Development of a Dielectrophoresis-Based Cancer-Cell Analysis Tool

Douglas, Temple Anne

Development of a Dielectrophoresis-Based Cancer-Cell Analysis Tool

dc.contributor.author	Douglas, Temple Anne	en
dc.contributor.committeechair	Davalos, Rafael V.	en
dc.contributor.committeemember	Verbridge, Scott	en
dc.contributor.committeemember	Schmelz, Eva M.	en
dc.contributor.committeemember	Stremler, Mark A.	en
dc.contributor.committeemember	Cimini, Daniela	en
dc.contributor.department	Biomedical Engineering and Mechanics	en
dc.date.accessioned	2018-10-05T08:00:20Z	en
dc.date.available	2018-10-05T08:00:20Z	en
dc.date.issued	2018-10-04	en
dc.description.abstract	One significant obstacle in cancer treatment is tumor heterogeneity. Different subpopulations within a tumor can respond differently to chemotherapy, resulting in resistance and recurrence. Addressing these differences while choosing a treatment modality could significantly improve chemotherapy outcomes. This work focuses on the development of a new modular device that leverages the unique advantages of a contactless dielectrophoresis, a method that uses applied electric fields in a microfluidic device to separate cells by biophysical phenotype. By optimizing force balancing between the dielectrophoretic force and the drag force on cells in the device, and by using cell-size pillars to maximize electric field gradients per volt applied while reducing cell-cell interactions,we demonstrate that it is possible to separate mouse ovarian surface epithelial (MOSE) cells at different stages while maintaining high viability. We also show other cell types to be separable with this device and develop an algorithm to rapidly analyze cell response to a variety of frequency/voltage/flow rate combinations. We also propose a microfluidic device downstream of the DEP chip that can be used to provide an integrated system for studying the subpopulations separated using dielectrophoresis by moving them into a culture chamber with hydrogel where they can be grown in 3D and characterized for a variety of parameters such as biophysical structure, metastatic capacity, and chemotherapy resistance.	en
dc.description.abstractgeneral	Dielectrophoresis is a method by which cells are polarized in response to an electric field gradient. This work optimizes this technique so that it can be used to separate highly similar subpopulations of cancer cells in a microfluidic device. Computer code is also developed to automate data processing. A technique for analyzing these cell subpopulations is also proposed and some feasibility testing performed.	en
dc.description.degree	Ph. D.	en
dc.format.medium	ETD	en
dc.identifier.other	vt_gsexam:17223	en
dc.identifier.uri	http://hdl.handle.net/10919/85239	en
dc.publisher	Virginia Tech	en
dc.rights	In Copyright	en
dc.rights.uri	http://rightsstatements.org/vocab/InC/1.0/	en
dc.subject	dielectrophoresis	en
dc.subject	biophysics	en
dc.subject	metastasis	en
dc.subject	evolution	en
dc.subject	cancer	en
dc.subject	treatment resistance	en
dc.title	Development of a Dielectrophoresis-Based Cancer-Cell Analysis Tool	en
dc.type	Dissertation	en
thesis.degree.discipline	Biomedical Engineering	en
thesis.degree.grantor	Virginia Polytechnic Institute and State University	en
thesis.degree.level	doctoral	en
thesis.degree.name	Ph. D.	en