In almost all engineering sectors there has been a successful transition from batch to continuous processing. One particularly promising area for continuous processing in biochemical engineering is the biocatalytic synthesis of active pharmaceutical ingredients (APIs) and value-added chemicals. However, continuous production at large scale has not yet been successfully demonstrated. Continuous-flow biocatalysis offers an improved control over reaction conditions with benefits in yield and productivity levels. This increase in efficiency and concomitantly minimization of waste will ultimately result in cleaner processes with lower overall costs. Furthermore, continuous processes enable a reduction in process lines and facility footprints which in turn result in less up-front capital investment. To exploit the full benefits of continuous processing, it is necessary to characterise reactor performance, and to understand the interplay between the biocatalysts’ constraints and the reactor operation. Only then can these processes be exploited to successfully at industrially relevant volumes.
To achieve this aim, scale-down models that enable careful assessment of reactor performance and biocatalysts’ behaviour are necessary. Miniaturized continuous-flow reactors are prime candidates. Their small dimensions allow experiments to be performed with much smaller volumes compared to traditional batch systems, offering significant cost reduction when using expensive substrates or enzymes. Within these reactors the control of reaction parameters is facilitated, and in-line purification with recovery of products has been demonstrated. Additionally, reactions can be potentially accelerated due to enhanced mass transfer with a concomitant decrease in reaction time. Therefore, miniaturized continuous-flow reactors will in the future form the basis to acquire high-quality data rapidly and with high throughput.
• Design, fabricate, and characterize a miniaturized continuous-flow reactor with integrated optical sensors and at-line analytical tools for the on-line monitoring of chemical and physical variables (pH, temperature, oxygen and CO2) and for at line reaction analytics (GC- and LC-MS).
• Validate the integrated miniaturized continuous-flow reactor with industrially relevant biocatalytic reactions.
• Compare the reactor performance in batch and continuous systems (e.g. by space-time yields, (gproduct/(Lreactor.h), and (gproduct/genzyme)) at all scales assessing process stability, quality profile of the products and scalability.
Output & Impact
This project aligns with UK strategic priorities in the area of Industrial Biotechnology and the recently funded EPSRC Future Biomanufacturing Research Hub of which the department is a key spoke. Due to the high relevance and timeliness of this research direction, we anticipate that each objective of the project will lead to a publication output. The results obtained throughout this project will be included in teaching of undergraduates or postgraduate modules.
Applicants should have a degree equivalent to a UK first class honours, or a high upper second class, in Engineering or Physical Sciences. This PhD will be multidisciplinary, straddling both biochemical and chemical engineering. The successful candidate should have strong analytical skills and aptitude for biocatalysis, reactor engineering and numerical modelling.
The starting date for this PhD will be January 2020. To apply for this studentship, please send your two-page CV and cover letter by email to Ms Andrea Kezer, CDT Manager & Postgraduate Programmes Manager ([email protected]
) to arrive no later than 12pm on Thursday, 12th December 2019. For queries related to this position, please contact Dr Marco Marques (Supervisor: [email protected]
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.