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和加速细胞培养工艺的开发。要做到这一点，改进的载体建设和工艺开发需要与改进的分析相结合。AstraZeneca是一家全球性的、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;成功的申请人每年至少要在AstraZeneca的实验室工作一个月。我们与领先机构的科学家合作，以更好地了解疾病，识别潜在的新药并加速药物开发。这个博士该项目是与我们的生物制药开发团队的合作-在盖瑟斯堡（美国），旧金山弗朗西斯科（美国），剑桥（英国）和利物浦（英国）的设施-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的功能领域之一，使用高通量缩小模型生成最佳细胞系和抗体生产工艺，并负责将技术转移到生产中。核磁共振（NMR）是一种非侵入性分析技术，具有开发用于生产线的潜力，可使用低成本，低场，便携式台式NMR光谱仪。我们的团队最近表明，使用基于扩散的NMR技术可以区分细胞内和细胞外蛋白质1。这个博士学位的首要目标。是为低场台式NMR系统开发NMR扩散和T1/T2弛豫技术，最终提供一种非侵入性NMR工具，可用于生物制药生产线，以监测关键的细胞生长和生产率参数。此外，该项目将使用磁共振成像（MRI）测速技术来研究灌注生物反应器的截留过滤器内的流场和剪切场，以便更定量地了解这些过程中的传质。位于化学工程和生物技术系的磁共振研究中心（MRRC）是一个世界级的设施，在磁共振技术应用于化学和生物化学工程领域的学术和工业研究方面具有广泛的专业知识。该小组由来自广泛背景的研究人员组成，包括化学工程，物理学，化学和生物学;这反映了我们不仅对磁共振技术的应用感兴趣，而且还对新的实验和数据分析技术的发展感兴趣，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.