Microfluidic, gradient-generator devices as in vitro mimics of cellular microenvironments

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The larger goal of this work is to engineer an appropriate in vitro platform to understand the complex interplay of various effectors in vivo. The specific approach taken was to develop and utilize microfluidic devices to study the impact of stable soluble biochemical gradients on cellular behaviors. Microfluidic devices are tools capable of recreating many critical aspects of the natural microenvironments of cells and tissues in a controllable and reductionist manner. Several microfluidic device geometries were evaluated through computational finite element modeling and experimental characterization studies to produce predictable and stable concentration gradients over multiple days of cell culture. We implemented these helpful devices in order to study the mechanism of cellular responses to various biochemical and biomechanical factors in both two and three dimensions for several cellular applications. First, this device was used to perform an in depth study of the complex interplay between soluble biochemical and biomaterial effectors of endothelial cell sprouting. The sprouting of endothelial cells into capillary-like structures is an early critical step in angiogenesis, the formation of new blood vessels from existing conduits. Time-lapse microscopic images of endothelial sprouts within the devices were quantified to determine the role of matrix density in regulating sprout initiation, elongation, and navigation. Matrix density was found to have profound effects on sprout kinetics, morphology, and alignment within gradients of vascular endothelial growth factor. Use of these novel microfluidic devices was expanded to include proof-of-concept experiments demonstrating the high-throughput screening of multiple engineered biomaterials to identify scaffold properties conducive to endothelial network formation. Finally, the microfluidic devices were utilized in preliminary studies of neuronal cell behavior within gradients of various neurotrophins and bone marrow derived mast cell chemotaxis within gradients of Kit ligand. Taken together, the results of this thesis demonstrate the usefulness of microfluidic devices as well-controlled in vitro culture platforms capable of creating stable, soluble biochemical gradients. Furthermore, these devices may lead to future techniques to provide directional cues during cell and tissue growth for regenerative medicine applications. For example, our results may be useful for developing potential pro- and anti-angiogenic therapeutic strategies for clinical treatment of ischemia and cancer, respectively.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Copyright date 2011
Publication date 2010, c2011; 2010
Issuance monographic
Language English


Associated with Shāmlū, Amīr
Associated with Stanford University, Department of Mechanical Engineering
Primary advisor Heilshorn, Sarah
Thesis advisor Heilshorn, Sarah
Thesis advisor Barron, Annelise E
Thesis advisor Shaqfeh, Eric S. G. (Eric Stefan Garrido)
Advisor Barron, Annelise E
Advisor Shaqfeh, Eric S. G. (Eric Stefan Garrido)


Genre Theses

Bibliographic information

Statement of responsibility Amir Shamloo.
Note Submitted to the Department of Mechanical Engineering.
Thesis Thesis (Ph.D.)--Stanford University, 2011.
Location electronic resource

Access conditions

© 2011 by Amir Shamloo

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