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

该项目旨在开发创新的非侵入性磁共振(MR)微成像方案和本地化磁共振波谱方法，以直接探测柱内发生的色谱分离过程中蛋白质/柱的相互作用。快速T1和T2弛豫测量方法和局部1H核磁共振波谱将用于研究蛋白质捕获/洗脱，而扩散加权核磁共振和核磁共振测速将用于研究传质现象。这一方法与BBSRCS工业研究优先领域2相协调，旨在提供一个严谨的、具有科学动机的平台，以简化和提高生物过程工程的效率，从而在英国生物经济中创造新的投资和机会。该项目直接涉及BBSRC的工业生物技术和生物能源优先领域，旨在评估磁共振成像和光谱分析作为一种新工具的使用，以帮助开发层析纯化过程，并加深对蛋白质分离中一些挑战背后的理解。虽然各种基于亲和和非亲和的层析方法在生物制药生产中得到了很好的建立，并且通常可以很好地进行控制，但在层析过程中固定基质和蛋白质产品之间发生的物理化学相互作用的确切机制并不总是被完全理解。了解这些相互作用，以及工艺参数对蛋白质/基质相互作用的影响，对于具有挑战性的分子尤其重要。在这项工作中，核磁共振将被作为一种工具进行评估，以帮助理解蛋白质在层析过程中异常行为的根本原因，这将对生物过程的开发具有重要价值。

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.