SINGLET-DIFFUSION-NMR TO PROBE TRANSLATIONAL DYNAMICS IN POROUS MEDIA

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

Abstract

Diffusion-NMR is a powerful technique with applications that span from material science to medicine. With the characteristic non-invasiveness and non-harmfulness of Nuclear Magnetic Resonance (NMR), the technique can infer information on molecular diffusion in various media. Diffusion-NMR has applications that range from analytic sciences where it can be used for example to sort out complex molecular mixtures according to different diffusion coefficients up to medicine where it is used to obtain contrast between biological tissues within which molecules have different diffusion properties.
Porous media, which are ubiquitous in nature with examples including rocks, bones, wood etc. are perhaps the most suitable systems to be characterised through diffusion-NMR. And indeed scientific literature contains numerous examples of such investigations. However, because conventional NMR signals last typically for only up to a few seconds, diffusion-NMR studies have some limitations. The measurements of diffusion are done on a microscopic level by registering the changes in the intensity of an NMR signal as molecules diffuse in solution. The longer the diffusion time the farther the molecules diffuse, so that the the registered change in signal is more dramatic and the more accurate the measurement.
Molecular diffusion is affected by the microscopic structure of the material a molecule diffuses within, therefore diffusion-NMR is a very sensitive tool to probe micro-structures, hence its great utility in porous media investigations. However its sensitivity to dimensions is directly linked to the timescale explored i.e. to the available diffusion time. Limitations to diffusion time due to the lifetime of conventional NMR signals therefore restrict the technique to geometries within 100 micrometers. Since many interesting porous structures have pore larger than 100 micrometers the technique cannot probe pore connectivity in those systems hence cannot provide a measure of tortuosity which is of instrumental importance in many areas including oil engineering and battery development.
In the past 10 years I have been investigating the topic of long-lived spin states which are particular configurations of nuclear spin states displaying very long lifetimes that can reach in some cases even an hour length. This lifetime extension can be used in diffusion-NMR to prolong the diffusion time and obtain a better accuracy in diffusion measurement plus the possibility to access information on pore connectivity and hence measure tortuosity.
This proposal deals with the development and assessment of methodology that exploit long-lived states to expand the accessible diffusion time in diffusion-NMR experiments thus giving access to measurement of tortuosity, macroscopic compartmentation and diffusion anisotropy in porous media. The main outcomes of this research are:
1. molecular probes of diffusion that support long-lived states to give access to very long diffusion times
2. NMR methodology to measure diffusion by encoding positional information on long-lived spin states
3. a simulation procedure for simulation of complex NMR experiments on porous systems
4. measurements of tortuosity, anisotropic diffusion and macrostructures in porous media

The proposed methodology is expected to benefit laboratories and industries with interests in characterising porous material and/or developing new materials (an increase in the tortuosity of lithium batteries' electrodes during electrochemical cycling is thought to be partially responsible for the observed reduction of performances, for example). Diffusion anisotropy is of particular interest in MRI where it is exploited in diffusion-tensor-imaging, a technique that uses diffusion anisotropy to map the direction of fibres in the body: methods and procedures developed in this project have the potential to impact this area too.

Planned Impact

Societal. The research described here consists of developing and testing new methodology that could be applied to characterise materials of instrumental importance in our society (batteries, petrol reservoirs, nonwovens, biological tissues). These characterisations can lead, in the medium-long term, to improved materials with an impact on society in terms of cost effective material, new technologies and so on. Possible future translation of this research in the field of clinical MRI could have an impact (in the very long-term) on public health in terms of improved diagnostic techniques. Giving the limited amount of time and funds allowed by this scheme, societal impact has to be put in the long-term frame. Nevertheless it will be endeavoured through publication on personal and institutional websites as well as articles in local newspapers which will be done in collaboration with the University of Southampton Media Relations staff.

Economic. Porous media are ubiquitous and have important applications spanning from material science to medicine. The characterisation of tortuosity and anisotropic diffusion is important information for the design of new material like improved battery components, insulators, super capacitors etc. The methodology described here will contribute to equipping UK industry to compete better in these areas in the future, bringing further economic benefits. However because of the fundamental nature of this research and the limited resources in terms of funds and time, impact on the economy will be a longer-term aim beyond the lifetime of the grant. Nevertheless possibilities of engagement with industry will be explored during this project through i) discussions with industry representatives at conferences and other public events; ii) by chasing collaboration with colleagues to translate methodology in the relevant industrial areas and iii) by exploiting the possibility of patent filing in coordination with Research and Innovation Services (RIS) and the IP team at the University of Southampton.
 
Description As promised in the originally proposed objectives we have delivered a new NMR methodology able to measure diffusion by encoding positional information on long-lived spin states. Such method has given unprecedented access to measurements of tortuosity in model porous media. The development of the NMR methodology was accompanied by the development of simulation procedures based on spin dynamics, monte carlo sampling and molecular dynamics for the simulation of complex NMR experiments on porous systems. We have demonstrated in a publication how such methods can extend the capabilities of NMR in measuring microstructures in opaque samples by showing the direct measurement of cavities of up to 2 millimetre to be compared to 100-200 microns as with previous (more conventional) NMR diffusion techniques. Furthermore we show how the technique can measure the tortuosity of model porous media with pores of up to hundreds of microns, which was previously impossible. We are now working on (and planning to ask for more funds for) applying these methods to samples of more direct impact to science and society like fuel cells and cell scaffolding for tissue engineering.
Exploitation Route The methods developed are general and use standard NMR hardware so that they can be implemented in any NMR laboratory. They are of particular interest for the research groups that investigate the structural properties and the translational dynamics in porous media as well as those interested in molecular diffusion. Material scientists who have no direct access to NMR machine can still profit from the outcome of this grant by referring to NMR research groups which specialise in NMR applied to materials.
Sectors Agriculture, Food and Drink,Energy,Healthcare,Manufacturing, including Industrial Biotechology

 
Description The successful development of the technique described in this grant has allowed, as promised, to break the current limitation of diffusion NMR as described in several papers resulted from this work. While a non-academic impact is not yet tangible, this research has nucleated new research fields. For example, this PI has now running a project funded by the Leverhulme Trusts where the outcomes of this research are exploited in cell cultures grown on 3D-printed scaffoldings where the diffusion techniques enabled by this EPSRC grant are used to understand some structural properties of the scaffoldings and the tissue grown on it. This latter project has, in turn, generated new ideas of using these scaffoldings and techniques to assess the metabolic response to drug treatments.
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
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 DTP PhD Studentship funds
Amount £66,000 (GBP)
Organisation University of Southampton 
Sector Academic/University
Country United Kingdom
Start 01/2019 
End 12/2022
 
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
 
Description Theory and Methodology for Nuclear Spins Diffusing in Porous Media
Amount £280,000 (GBP)
Funding ID RPG-2019-298 
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2020 
End 03/2023
 
Title SAD-NMR 
Description The grant supported the development of the Singlet Assisted Diffusion NMR methodology which consists essentially in a combination of radiofrequency and magnetic field gradient pulses able to extend the capability of diffusion NMR by an order of magnitude or more. Such technique, for instance, gives unprecedented access to measurements of tortuosity in porous media or access to very slow diffusion coefficients (more than an order of magnitude than previously possible with NMR). Additionally, it poses the basis for further developments in diffusion tensor imaging, a technique used in clinical practice to track fibre orientation in the brain and in other contexts. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact too early to generate direct impact as any new method needs to be learned, understood and implemented to a specific problem. Nevertheless a group at the Queensland University of Technology in Australia has recognised the method as able to solve some problem they have with samples made by cells grown on a 3D printed scaffolding for tissue engineering and has therefore asked to engage into a collaboration that we have already activated and also proposed to be formally supported by a new EPSRC grant under submission in Feb 2018. 
 
Description Imaging of chia seed in soils 
Organisation University of Southampton
Department Faculty of Engineering and the Environment
Country United Kingdom 
Sector Academic/University 
PI Contribution We run images of samples containing chia seed in various soils (nation, quartz etc) to study the gel formation around the seeds
Collaborator Contribution partner provided the seeds, the soils and complementary micro-CT images plus the expertise on soil science
Impact An invited paper has been submitted to Frontiers in Environmental Science, section Soil Processes
Start Year 2017
 
Description Measuring tortuosity of cell scaffolding for tissue engineering 
Organisation Queensland University of Technology (QUT)
Country Australia 
Sector Academic/University 
PI Contribution We were and are measuring the tortuosity of 3D printed cell scaffolding for tissue engineering by using the SAD-NMR technique developed under this grant.
Collaborator Contribution Our partners have 3D printed the scaffolding with their own developed technique and have grown cells on the scaffolding
Impact The collaboration is multidisciplinary involving engineering, bio-chemistry, medicine and physical chemistry (NMR and MRI). The collaboration resulted in a pile of data which represent the unprecedented measure of tortuosity in these systems. These data are being complemented with other experiments to be published very soon.
Start Year 2017
 
Description Measuring tortuosity of cell scaffolding for tissue engineering 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution We used the scaffoldings provided by our partners and use these data as benchmark to validate our newly developed NMR technique of singlet assisted diffusion tensor imaging
Collaborator Contribution Our partners provided 3D printed plastic scaffolding samples and relative expertise
Impact This collaboration helped us validating some new developments and it is continuing with the purpose of measuring cells growing on such scaffoldings
Start Year 2020
 
Description A contributed talk at the national meeting of the Italian NMR society (GIDRM 17 - Tourell) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact During the talk there was good interest on the matter and as a result of that we discussed a possible collaboration with a group in Milan.
Year(s) Of Engagement Activity 2017
 
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 international conference (GIDRM 19 - Melchiorre) 
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 SAD-TI: Singlet-assisted diffusion tensor imaging
Year(s) Of Engagement Activity 2019
 
Description Contributed talk at major NMR Conference (EUROMAR 17 - Pileio) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A contributed talk to a major international NMR conference (EUROMAR2017). The conference hosts ~1000 between scientists and NMR industry representatives. There was good interest on the subject with a few question asked directly after the talk and several more afterwards. In particular we engaged into possible collaboration with at least 3 research groups europe-wide.
Year(s) Of Engagement Activity 2017
 
Description Departmental Talk (UoS 17 - Tourell) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact The latest results of this research was discussed in a departmental talk with the purpose to disseminate our results within the chemistry department.
Year(s) Of Engagement Activity 2017
 
Description Departmental Talk (UoS 19 - Melchiorre) 
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 singlet-assisted diffusion tensor imaging for the Magnetic Resonance Section of the Chemistry Department at the University of Southampton
Year(s) Of Engagement Activity 2019
 
Description Invited Talk at National Conference (IOP 19 - Pileio) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact An invited talk to the annual national meeting of the BRSG group of the Institute Of Physics; Title: "SAD-NMR: Singlet Assisted Diffusion NMR to study porous media", IOP/BRSG Meeting, London, UK, 11 December 2019
Year(s) Of Engagement Activity 2019
URL https://www.iopconferences.org/iop/frontend/reg/thome.csp?pageID=854513&eventID=1370&traceRedir=2
 
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 Invited scientific talk at MRI Symposium (SGH 17 - Tourell) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact An invited scientific talk on our work during a half day Symposium organised by the University Hospital Southampton on MRI Research being conducted in Southampton.
Year(s) Of Engagement Activity 2017
 
Description Poster at International conference (GIDRM 18 - Melchiorre) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Poster on SAD-NMR at conference
Year(s) Of Engagement Activity 2018
 
Description Poster at major NMR conference (EUROMAR 18 - Tourell) 
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 the EUROMAR international meeting in Nantes, Fr. It generate good attention and questions by peers.
Year(s) Of Engagement Activity 2018
 
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