Lecturer in Chemistry
SABRE hyperpolarised 13C benchtop NMR Spectroscopy
My research interests centre on the development of new nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) methods with a particular focus on the use of hyperpolarisation and low-cost, portable instrumentation to open up new applications.
Magnetic resonance (MR) is an invaluable tool for applications ranging from chemical analysis to clinical diagnosis. The power of MR lies in the wealth of molecular-level information available and the selectivity and control provided by the use of radio-frequency irradiation and magnetic field gradients to tune the evolution of the MR signals. In magnetic resonance, the signal arises from the difference in population between nuclear spin states in the presence of an external magnetic field. This population difference is so small that only 33 in every million nuclear spins contribute to the observed signal in a standard experiment in a magnetic field of 9.4 T. The quest for higher sensitivity has led to an increase in the strength of the magnetic fields in NMR and MRI devices over the past several decades, making NMR and MRI very expensive. There are many applications where it would be preferable to be able to use a lower-cost and more portable instrument. In order for this to be possible, we need to find clever ways of overcoming the low sensitivity problem of NMR and MRI.
Hyperpolarisation is a general term used to describe the generation of nuclear spin population differences that are orders of magnitude larger than the thermal distribution dictated by Boltzmann statistics (ie what we get under normal circumstances). This increase in polarisation leads directly to an increase in the observed NMR or MRI signal. These methods require a source of spin order that can be transferred to the target nuclear spins. One method that has shown a lot of potential in recent years is parahydrogen induced polarisation (PHIP). Parahydrogen (p-H2) is the thermally preferred (lowest energy_ nuclear spin isomer of molecular hydrogen. It exists in a pure nuclear singlet state, which has no net magnetic moment and so provides no NMR or MRI signal. However, when the symmetry of the environments of the two 1H nuclei in p-H2 is broken, through a chemical reaction such as oxidative addition at a metal centre or hydrogenation of an unsaturated substrate, this pure singlet state evolves into observable magnetisation. Due to the purity of the initial state, the resultant NMR signals are amplified by factors of up to tens of thousands.
Researchers at York, led by Professor Simon Duckett, have recently developed a new approach to parahydrogen hyperpolarisation called signal amplification by reversible exchange (SABRE). In SABRE the spin order from p-H2 is transferred catalytically, without the need to chemically change the target molecule. The transfer of polarisation is mediated by a transition metal catalyst that reversibly binds p-H2 and one or more molecules of the target molecule, establishing a coupling network that promotes the transfer of spin order from one to the other. Subsequent chemical exchange of the hyperpolarised bound molecule gives rise to a reservoir of hyperpolarised free molecules in solution. This transformative technique has led to the establishment of the Centre for Hyperpolarisation in Magnetic Resonance (CHyM) at the University of York.
The SABRE hyperpolarisation approach is attractive for use with low-cost and portable benchtop NMR spectrometers because the polarisation, and hence NMR signal enhancements, generated by SABRE is independent of the strength of the magnetic field inside the NMR spectrometer that is used to observe the signal response. Therefore signal increases by factors of >10,000 can be observed even in weak detection fields. One of the main research areas in my group involves the integration of SABRE hyperpolarisation with benchtop NMR spectrometers, which typically have magnetic fields of 1- 2 T, with a view to developing and optimising this technique for applications in industry and/or human health. This work is funded by the Engineering and Physical Sciences Research Council (EPSRC) and is a collaboration with Professor Simon Duckett at York and Dr Alison Nordon at the University of Strathclyde in Glasgow.
Signal amplification by reversible exchange (SABRE), a catalytic method for generating NMR hyperpolarisation, enables high-sensitivity benchtop (1 T) NMR spectroscopy of low-concentration analytes, even in non-deuterated solvents.
At the heart of the catalytic SABRE process is a transfer of polarisation from p-H2 to the target molecule in a magnetic field that is more than 1000 times weaker than a typical NMR magnet. This magnetic field range is often referred to as the zero-to-ultra-low-field (ZULF) regime. In this project, we are interested in directly observing the generation of SABRE hyperpolarisation in situ (ie under the same experimental conditions as it is generated) in order to better understand and thus optimise this process. In addition, NMR detection in the ZULF regime opens the door to truly low-cost and portable NMR and MRI solutions in the future. This work is funded by the Engineering and Physical Sciences Research Council (EPSRC) through a New Investigator Award.
Hyperpolarisation allows 1H NMR and MRI to be performed on very small volumes of analyte in the Earth’s field (~50 µT), which is 200,000 times weaker than a standard NMR magnet.
Another research area in my group involves the development of a time-resolved NMR spectroscopy method using laser initiation and NMR detection with p-H2 hyperpolarisation. In contrast to conventional p-H2-enhanced experiments, where the chemical reaction involving p-H2 occurs asynchronously (randomly) and the reaction time is long (seconds) on the timescale of the coherent evolution of the NMR signals (µs – ms), here we initiate the reaction with p-H2 photochemically using a 10 ns laser pulse. This coherent initiation step allows us to observe the build-up of parahydrogen hyperpolarisation on a microsecond timescale. The goal of this work is to develop a robust time-resolved NMR tool for measuring reactivity on micro-to-millisecond timescales. This project is a collaboration with Professor Simon Duckett and Professor Robin Perutz.
Time-resolved NMR spectroscopy with p-H2 hyperpolarisation
Meghan joined the York Chemistry department in 2013 following periods of work and study at the University of New Brunswick in Canada, Victoria University of Wellington in New Zealand and the CNRS in Lyon, France. Meghan is a physical chemist and NMR spectroscopist who is interested in developing new NMR and MRI instruments and methods. Meghan’s research group focuses in particular on the development of portable, low-field NMR and MRI devices that can be used for applications outside of the traditional laboratory environment. Current research projects use parahydrogen-based hyperpolarisation methods to increase the sensitivity of low-field NMR in order to enable new applications. In addition to her research, Meghan teaches the fundamentals of magnetic resonance and a range of maths and physical chemistry topics at an undergraduate level.
Olga is a 4th year PhD student working under the joint supervision of Meghan Halse and Simon Duckett. Olga’s research concerns the development of low-field NMR instrumentation for industrial use. In particular she aims to develop reaction monitoring methods using a benchtop (1 T) NMR spectrometer. To achieve this, the cutting-edge SABRE (signal amplification by reversible exchange) technique is applied in order to increase the sensitivity of the benchtop spectrometer. SABRE uses iridium complexes to catalytically transfer polarisation from parahydrogen to a target molecule. Olga is using the lifetime of SABRE-enhanced NMR signals as a probe of chemical change. She has applied this to monitor the activation of the SABRE catalyst and the chemical transformation of the target molecule, which undergoes hydrogen isotope exchange. In the future, the aim is to broaden the range of reactions that can be monitored so that this technology can be used in industry by specialists and non-specialists to monitor reactivity using benchtop NMR.
Peter joined the group in 2015 as a PDRA working on a collaborative project led by Simon Duckett and Meghan Halse in York and Alison Nordon at the University of Strathclyde in Glasgow. Peter’s research interests lie in the synthesis and characterisation of materials and instrumentation development. His current research is focused on the development of a low field (1T) NMR instrument to be used for process monitoring, control and optimisation, with the aim of achieving the sensitivity and specificity of a high field spectrometer via the use of parahydrogen hyperpolarisation. Other research includes the development of a bespoke polarisation delivery system based on the already existing flow system developed at ChyM with industrial partners for in situ hydrogenation of samples. Alongside the NMR instrumentation development research, industrial and academic applications for the low cost low field spectrometer are being explored utilising both the parahydrogen induced polarisation (PHIP) and signal amplification by reversible exchange (SABRE) methods of hyperpolarisation.
Ahmed is a 2nd year PhD student working under the joint supervision of Meghan Halse and Simon Duckett. The initial object of Ahmed’s research is to establish methods to measure T1 values of hyperpolarized samples in the Earth’s magnetic field (EFNMR) using the SABRE technique. This is required to optimize the SABRE hyperpolarization method, for use in the EFNMR and more generally. This method will then be used to explore the effects of different catalysts, substrates and experimental conditions on SABRE hyperpolarisation lifetimes.
Fraser is a post-doctoral researcher working on an EPSRC-funded project under the supervision of Meghan Halse. Fraser’s research interests broadly lie in the development of new Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) techniques and hardware. His focus is on using novel hyperpolarisation methods and low cost, low magnetic field instruments to expand typically prohibitively expensive techniques to new applications. To facilitate these goals, his current research involves the design and fabrication of novel low cost scientific instruments including parahydrogen generators, automated polarisation transfer systems and low magnetic field NMR detectors. These systems will be used to explore polarisation transfer mechanisms of both Para-Hydrogen Induced Polarisation (PHIP) and Signal Amplification by Reversible Exchange (SABRE) methods of hyperpolarisation. Outside fundamental research, Fraser is interested in developing new industrial applications of low cost NMR and MRI techniques.
Fraser’s previous research has included the use of bespoke low cost Magnetic Resonance (MR) relaxometry sensors for environmental monitoring in the EU Seventh Framework program project - ARBI (Automated Reed Bed Instillations). Additionally Fraser has performed significant research into other MR hyperpolarisation techniques, particularly Spin Exchange Optical Pumping (SEOP) of noble gasses for Gas phase NMR and MRI. With applications ranging from non-invasive characterization of dynamics in complex porous media, chemical biosensors and pulmonary imaging.
Alastair is a PhD student who is jointly supervised by Meghan Halse and Simon Duckett. Alastair started his PhD in 2018 and has previously worked in the group as a summer student in 2016 and as an MChem student in 2017-18. His PhD research is focused on the incorporation and optimisation of photochemical methods on a benchtop NMR spectrometer. By initiating reactions within the spectrometer, he hopes to perform time-resolved NMR experiments to investigate parahydrogen-based hyperpolarisation mechanisms in a range of transition metal complexes. To aid in this project, he will develop several novel NMR pulse sequences and simulations as to allow for the effective analysis of the chemical systems involved.
Matheus is a PhD student working under the supervision of Meghan Halse. Matheus joined the group in 2018 after completing an MChem at the University of Southampton. For his PhD project, Matheus is working on in situ NMR detection in low magnetic fields of parahydrogen derived hyperpolarisation. The project focused in particular on the build-up of 1H hyperpolarisation and the transfer to other nuclei in the uT – mT regime through the use of simulation and experiment.
Kieran is a 4th year MChem student. He is currently doing a research project under the supervision of Meghan Halse on Earth’s field NMR with in situ parahydrogen hyperpolarisation. Kieran’s project focuses on the design and implementation of new hyperpolarised experiments using Earth’s field NMR detection.
Aminata is a PhD student, jointly supervised by Simon Duckett and Meghan Halse. Aminata is working in York as part of the European Zero and Ultra-Low Fields (ZULF) NMR Innovative Training Network. Aminata completed her BSc (2012) and MSc (2014) at University Joseph Fourier in Grenoble France. Her studies included internships at the EPFL in Lausanne, Switzerland and at the CNRS in Grenoble, France. Aminata joined the group in York in 2018. Her PhD involves using the signal amplification by reversible exchange (SABRE) hyperpolarisation method with zero and ultra-low field NMR detection.
Quantification of hyperpolarisation efficiency in SABRE and SABRE-Relay enhanced NMR spectroscopy
P. M. Richardson, R. O. John, A. J. Parrott, P. J. Rayner, W. Iali, A. Nordon, M. E. Halse, and S. B. Duckett, Physical Chemistry Chemical Physics, 2018, 20, 26362-26371. DOI: 10.1039/C8CP05473H
Quantitative In-situ Monitoring of Parahydrogen Fraction Using Raman Spectroscopy
A. J. Parrott, P. Dallin, J. Andrews, P. M. Richardson, O. Semenova, M. E. Halse, S. B. Duckett, and A. Nordon, Applied Spectroscopy, 2018 (in press) DOI: 10.1177/0003702818798644
SABRE hyperpolarisation enables high-sensitivity 1H and 13C benchtop NMR spectroscopy
P. M. Richardson, A. J Parrott, O. Semenova, A. Nordon, S. B. Duckett, M. E. Halse, Analyst, 2018, 143, 3442-3450. DOI: 10.1039/C8AN00596F
A simple hand-held magnet array for efficient and reproducible SABRE hyperpolarisation using manual sample shaking
P. M. Richardson, S. Jackson, A. J Parrott, A. Nordon, S. B. Duckett, M. E. Halse, Magn. Reson. Chem., 2018, 56, 641-650. DOI: 10.1002/mrc.4687
Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation
M. E. Halse, B. Procacci, S. L Henshaw, R. N. Perutz, S. B. Duckett, J. Magn. Reson., 2017, 278, 25-38. DOI: 10.1016/j.jmr.2017.03.005
Photochemical pump and NMR probe to monitor the formation and kinetics of hyperpolarized metal dihydrides.
B. Procacci, P. M. Aguiar, M. E. Halse, R. N. Perutz, S. B. Duckett, Chem. Sci., 2016, 7, 7087-7093. DOI: 10.1039/C6SC01956K
Macroscopic Nuclear Spin Diffusion Constants of Rotating Polycrystalline Solids from First-Principles Simulation
M E Halse, A Zagdoun, J-N Dumez and L Emsley, J. Magn. Reson., 2015, 254, 48-55. DOI: 10.1016/j.jmr.2015.02.016
Direct observation of hierarchical protein dynamics.
J R Lewandowski, M E Halse, M Blackledge and L Emsley, Science, 2015, 348, 578-58. DOI: 10.1126/science.aaa6111
Photochemical pump and NMR probe: Chemically created NMR coherence on a microsecond time scale.
O Torres, B Procacci, M E Halse, R W Adams, D Blazina, S B Duckett, B Eguillor, R A Green, R N Perutz and D C Williamson, J. Am. Chem. Soc., 2014, 136, 10124- 0131. DOI: 10.1021/ja504732u
High-resolution 1H solid-state NMR spectroscopy using windowed LG4 homonuclear dipolar decoupling.
M E Halse, J Schlagnitweit and L Emsley, Isr. J. Chem., 2014, 54, 134-146.
Improved phase-modulated homonuclear dipolar decoupling for solid-state NMR spectroscopy from symmetry considerations.
M E Halse and L Emsley, J. Phys.Chem. A., 2013, 117, 5280-5290.
Quasi-equilibria in reduced Liouville spaces.
M E Halse, J-N Dumez and L Emsley, J. Chem. Phys., 2012, 136, 224511.
A common theory for phase-modulated homonuclear decoupling in solid-state NMR.
M E Halse, and L Emsley, Phys. Chem. Chem. Phys., 2012, 14. 9121-9130.
A first-principles description of proton-driven spin diffusion.
J-N Dumez, M E Halse, M Butler and L Emsley, Phys. Chem. Chem. Phys., 2012, 14, 86-89.
Quantitative analysis of Earth's field NMR spectra of tightly coupled heteronuclei.Quantitative analysis of Earth's field NMR spectra of tightly coupled heteronuclei.
M E Halse, P T Callaghan, B Feland and R E Wasylishen, J Magn. Reson., 2009, 200, 88-94.
A dynamic nuclear polarisation strategy for multidimensional Earth's field NMR spectroscopy.
M E Halse and P T Callaghan, J. Magn. Reson., 2008, 195, 62-168.
Robin started his PhD under the joint supervision of Meghan Halse and Simon Duckett in October 2015. He was unable to complete his studies due to ill health and sadly passed away in December 2017. His good humour and endless supply of trivia knowledge are very much missed in the group.
Ben did a 4th year MChem project in 2016-2017 that was co-supervised by Meghan Halse and Simon Duckett. He is now working towards a PhD under the supervision of Simon Duckett in the Centre for Hyperpolarisation in Magnetic Resonance (CHyM).
Scott did a 4th year project in the group in 2016-2017. Scott is now working towards his PhD in the group of Victor Chechik.
Christmas Skating Party, December 2017
(left to right) Ben Tickner, Will Duckworth, Olga Semenova, Jenny Lewis, Meghan Halse, Pete Richardson
(left to right) Alastair Robinson, Ben Tickner, Meghan Halse, Olga Semenova, Jenny Lewis, Peter Richardson, Will Duckworth.