Fluid mechanics-based in vitro models for development and disease

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Abstract/Contents

Abstract
What are in vitro models, and why develop them? The phrase "in vitro" originates from Latin for "in glass, " referring to the fact that experiments performed outside a living organism ("in vivo") are commonly done in laboratory glassware. Studies performed in vivo in mammalian model systems such as mice allow scientists to study biological phenomena in the full, complex physiological context of the whole organism and can be useful for understanding the interplay between various organ systems. Yet, this very complexity can complicate the pursuit of pointed scientific questions and muddle cause-and-effect with confounding factors. To address this drawback, development of robust in vitro models allows for the isolation and control of variables of interest when the full physiological context is not necessary. In this thesis, I describe several in vitro model systems that I developed during my doctoral work to study various aspects of human development and disease. A common theme among these systems is the incorporation of fluid mechanics principles to recapitulate human biology. In the first half of this thesis, I describe several in vitro microfluidics-based platforms that I developed for understanding the role of signaling factor, or morphogen, gradients in the spatial patterning of stem cell differentiation. In developing these platforms, I take advantage of properties of fluids at the microscale to generate gradients of both protein and small molecule morphogens across differentiating human pluripotent stem cells (hPSCs). I first compare static and flow-based microfluidic platforms and show that both can be used to achieve spatial patterning of hPSC differentiation. I then develop a 6-day, on-chip platform to mimic the anterior-posterior patterning of the developing human endoderm, using two opposing morphogen gradients generated by the aforementioned static microfluidic device. In the second half of this thesis, I describe an in vitro platform capable of creating model tear films, mimicking the multilayer structure that covers the surface of the human eye and is crucial to ocular health. I use this platform, called the Interfacial Dewetting and Drainage Optical Platform (i-DDrOP), to understand how various factors, including a potential dry eye therapeutic, rh-lubricin, and tunable mucin presentation on supported lipid bilayers, influence thin liquid film stability.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2022; ©2022
Publication date 2022; 2022
Issuance monographic
Language English

Creators/Contributors

Author Cui, Kiara Wenhan
Degree supervisor Dunn, Alexander Robert
Degree supervisor Fuller, Gerald G
Thesis advisor Dunn, Alexander Robert
Thesis advisor Fuller, Gerald G
Thesis advisor Loh, Kyle
Thesis advisor Myung, David
Degree committee member Loh, Kyle
Degree committee member Myung, David
Associated with Stanford University, Department of Chemical Engineering

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Kiara Wenhan Cui.
Note Submitted to the Department of Chemical Engineering.
Thesis Thesis Ph.D. Stanford University 2022.
Location https://purl.stanford.edu/qp227rr7756

Access conditions

Copyright
© 2022 by Kiara Wenhan Cui
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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