Application of low-field NMR/MRI in biopharmaceutical development

生物制药开发的一个关键目标是降低成本并加快细胞培养过程的开发。为此，改进的载体构建和过程开发需要与改进的分析相结合。阿斯利康是一家全球、以科学为主导的生物制药公司，为全球数百万患者提供创新药物，该公司提供为期4年的博士生学习机会；成功的申请者应预期每年至少在阿斯利康的实验室工作一个月。我们与领先机构的科学家合作，更好地了解疾病，识别潜在的新药，并加快药物开发。这个博士项目是与我们的生物制药开发团队合作的-在盖瑟斯堡(美国)、旧金山(美国)、剑桥(英国)和利物浦(英国)设有设施-提供从早期研究到后期开发的项目。细胞培养发酵科学组是BPD的职能部门之一，使用高通量缩小模型来生成抗体生产的最佳细胞系和工艺，并负责将技术转移到生产中。核磁共振(核磁共振)是一种非侵入性分析技术，有可能通过使用低成本、低场强、便携式台式核磁共振光谱仪开发用于生产线或在生产线上使用。我们的团队最近表明，使用基于扩散的核磁共振技术可以区分细胞内和细胞外的蛋白质1。该博士学位的主要目标是为低场、台式核磁共振系统开发核磁共振扩散和T1/T2弛豫测量技术，最终提供一种可在生物制药生产线上使用的非侵入性核磁共振工具，以监控关键的细胞生长和生产率参数。此外，本项目将使用磁共振成像(MRI)测速仪来研究灌流生物反应器滞留过滤器内的流场和剪切场，以便更定量地了解此类过程中的传质过程。位于化学工程和生物技术系的磁共振研究中心(MRRC)是一家世界级的设施，在将磁共振技术应用于化学和生化工程领域的学术和工业研究方面拥有广泛的专业知识。该小组由来自化学工程、物理、化学和生物等广泛背景的研究人员组成；这不仅反映了我们对磁共振技术应用的兴趣，也反映了我们对开发新的实验和数据分析技术的兴趣，这些技术使我们能够将磁共振应用于越来越多的研究问题。

A key goal in biopharmaceutical development is to reduce costs and accelerate cell culture process development. To do this improved vector construction and process development needs to be coupled with improved analytics.A 4 year Ph.D. studentship is available with AstraZeneca, a global, science-led biopharmaceutical company delivering innovative medicines to millions of patients worldwide; the successful applicant should expect to spend at least one month per year in AstraZenca's labs. We work alongside scientists at leading institutions to better understand disease, identify potential new drugs and accelerate drug development. This Ph.D. project is a collaboration with our BioPharmaceutical Development team - with facilities in Gaithersburg (US), San Francisco (US), Cambridge (UK) and Liverpool (UK) - which delivers projects from early research to late stage development. The Cell Culture Fermentation Sciences group, one of the functional areas within BPD, uses high throughput scale-down models to generate optimal cell lines and processes for antibody production and is responsible for technology transfers into manufacturing.Nuclear Magnetic Resonance (NMR) is a non-invasive analytical technique which has the potential to be developed for use in or at the production line with the use of low-cost, low-field, portable benchtop NMR spectrometers. Our group has recently shown it is possible to distinguish between intra and extracellular proteins using diffusion based NMR techniques1. The overarching aim of this Ph.D. is to develop NMR diffusion and T1/T2 relaxometry techniques for low-field, benchtop NMR systems ultimately providing a non-invasive NMR tool that can be used in/at the biopharmaceutical production line to monitor critical cell growth and productivity parameters. In addition this project will use magnetic resonance imaging (MRI) velocimetry to study the flow and shear fields inside the retention filters of a perfusion bioreactor in order to gain a more quantitative understand of mass transfer during such processes. The magnetic resonance research centre (MRRC) based in the Department of Chemical Engineering and Biotechnology is a world class facility with wide ranging expertise in the application of magnetic resonance techniques to academic and industrial research in the field of chemical, and biochemical engineering. The group consists of researchers from a wide range of backgrounds, including chemical engineering, physics, chemistry and biology; this reflects our interest not only in the applications of magnetic resonance techniques, but also the development of new experimental and data analysis techniques that enable us to apply magnetic resonance to an ever-increasing range of research problems.