Date of Award

Spring 4-29-2022

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Master of Science in Biomedical Engineering

Department

Biological Engineering

Advisor

Thomas J. Schwartz

Second Committee Member

Michael D. Mason

Third Committee Member

Karissa Tilbury

Additional Committee Members

Bashir Khoda

Abstract

Traditional cell culture systems make use of two-dimensional (2D) monolayer studies which are simple, cheap, and have been successful for a various cell types. However, since this does not reflect on the in vivo physiology, studies have branched out to use three-dimensional (3D) cell culture systems. 3D cell culture allows for studies which make use of the cell connectivity, polarity, and tissue architecture. The use of 3D aggregates called spheroids is one of the most common and versatile of these methods. There are various techniques for spheroid formation and chosen technique is often decided based on the decided spheroid use and size. Many of these methods are limited by the quantity, size, and reproducibility of the spheroids. A new method focused on the manufacturability of the process would overcome these issues. By focusing on the manufacturability of the process, spheroids would be able to be produced in larger quantities and consistently sized.

The goal of this study is to manufacture and characterize droplet-on-fiber through a dipping process. The withdrawal of the fiber from a liquid solution will result in a coating due to the balance between the viscous drag and the capillary rise. The thickness of the layer depends upon various parameters of the fluid and dipping process. Above a threshold coating thickness, Rayleigh-Plateau Instability will trigger the formation of droplets. Controlling the process parameters will determine the liquid volume in the droplet and its morphology. Such a simple droplet formation technique will be less resource intensive than existing methods and can produce droplets of various sizes and shapes in a short amount of time.

Extruded polylactic acid (PLA) fiber is considered as the substrate for droplet adherence while alginate solution is used for the dipping fluid. The focus of this work is on the shape fidelity and reproducibility of the droplet formation by varying the dipping fluid composition. The aspect ratio between droplet diameter and wetting length is defined as a quantifiable shape-fidelity index which is reported in this work. By varying the dipping fluid composition, the relationship between the viscosity of the dipping fluid (alginate) and the PLA fiber can be identified. The observations made throughout this thesis will allow for further development of this dipping process, as well as determine the optimal concentration of alginate to achieve reproducible droplets with the desired morphology for cell spheroid formation.

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Title Page Addendum

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