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Revolutionising cell therapy manufacture via development of microfluidic media exchange systems

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  • Full or part time
    Dr H Bridle
    Dr Nik Willoughby
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

This project is one of 16 four year PhD Studentships funded by Medical Research Scotland (https://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and External Partner Organisation (EPO). The Studentship will provide the first-class academic and additional training provided by the EPO needed to equip the successful candidate for a science career in an increasingly competitive market.

"Revolutionising cell therapy manufacture via development of microfluidic media exchange systemsn" to be delivered by Heriot-Watt University [Supervisors: Dr Helen Bridle and Professor Nik Willoughby (both Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences)] and Scottish National Blood Transfusion Service (SNBTS) (scotblood.co.uk) [EPO: Dr Alasdair Fraser].

Cellular therapies are a fast-growing, highly innovative and effective area of medicine, which encompasses well-characterised immune therapies for infection and cancer, as well as ground-breaking approaches aimed at regenerating diseased tissue. The cell therapy market is huge and rapidly expanding: an estimate of worldwide annual revenue in 2016 was $8.8 billion, representing 20% growth on the previous year. Over 1000 products are already in the clinical pipeline.

The key issue for manufacturing defined, effective cellular therapies is to establish robust manufacturing and analysis processes which ensure a product which meets all Critical Quality Attributes. Large-scale centrifugation to process cultured cells remains a persistent and significant problem in manufacture of cellular therapeutics, as it can lead to significant reductions in yield (up to 50% in CD34+ haematopoietic stem cells) and cell damage (changes in gene expression and differentiation pathways), particularly in post-thaw cryopreserved products. Currently there are few non-centrifugation based options for volume reduction or buffer exchange. Buffer exchange is essential as culture medium is unacceptable as a final formulation excipient due to the presence of exogenous growth factors and metabolites.

We propose a scalable microfluidic solution switching approach to allow rapid and controlled exchange of media and buffers during cell therapy manufacture. This offers potentially significant improvements in cell yield and function for cell-based treatments. In addition, this technology could be applied to removal of cryopreservatives from thawed haematopoietic stem cell transplants. Examples of diseases areas for which this technology would be particularly useful for treatments currently manufactured by SNBTS include the generation of macrophages from monocyte precursors for the treatment of chronic liver disease and the isolation of Epstein-Barr virus specific cytotoxic T cells for treatment of post-transplant lymphoproliferative disease (PTLD). Improved processes for generating, culturing and harvesting these cells is a strategic priority for SNBTS. The project is based on an inertial focussing microfluidic prototype device, which has demonstrated proof-of-principle. The focus of the PhD is to redesign the system for optimal function, validate performance across a range of therapies and work towards GMP manufacturing and scale-up devices.

ENQUIRIES:
Enquiries should be sent by email to Dr Helen Bridle:
[Email Address Removed]

APPLICATIONS:
Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK, in a relevant subject area. Applications are welcomed from both engineers and biologists - training will be provided as required.

Applications must be submitted online by following the instructions at, and the "APPLY NOW" link at
https://www.hw.ac.uk/study/apply/uk/postgraduate.htm
Please select the Bioengineering and Biosciences subject area when competing your appliciton.

When submitting your online application, please also submit a CV; the contact details of 2 references (including email addresses); copies of your degree transcripts; and a covering letter, explaining why the applicant wishes to carry out this project.

Please note, your application may be shared with the funders of this PhD Studentship, Medical Research Scotland and Scottish National Blood Transfusion Service (SNBTS).

Interviews are expected to take place 3-4 weeks after the closing date for applications. In light of the current coronavirus situation, interviews may be conducted by video conference.

It is anticipated that the PhD Studentship will start in October 2020.

Funding Notes

PhD Studentship provides: an annual tax-free stipend of £17,500, increasing to £18,000 over the four years; tuition fees at UK/EU rates only; consumables; and generous travel allowance. International fees are not covered.

How good is research at Heriot-Watt University in General Engineering?
(joint submission with University of Edinburgh)

FTE Category A staff submitted: 108.84

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities


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