Scale up of optical fractionation for bio-processing

Human pluripotent stem cells are the primary template cells for nearly all the cell types within the body. The exclusivity of these cells arises from their unmatched capability to remain in an unspecialised state until they are induced to differentiate (change from being a stem cell to a cell that has a specific function in the organism). A major challenge of regenerative medicine is to exploit these twin properties to provide wide-ranging novel therapies through the manufacture of beneficial cell types at scale. To date, one of the principal bottlenecks in the development of large scale cell therapies has been the lack of manufacturing-suitable cell separation and purification technologies, effectively limiting the production of products pure enough for wide scale human trials.

This bottleneck is caused by the need for safety and efficacy in sorting cells to high purity without adding antibodies or other modifying agents, in order to remove residual pluripotent cells and also for the identification and definition of the cells in the final product. Hence what regenerative medicine needs in order to be translated into a manufacturing process is a scalable label-free sorting technology. This implies passive sorting which can both be done without labelling and in a highly parallelised manner. However, passive cell sorting technologies require a pathfinder application to fully demonstrate its critical importance to the progression of cell therapy commercialisation. We intend to fulfil this key step by developing scalable passive optical sorting technologies for large scale red blood cell (RBC) manufacture.

The UK has a particularly strong research base in regenerative medicine, yet the opportunities for protecting IP in the development of due to an EU Court of Justice ruling which means that cells derived from human embryonic stem cells (hESCs) cannot be patented. This means that the IP supporting any translation of regenerative medicine involving hESCs will come from the process by which cells are derived (which is still open to patenting). As a result the value of the process is increased, including IP based on manufacturing. Hence, cell sorting techniques developed for regenerative medicine will form the backbone of value creation in hESC derived cell therapies and will be an important mechanism for keeping UK (and European) research competitive with US and Asian competitors.

SOCIETY
The proposed project aims to generate new knowledge and methodologies enabling the production of high quality cells for future application in areas with key societal and economic impact such as regenerative medicine, drug discovery and cancer research. New knowledge allowing the development of scalable processes for cellular therapies will contribute to the eventual clinical translation of cell therapies. The UK is strongly placed in this regard with a world-class knowledge base, key infrastructure, a vibrant commercial environment and an unmatched healthcare system in the form of the National Health Service. In future years the knowledge generated by this work is envisaged to be pivotal in driving the coordinated effort to alleviate the technological, regulatory and policy-making challenges associated with cellular therapies, resulting in a positive impact on the health and well-being of society as well as strengthening the UK's position in this field internationally.

ECONOMY
There is a strong possibility to achieve a positive impact on the economic landscape by commercially exploiting this exciting technology. Optical separation devices are yet to be exploited by the biopharmaceutical or clinical manufacturing communities. This project will debut these devices for scalable cell separation purposes. This will be of huge interest to the cell therapy industry and biopharmaceutical manufacturing industry, and accordingly will generate interest from companies such as Miltenyi Biotech, Pall and GE Healthcare, whose healthcare businesses contain core aspects focused on product separation. In addition, it will offer new methods for value production in the manufacture of stem cell derived therapies, where cell lines based on human embryonic stem cells are not patentable within Europe.

PEOPLE
Along with the investigators, the PDRAs on this project will benefit hugely from its interdisciplinary nature. Working with biologists, physicists and engineers in medical-driven research will lead to career and research opportunities and directions not available in more traditionally discipline-focused projects. The researchers will automatically join the Scottish University Physics Alliance (SUPA), and gain the benefits of networking, collaboration and training offered by this alliance. They will also be encouraged to participate in the Heriot Watt University and the Scottish Crucible training schemes for research leaders. Participation in knowledge transfer networks will also benefit PDRAs by increasing networking and discussion opportunities.

PUBLIC ENGAGEMENT
Dissemination will occur through public and school lectures. Along with our respective group websites, we will publicise this work through activity at the Edinburgh International Science festival and the Dundee Science Centre, with whom Dr MacDonald has a partnership through the Institute for Medical Science and Technology. As the results of this work will be of great interest to the general public, the research team would look to engage with national news and media through the UoD/HWU PR offices to publicise this further.