Dr Meghan Halse
Senior Lecturer in Chemistry
01904 322853
Email: meghan.halse@york.ac.uk
Research
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.
Nuclear magnetic resonance (NMR) is an invaluable tool for applications ranging from chemical analysis to clinical diagnosis. The power of NMR lies in the wealth of molecular-level information available but it is limited by low sensitivity. This can be overcome by using strong magnetic fields, but high-field NMR instruments are large and expensive. There are many applications where it would be preferable to be able to use a lower-cost and more portable instrument but this is only feasible if the issue of low sensitivity can be overcome.
Hyperpolarisation methods increase the sensitivity of NMR by generating nuclear spin population differences that are orders of magnitude larger than what we get under normal circumstances. This leads directly to an increase in the observed NMR signal strength. In our work, we focus primarily on parahydrogen induced polarisation (PHIP). Parahydrogen (p-H2) is a special form of hydrogen gas that exists in a so-called pure nuclear singlet state. In itself p-H2 provides no NMR signal, but when it is involved in a chemical reaction p-H2 can generate NMR signals that are amplified by factors of up to tens of thousands. This effect does not depend on a strong magnetic field and so can be combined with low-field and low-cost detectors.
Researchers at York, led by Prof Simon Duckett, have recently developed a new approach to parahydrogen hyperpolarisation called signal amplification by reversible exchange (SABRE). SABRE is completely reversible so it can be applied multiple times to the same sample without changing the chemical identity of the target molecule. 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
Signal amplification by reversible exchange (SABRE), a catalytic method for generating NMR hyperpolarisation, enables high-sensitivity benchtop (1 T) 13C and 1H NMR spectroscopy.
The SABRE hyperpolarisation approach is attractive for use with low-cost and portable benchtop NMR spectrometers because the NMR signal enhancements that generated by SABRE are independent of the strength of the magnetic field inside the NMR spectrometer that is used for detection. 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 University of York and Dr Alison Nordon at the University of Strathclyde in Glasgow.
SABRE-enhanced benchtop NMR can be used for analytical applications such as reaction monitoring.
Ultra-low-field NMR and MRI
At the heart of the SABRE process is a transfer of NMR signal 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 (i.e. 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 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. More recently, we have begun to expand this work for detection using a benchtop NMR spectrometer.
This project is a collaboration with Professor Simon Duckett and Professor Robin Perutz.
Time-resolved NMR spectroscopy with p-H2 hyperpolarisation
