Controlling Protein and Cell Adhesion Through Interfacial Engineering for More Efficient Biomanufacturing
Name
mccue-cmccue-phd-meche-2023-thesis.pdf
Description
Thesis PDF
Size
112.57 MB
Format
Adobe PDF
Checksum (MD5)
73b1f48d01dea0f9ac5a25d8d00a6e82
Author(s)
McCue, Caroline
Advisor(s)
Varanasi, Kripa K.
Date Issued
June 2023
Publisher
Massachusetts Institute of Technology
Abstract
Interfaces between biological and synthetic materials present both challenges and opportunities within biomanufacturing. Protein and cell adhesion to surfaces can be controlled to improve steps in a typical biologic manufacturing process from cell culture to protein separation and purification. Within downstream processes, in protein purification, chromatography columns are used to separate target proteins from the output of a bioreactor. This work explores how crystallization could be used as an alternative purification process, by utilizing functionalized nanoparticles to nucleate protein crystals faster and at lower concentrations. We demonstrate significant improvements in nucleation induction time and nucleation rates using bioconjugate-functionalized nanoparticles. Within upstream processes, in adherent cell culture, cells are typically detached from surfaces using trypsin, an enzyme that can damage sensitive cells, and result in genetic mutations. This work studies how passive surface textures and active coatings can impact cell growth, morphology and adhesion. We show that micropost surfaces can significantly reduce cell-surface adhesion, and how electrically active surfaces can be used to detach cells on demand without the use of trypsin. These interfacial platforms present opportunities to reduce the costs of traditional biomanufacturing processes, reduce damage to cells, and enable new high throughput platforms.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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