Date of Graduation
5-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Engineering (PhD)
Degree Level
Graduate
Department
Biological and Agricultural Engineering
Advisor/Mentor
Wickramasinghe, S. Ranil
Committee Member
Qian, Xianghong
Second Committee Member
Nelson, Christopher E.
Third Committee Member
Ulbricht, Mathias
Keywords
Biopharmaceutical; Bioseparations; Membrane
Abstract
The biopharmaceutical industry has developed dramatically in the past decades, alleviating and curing numerous diseases that are not curable with traditional therapies. However, producing biopharmaceuticals is a challenging, complex, and expensive process. Membrane-based technologies have been widely used in biopharmaceutical production, especially downstream processing steps, including clarification, polishing, and other unit operations.
Our research interests focus on the production of two major biopharmaceutical categories: monoclonal antibodies (mAbs) and adeno-associated virus (AAV) vectors. Monoclonal antibodies are the largest class of approved biopharmaceuticals, with more than 130 mAb-based therapies having received regulatory approval in the United States or the European Union. In contrast, AAV-based gene therapy is an emerging but rapidly evolving field. Although there are only five FDA-approved treatments as of June 2024, AAV has attracted considerable research interest due to its potential for gene delivery. Currently, hundreds of AAV-based gene therapies are in various stages of clinical trials.
This study explored the application of membrane technologies for both clarification and polishing steps in producing mAb and AAV capsids. The investigation was divided into four key areas. Firstly, foulants associated with ATF membrane filters employed in mAb production using a perfusion cell culture system were analyzed. Secondly, the removal of mAb aggregates was investigated using environmentally responsive HIC membranes. Thirdly, the clarification of HEK cell lysate for AAV production was achieved using BioOptimal membrane filters in TFF and diafiltration mode to enhance AAV recovery. Finally, the separation of empty and full AAV capsids was examined by applying multimodal AEX membranes.
Citation
Hao, X. (2025). Understanding and Redesigning Membrane-based Unit Operations for Bioseparations. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/5783
