Dr Meghan Halse

Lecturer in Chemistry

01904 322853
Email: meghan.halse@york.ac.uk


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.

Hyperpolarised benchtop NMR spectroscopy

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.

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.

Ultra-low-field NMR and MRI

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. 

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.

NMR reaction monitoring with in situ photochemistry

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 

Time-resolved NMR spectroscopy with p-H2 hyperpolarisation


Current group members

Dr Peter Richardson (EPSRC-funded research associate, co-supervised with Simon Duckett)

Olga Semenova (PhD Student, co-supervised with Simon Duckett)

Ahmed Mohammed (PhD Student, co-supervised with Simon Duckett)

Alastair Robinson (MChem)


Dr Andrew Parrott (Pure and Applied Chemistry and CPACT, University of Strathclyde)

Former group members

Ben Tickner (MChem, co-supervised by Simon Duckett, 2016-17)

Scott Jackson (MChem, 2016-17)


Selected publications

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.2017, 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., 2015254, 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, 2015348, 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.2014136, 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., 201454, 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., 2013117, 5280-5290.

Quasi-equilibria in reduced Liouville spaces.
M E Halse, J-N Dumez and L Emsley, J. Chem. Phys., 2012136, 224511.

A common theory for phase-modulated homonuclear decoupling in solid-state NMR.
M E Halse, and L Emsley, Phys. Chem. Chem. Phys., 201214. 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., 201214, 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., 2009200, 88-94.

A dynamic nuclear polarisation strategy for multidimensional Earth's field NMR spectroscopy.
M E Halse and P T Callaghan, J. Magn. Reson., 2008195, 62-168.


Christmas Skating Party, December 2017

 The research group skating

(left to right) Ben Tickner, Will Duckworth, Olga Semenova, Jenny Lewis, Meghan Halse, Pete Richardson

 ‌The group at the christmas skating party

(left to right) Alastair Robinson, Ben Tickner, Meghan Halse, Olga Semenova, Jenny Lewis, Peter Richardson, Will Duckworth.