Imperial College London

MrSakhrAlhuthali

Faculty of EngineeringDepartment of Chemical Engineering

Research Postgraduate
 
 
 
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Contact

 

s.alhuthali15

 
 
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Location

 

C611aRoderic Hill BuildingSouth Kensington Campus

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Summary

 

Summary

BEng in Chemical Engineering, University of Newcastle, 2013        

MSc   in Chemical Engineering, University of Manchester, 2014

 

For my CV, linkedin

 

I am a PhD student and my main objective is ‘'Understanding the Interplay Between Upstream and Downstream Bioprocessing by Mathematical Models''.

The production of the recombinant proteins has increased in the last few years because of the improvements that occurred in the upstream process. The main progress is in monoclonal antibody (mAb) production from Chinese hamster ovary cells (CHO), which currently has industrial titer around 10 g/l. At the same time, the process impurities in the fed-batch process have increased as increasing cell density and productivity.The supernatant contains many impurities at different concentrations and properties such as host cell proteins (HCPs), which can be immunogenic or damaging to the product of interest.

The HCPs dynamic profile in the downstream process is affected by many upstream decisions such as the cell line, feeding strategies, environmental conditions. These choices affect the viability and health of cell at harvest which is the main variable to conside regarding the HCPs behaviour in the downstream train.

The industrial disk stack centrifuge has a high energy dissipation rate inlet which may break the cells apart and make the separation more difficult and increase the impurities. The sensitivity to shear stress increses with the cell size. However, the apoptotic cells are the most shear sensitive which usually undergo secondary necrosis.

Using population balance model to analyze the size distributions of the cells at different cell cycle phases G0/G1, S and G2/M would help to understand the suppopulation behavior separately. 

Cell size and rigidity are two main factor to study in the centrifugation separation. Protein A design and operation is a challenging task in mAb purification. An optimal, safe, economic process has to be determined in a very large parameter space that cannot be deeply explored by typical experimentation methodologies. Modelling of these unit operation undoubtedly would minimize the cost and time of understanding the behavior of these impurities.

Multiobjective optimization is the solution to solve the conflict of interests that has affected the HCPs removal efficiency.

Publications