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Readying Miniaturized Reactors for Flow Biocatalysis


Department of Biochemical Engineering

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Dr M Marques No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

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.

Project Objectives
• 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 process and scalability.

Output & Impact
This project aligns with UK strategic priorities in the area of Industrial Biotechnology and the departmental EPSRC Future Biomanufacturing Research Hub. 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.



Applications
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 28 September 2020. To apply for this studentship, please send your max. two-page CV and cover letter by email to Dr Marco Marques, project supervisor to arrive no later than 12pm on Monday, 13th July 2020. In addition to this, you must submit your formal application through UCL’s Application portal for the Research Degree: Biochemical Engineering course for 20/21 entry. More information about the application process is available on the department’s website: https://www.ucl.ac.uk/biochemical-engineering/study/postgraduate-research/biochemical-engineering-mphilphd

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

Funding Notes

This research project has funding attached. It is only available to UK citizens or EU citizens. The studentship covers the full cost of UK/EU tuition fees, plus a tax free stipend for four years. Annual stipend for 20/21: £17,285.
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