High sensitivity pulse electron paramagnetic resonance spectroscopy for biomedical and biomolecular sciences

Electron paramagnetic resonance (EPR) spectroscopy detects the magnetism arising from the "spin", a quantum mechanical property, of unpaired electrons. In most molecules and materials electrons are paired, quenching their magnetism. However, in radicals and paramagnetic metal ions unpaired electrons persist and EPR is exclusively and exquisitely sensitive to these species. This can be exploited, e.g., in structural biology, where persistent radicals are linked to biomacromolecules, and their surroundings investigated, or distances between pairs of radicals can be measured on the nanometre scale. This approach has become a highly valuable complementary tool to explore the shapes and motion of biomacromolecules and their complexes as they function. Combined with recent advances in deep-learning, this has become a powerful tool to predict and validate structure-function relationships of biological systems. Investing in technology that can experimentally validate computational structures with very modest sample requirements will be strategically important for the UK.

St Andrews has a strong track record in biological pulse EPR methodology. The current workhorse pulse EPR equipment is based on a 20-year-old instrument that has had repeated downtime due to critical repairs. While this existing Q-band equipment housed in Physics is of world-leading sensitivity, expanding capacity and enabling higher throughput that will facilitate new research are a clear priority for the University and aligned with the strategic objectives of the BBSRC.

To achieve this capability, we propose to upgrade the pulse EPR spectrometer installed in 2011 in the School of Chemistry and embedded in the Biomedical Sciences Research Complex (BSRC) from X-band to Q-band giving a twenty-fold sensitivity improvement over its current capability. Addition of a small sample access probe head will increase absolute sensitivity, compared to the existing Q-band, by four-fold. This will provide a significant boost to research, facilitating high quality data for samples available in only limited quantities, provide critical contingency in the case of instrument outage for maintenance or repairs, while simultaneously extending capacity that will allow higher throughput and widen access to other users. Of specific interest, recent developments in EPR technology allow measuring distances between fluorine atoms and spin-labels for structural restraints or the use of laser excitation for light-induced spin centres. Both innovations have generated significant interest in the EPR community and are starting to become more widely applied. However, in St Andrews the requirement of additional downtime for reconfiguration and testing means that only the expanded capacity of the upgraded instrument would allow exploring these new opportunities more widely.

With this proposal, we therefore seek:

(i) Funds to support procurement and installation of a Q-band upgrade to the pulse EPR spectrometer in the BSRC and

(ii) To use this upgraded facility to provide training of existing and new users, and exploration of new frontier bioscience research opportunities.

The upgrade will enable research that spans four academic schools in St Andrews and a wide network of local, national, and international collaborations including bioscience for health, exploring fundamental biological mechanisms, novel imaging materials, chemical biology, and sustainable feedstocks.