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PhD project title

Microfluidic approach for Continuous biopharmaceutical crystallisation

Outline description, including interdisciplinary, intersectoral and international dimensions 

The worldwide demand for biotechnologically produced proteins is growing significantly. To satisfy this growth, production processes have been optimised for higher concentration by significant progress in cell culture and recombinant technologies. However, these increased yields have created a bottleneck in the downstream processing, which currently relies on complex, inefficient and expensive separation stages, traditionally operated in batch-mode. Crystallisation is a cost effective and easily scalable purification technique for the recovery of target products. The solid-crystalline state affords for higher product activity, stability and a sustained release capability (bioavailability) relative to liquid-based formulations or amorphous freeze-dried solids. Nevertheless, crystallisation of protein is intrinsically more difficult and uncertain than for small molecules, particularly from complex mixtures, due to their large molecular weights, structural complexities and the presence of impurities. Microfluidic devices provide many advantages for protein crystallisation; they require small sample volumes, provide high-throughput screening, and allow control of the protein crystallisation. Microfluidics is a multidisciplinary field of science based on the manipulation of fluids in sub-millimetre dimensions, and the conditions that microfluidics offer are completely different from those of bulk set-ups, and thus they are very interesting for the study of crystallisation because diffusion, mixing, mass and heat transport, can controlled. In order to prepare novel highly complex microfluidic devices, a single-step, rapid, and cost-effective protocols will be prepared, using in-house fabrication of microfluidic devices by 3D printing and soft photolithography. Multiphysics simulations of the microfluidic devices using finite element methods (FEM) will take place in order to enable the study of microfluidic phenomena in the chips and optimise the designs. On this premise: Innovative “pharma-on-a-chip” continuous microfluidic devices for protein crystallisation will be designed and fabricated in collaboration with engineering in Queen’s and protein engineers in Immunocore. The research activity is of multidisciplinary nature and includes contributions from molecular & cell biology (Immunocore), pharmaceutical science, design and fabrication of new microfluidic devices (Dr Lamprou) and FEM (Dr Abdelal).

The student will have the opportunity to spend time to Immunocore (industrial collaborator) and also we will offer the opportunity to spent time at University of Pavia (Italy) and will attend minimum one conference per year. Therefore, the  results will lead to publications in appropriate high impact journals (e.g. Journal of Controlled Release, Biomaterials etc.) and the work would also be disseminated to the academic community via international conferences

Dr Lamprou is the Co-Investigator in the Horizon 2020 Revolutionising Downstream Processing of Monoclonal Antibodies by Continuous Template-Assisted Membrane Crystallization (AMECRYS - €3.6M; http://www.amecrys-project.eu/) and the candidate of this project will also joined as member this EU multidisciplinary consortium.

Key words/descriptors

 

 

Microfluidic devices, protein crystallisation, advanced characterisation, biopharmaceuticals, 3D printing.

Fit to CITI-GENS theme(s)

 

  • Advanced Manufacturing,
  • Life Sciences

Supervisor Information

 

 

First Supervisor: Dr Dimitrios Lamprou                                             School: School of Pharmacy

Second Supervisor: Dr Gasser Abdelal                                               School: School of Mechanical and Aerospace Engineering

Third Supervisor: Dr Shahid Uddin                                                      Company: Immunocore

Name of non-HEI partner(s)

3rd Supervisor

Name: Dr Shahid Uddin,

Shahid is the Director of Drug product, formulation & stability at Immunocore, responsible for development for antibody and peptide and therapeutics, encompassing new novel formats. Shahid has supervised over 20 Ph.D. and Postdocs, and his experience involves both early stage formulation development as well as late stage development as both liquid and lyophilized presentations. His group also have experience of several types of drug delivery technologies including discovery and protein engineering.

Non-HEI: Immunocore Limited Oxford, UK

Contribution of non-HEI partner(s) to the project:

 

 

Contribution on non-HEI partner: Immunocore will provide placements, consumables during the visits, and also the cost of traveling from Belfast to Oxford. The candidate will be assigned to a team of passionate professionals and have the opportunity to use the developed microfluidic devices in Queen’s for the manufacturing of protein crystals using the developed therapeutic bioformulations from the worldwide biologists in Immunocore. The candidate will also be introduced to routine sub-culture of cells and protein engineering.

 

Profile of the non-HEI partner and the nature of the relationship.    

 

Expertise of Collaboration: Immunocore has an Immtac discovery and protein engineering department that applies cutting-edge technologies in the discovery of novel therapeutic biologics to change the lives of patients. The collaboration with QUB will provide the opportunity to use new technologies (e.g. microfluidics) for the formulation of biopharmaceuticals that will be cheaper and faster to be produced, including for personalised medicine.

Vision Shared with CITI-GENS: Immunocore vision is to train new scientist and placed new cheaper biopharmaceutical products in the market that will help society and be specific for each individual and disease.

Research centre / School

Pharmacy

Subject area

Pharmaceutical Technology, Biopharmaceutics, Industrial Biopharmaceutics