Date of Award

2020

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Chemical Engineering (PhD)

Administrative Home Department

Department of Chemical Engineering

Advisor 1

Caryn L. Heldt

Committee Member 1

David Shonnard

Committee Member 2

Loredana Valenzano-Slough

Committee Member 3

Silviya Petrova Zustiak

Abstract

Viral infections regularly pose detrimental health risks to humans. Preventing viral infections through global immunization requires the production of large doses of vaccines. The increasing demand for vaccines, especially during pandemics such as COVID-19, has challenged current manufacturing strategy to develop advanced unit operations with high throughput capability. Over the decade, the upstream processing responsible for synthesizing viral products in cell cultures has shown significant success in yielding high titers of viruses and virus-like particles. The progress in the upstream stage has now shifted the bottleneck to the downstream processing (DSP). Overlooked for decades, the DSP responsible for viral product purification from the cell culture contaminants requires a makeover with the development of new purification strategies and an upgrade in the traditional unit operations. The current DSP train employing chromatography and filtration methods have been suboptimal in efficiently processing comparatively complex and fragile viral particles. Thus, the lack of platform technology for viral vaccine and biotherapeutic DSP has led to a search for alternative and innovative methods that have not only high-throughput capabilities but also have potential for continuous operation.

In the pool of potential technologies, aqueous two-phase system (ATPS) has shown to be a promising candidate with the numerous advantages over conventional methods. However, an unambiguous and complex biomolecule partitioning mechanism has required a large experimental setup for optimizing virus purification. This work focused on a framework utilizing a phase diagram of a rationalized polyethylene glycol-citrate system to optimize virus purification. The partitioning behavior of two non-enveloped viruses, porcine parvovirus (PPV) and human rhinovirus-14 (HRV), were studied in various system compositions. A tie-line length framework was utilized to define the systems and relate the partitioning behavior of viruses with different surface physicochemical characteristics.

Available for download on Sunday, February 28, 2021

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