Ratiometric EPR-SRS probes for environmental sensing

About the Project

Optical microscopy has generated substantial impact for modern research. While fluorescence microscopy provides the ultimate sensitivity, it generally lacks chemical information. Complementarily, vibrational imaging provides rich chemical-bond-specific knowledge, however, frequently suffers from lower sensitivity. Recently, electronic preresonance stimulated Raman scattering (EPR-SRS) microscopy was described, achieving simultaneous high detection sensitivity and exceptional vibrational specificity of chromophores. This method readily breaks the optical colour barrier and is well suited for super-multiplex imaging in biological samples.

Within this project you will deliver a ratiometric EPR-SRS platform to report on pH and redox potential, two critical properties intimately entwined with cellular function. These first in class probes will provide a unique and ground-breaking method to establish the effect of exogenous signals, drug molecules and stress factors on the environment within organelles, define their relationship to basic biochemical processes and establish their effect on cellular health.

You will receive rigorous training in synthetic chemistry and become expert in the design, synthesis, isolation, purification and analysis of small organic molecules using multi-step syntheses. You will apply this skill set to the preparation of EPR probes suitable for Raman microscopy and use Stimulated Raman Microscopy to evaluate each compound prepared as an environmental sensor through cutting-edge spectroscopic methods. On development of suitable probes, you will learn cell culture techniques, examine your probes in a cellular environment and use them to establish the effect of exogenous signals on biochemical pathways. In addition, you will undertake a Postgraduate Certificate in Researcher Professional Development (PG Cert RPD) which has been designed to recognise the wide array of skills and experiences within their PhD training.

The ideal candidate will have a strong background and understanding of synthetic organic chemistry with a desire to apply these skills at the chemistry biology interface.

Funding Notes

48 month project with stipend at EPSRC rates and UK fees included.

References

Recent publications that have arisen through this collaboration:
Chem. Soc. Rev. 2025 in press. https://doi.org/10.1039/D5CS00748H
Angewandte Chem. 2023 e202311530.
Anal. Chem. 2023, 95, 5369–5376.
Anal. Chem. 2021, 93, 12786–12792.
Analyst, 2020, 145, 5289–5298.