Use of magnetic resonance imaging and spectrometry to address challenges in chromatographic separations of biopharmaceuticals

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The project aims to develop innovative non-invasive magnetic resonance (MR) micro imaging protocols and localised MR spectroscopy methods to directly probe protein/column interactions during chromatographic separation processes occurring within the column. Fast T1 & T2 relaxometry methods and localised 1H NMR spectroscopy will be used to study protein capture/elution whilst diffusion weighted MRI and MRI velocimetry will be used to study mass transfer phenomena. This approach is harmonised with the BBSRCs industrial research priority 2 area and aims to provide a rigorous, scientifically motivated, platform to streamline and improve the efficiency of bioprocess engineering and thus creating new investments and opportunities in the UK bio-economy. The project directly addresses the BBSRC' priority area of Industrial Biotechnology and Bioenergy and is designed to evaluate the use of magnetic resonance imaging and spectrometry as a new tool to aid development of chromatographic purification processes and deepen the understanding behind some of the challenges in protein separations. Whilst various affinity and non-affinity based chromatographic methods are well established in biopharmaceutical production and can typically be well controlled, the exact mechanisms of the physicochemical interactions that occur between the stationary matrix and protein product during chromatography is not always fully understood. Understanding those interactions, and the impact of process parameters on protein/matrix interactions, is especially significant for challenging molecules. In this work NMR will be evaluated as a tool to help understand the underlying cause for atypical behaviour of proteins during chromatography and this would be of significant value for development of bioprocesses.