaged in a private discussion with the director and other senior member of the magnetic resonance group for setting up possible future collaboration. We are right now trying to modify our methodology to accommodate some developments done in York. This could lead to further research directions. |
Year(s) Of Engagement Activity | 2020 |
Description | Contributed Talk at major NMR conference (EUROMAR 18 - Pileio) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Contributed Talk on "HyperStore: Towards storage and remote transport of (hyper)polarised order via supercritical fluids" at the international major conference EUROMAR in Nantes, France, July 2018 |
Year(s) Of Engagement Activity | 2018 |
Description | Departmental Talk (UoS 19 - Giustiniano) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Talk on Measurement of viscosity of liquid and supercritical CO2 for the Magnetic Resonance Section of the Chemistry Department at the University of Southampton |
Year(s) Of Engagement Activity | 2019 |
Description | Departmental Talk (UoS 20 - Giustiniano) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Talk on Measurement of density of liquid and supercritical CO2, and other liquids, for the Magnetic Resonance Section of the Chemistry Department at the University of Southampton |
Year(s) Of Engagement Activity | 2020 |
Description | Departmental Talk (UoS 20 - Hall) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Talk on HyperStore developments for the Magnetic Resonance Section of the Chemistry Department at the University of Southampton |
Year(s) Of Engagement Activity | 2020 |
Description | Invited Talk at international conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I was invited to give a talk at the PERM 2020 meeting (parahydrogen enhanced resonance meeting) where I discussed about some of the outcomes of this project and their possible applications in the field of hyperpolarization. The talk stimulated a lot of interest and I was invited to submit a paper for a special issue of Chem Phys Chem journal. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.perm-conference.org/perm2020/program |
Description | Poster at the national meeting of the Italian NMR society (GIDRM 17 - Moysiadi) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A poster was presented during the poster session of an international meeting of the Italian NMR discussion group. It generate attention and questions by peers and it was voted second at the best poster competition although only first price was formally attributed. |
Year(s) Of Engagement Activity | 2017 |
Description | Southampton Science and Engineering Festival - 2019 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | We were running a live demonstration of how an MRI scan is taken having as "patient" a gummy bear which we implanted with a plastic heart and a little fish in the stomach. During the demonstration, primarily addressed to families with children, we discussed how NMR and MRI work, showed how we could see inside the gummy bear to check if they have a heart and what the have eaten and then discussed with the older audience what we actually do with the technique and the current funded projects. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.sotsef.co.uk |
Description | Southampton University Open days 2019 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | We were running a live demonstration of how an MRI scan is taken having as "patient" Homer Simpson (a jelly sample) which we implanted with a plastic doughnut and a beer bottle in the stomach. During the demonstration we discussed how NMR and MRI work, showed how we could see inside a patient to diagnose illnesses and then discussed with what we actually do with the technique and the current funded projects. |
Year(s) Of Engagement Activity | 2019 |