PhD in “Advancing Next-Generation Manufacturing: Harnessing Digital Twins and Process Analytical Technology (PAT) for Accelerated Chromatography Characterization”

Primary Supervisor:      Dr Stephen Goldrick (Department of Biochemical Engineering, UCL)  

Secondary Supervisor:  Prof Dan Bracewell (Department of Biochemical Engineering, UCL) 

Industrial Supervisor:    Dr James Savery (AstraZeneca, Cambridge) 

About the Project 

Project Aims: This project aims to develop a digital twin of chromatography operations, integrating seamlessly with all available online data from commercially available chromatography systems (e.g., ÄKTA systems). It will evaluate readily available Process Analytical Technology (PAT) for improved process control and streamlined process characterisation. The project will require a keen interest in modelling, experimental work, and 3-D printing. 

Benefits and Objectives: The digital twin of chromatography operations offers numerous benefits, including enhanced anomaly detection, tracking of resin performance drifts, integration with column lifecycle management, and efficient data management and storage. The primary objective is to construct a comprehensive and reliable model of the chromatography system, thereby reducing the experimental workload for process characterization. The incorporation of PAT enables real-time monitoring of key parameters such as titer and impurity levels, facilitating dynamic adjustments to chromatography loads to optimize process efficiency and minimize costs. To facilitate PAT integration, 3-D printing will be utilized within the project. 

Experimental Approach: The experimental approach will leverage platform knowledge, historical data, and Design of Experiments (DoE). The digital twin will serve as a mathematical representation of physiochemical transport and interactions.  The mechanistic modelling in chromatography will employ differential equations to depict molecule movement within and between resin beads and adsorption isotherms to quantify ligand competition during binding. This methodology enhances the understanding of existing processes by utilising historical data. The modelling allows for the simulation of elution profiles under various conditions, such as column dimensions, load ratio, flow rate, pH, temperature, and conductivity, for both major and minor sample components. Analysing these profiles generates potential pooling criteria that can be refined in silico before experimental validation. 

UCL-AstraZeneca CoE: This project will be part of the UCL-AstraZeneca Centre of Excellence (CoE) that is a joint collaboration between University College London (UCL) and AstraZeneca. The centre’s aim is to generate a set of predictive decisional tools for both upstream and downstream biopharmaceutical processing activities. This involves the application of micro-scale and high-throughput studies involving correlation development, multivariate data analysis (MVDA), process economics and discrete-event optimisation. The candidate will join a team of PhD and postdoctoral researchers working in the CoE across upstream and downstream processing as well as modelling tools. The project will be hosted by the department of Biochemical Engineering at University College London in collaboration with AstraZeneca sites across Cambridge (UK) and Gaithersburg (US).  

References:Armstrong, A., Horry, K., Cui, T., Hulley, M., Turner, R., Farid, S.S., Goldrick, S. and Bracewell, D.G., 2021. Advanced control strategies for bioprocess chromatography: Challenges and opportunities for intensified processes and next generation products. Journal of Chromatography A, 1639, p.461914. 

https://www.sciencedirect.com/science/article/pii/S0021967321000388 

Candidate requirements: 

Bachelor’s or Master’s degree in Biochemical Engineering / Chemical Engineering / Computer Science / Bioprocessing or relevant subject area 

Excellent written, verbal communication and presentation skills in English 

Interpersonal skills and ability to work effectively in a team 

Travel between UCL and AstraZeneca for experimental and research activities 

This project will require the candidate to possess basic engineering and computing skills and a desire to understand the challenges of dealing with complex biological materials in real environments.  

programming (Python, Matlab, R) or keen interest to learn 

3-D printing experience or interest 

Entry requirements 

A UK Master’s degree, or a minimum of an upper second-class UK Bachelor’s degree, in Biochemical Engineering,  Chemical Engineering or computer science  or relevant subject area with an interest in programming, modelling, 3-D printing, and hands-on experimental work or an overseas qualification of an equivalent standard). This project will require the candidate to possess engineering and computing skills and a desire to understand the challenges of dealing with complex biological materials in real environments. 

If your education has not been conducted in the English language, you will be expected to demonstrate evidence of an adequate level of English proficiency. The English language level for this programme is: Standard  

Informal enquiries should be addressed to Dr. Stephen Goldrick  (E-mail: s.goldrick@ucl.ac.uk) 

Deadline and Application Process 

The deadline for submission is 26th of August 2024

The interviews and timings will be confirmed with candidates. 

The successful candidate is expected to start 1st October 2024 

Please send a CV (max 2 pages) and covering letter outlining motivations for undertaking this studentship and relevant experience and expertise. Please send this directly to Dr. Stephen Goldrick (E-mail: s.goldrick@ucl.ac.uk) quoting ‘AstraZeneca PAT’ in the subject of the email.  

Candidates will be contacted via email for interview.  

In addition to this you must submit your formal application to the RRDBENSING01 Research Degree: Biochemical Engineering through UCL’s application portal by the above deadline of X. More information about the course and application process is available here: https://www.ucl.ac.uk/prospective-students/graduate/research-degrees/biochemical-engineering-mphil-phd#programme-choice  

Please note that the UCL application portal will be unavailable from 12pm Friday 9 August until 8am Thursday 15 August 2024, due to UCAS results embargo.