Application of low-field NMR/MRI in biopharmaceutical development

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.