Student Profile

William Bowen

William Bowen

Downstream processing challenges for bringing human therapeutic cells to the clinic

PhD Supervisor(s): E Theodosiou, K Coopman, C Hewitt, and P Levison

Loughborough Univerrsity

Contact Email:   cgwscb2@Lboro.ac.uk

Undergraduate Degree: MEng Chemical Engineering (Loughborough University)

PhD Summary

Purity has the potential to be a limiting factor in cell therapy manufacture. While pre-clinical and lab-scale systems have demonstrated efficacy, the same proportion of product cell purity will be harder to replicate at scale due to the heterogeneity associated with large-scale expansion systems. As such, it is envisaged that an immuno-affinity-based cell purification system will need to be implemented to eliminate unwanted cells. My project is focussed on the development of a scalable hollow fibre membrane (HFM) device for immuno-affinity cell separation to remove unwanted cell types. This is split into two parts:

First, a scaled-down version of the HFM was built and combined with information about the fluid dynamics. In tandem, favourable surface chemistry and antibody modification techniques were employed to maximise cell capacity versus other methods. This enabled critical parameters to be identified and quantified.

The second part involves the use of a quartz microbalance as a cell/protein biosensor and way of extracting information about cell binding kinetics. I have developed a generic model for the latter to aid in the detection of the most influential parameters involved in cell-ligand binding and demonstrated feasibility of the aforementioned interaction within the device. 

The best findings from this are being integrated into a 180 cm3 to evaluate the capacity of the system for cell purification.

Skills & Techniques 

  • Cell therapy process, business and regulatory awareness
  • Appreciation of engineering up- and down-stream challenges facing cell therapy manufacture
  • Surface chemistry / protein modification and immobilisation
  • Chemical characterisation (FTIR/XPS/SEM)
  • Cell culture (MSC, lymphocyte, hESC)
  • Cell isolation/characterisation (magnetic separation, flow cytometry)

 

Publications, Presentations and Awards

Publications

  • M. J. Sawkins, W. Bowen, P. Dhadda, H. Markides, L. E. Sidney, A. J. Taylor,  F. R. A. J. Rose, S. F. Badylak, K. M. Shakesheff, L. J. White. Hydrogels derived from demineralized and decellularized bone extracellular matrix. Acta Biomaterialia. (Pending).

Awards

  • Participated in the 2011 Biotechnology Young Entrepreneur Scheme (Biotechnology YES). The team reached the national finals of the competition.

Future/Career Plans

I am hoping to become involved in a process developmental role within a company or institute.

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