Tending towards Non-fouling: A study of the interaction between proteins and surfaces prepared by radio frequency glow-discharge plasma
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Mecwan, Marvin Magan
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Abstract
All proteins adsorb irreversibly onto surfaces and often results in denaturation, aggregation and loss of activity. This has serious implications not only for medical devices that are used clinically for the treatment of disease but also for the pharmaceutical industry that deals with handling, storage and delivery of protein-based drugs. In this work, we explore radio frequency (RF) glow-discharge plasma technology as a method of creating non-fouling surfaces. We achieve this through two distinct strategies: a) prepare a highly-reactive surface initiators that could be used to grow HEMA polymer brushes via SI-ARGET ATRP, and b) create novel quasi-zwitterionic or mixed-charged surfaces that closely resemble the chemistry of zwitterionic polymers and therefore are capable of reducing protein adsorption. In addition to preparing non-fouling surfaces to prevent protein adsorption, it is also equally important to properly evaluate the surface-protein interaction. This work explores and describes new protocols involving radiolabeling protein studies, radioimmunoassay and substrate-based direct ELISA to better understand the adsorption, retention and changes in biological activity of the protein once it comes in contact with a biomaterial surface, which further informs the biocompatibility of the surface. Finally, we take the lessons learned from using RF glow-discharge plasma to create non-fouling surfaces and developing new protocols to study surface-protein interaction, and apply it to a real world application where we coat hypodermic syringes with a copolymer of HMDSO and MA to prevent protein adsorption while maintaining syringe lubricity. Overall, this research showcases the ability of RF glow-discharge plasma technology to create a variety of non-fouling surfaces that prevents protein adsorption and can be easily clinically translated for a variety of medical applications.
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Thesis (Ph.D.)--University of Washington, 2019
