Date of Award

1-1-2014

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Nanoscale Science and Engineering

Program

Nanoscale Engineering

Content Description

1 online resource (x, 145 pages) : color illustrations.

Dissertation/Thesis Chair

James Castracane

Committee Members

J. Andres Melendez, Susan Sharfstein, Ben Szaro, Scott Tenenbaum

Keywords

AFM, Cancer, Chemotaxis, Hypoxia, Impedance Spectroscopy, NANIVID, BioMEMS, Nanomedicine, Tumors

Subject Categories

Biomedical Engineering and Bioengineering | Nanoscience and Nanotechnology

Abstract

The tumor microenvironment has been demonstrated to be a key determinant in the progression of cancer. Unfortunately, the mechanisms behind the different microenvironments (cytokine gradients, hypoxia, hypoglycemia, etc) have not been fully elucidated. Identifying these mechanisms can lead to targeted, individualized therapy to prevent metastasis. The Nano Intravital Device (NANIVID) is a microfabricated, implantable device designed to initiate specific microenvironments in vivo so that the time course of the effects can be observed. With both spatial and temporal control over the induced environments, the affected regions of the tumor can be compared to the rest of the tumor. The NANIVID was first used to establish cytokine gradients to monitor the migration of invasive cancer cells. The three projects that comprise this work expand the applications of the NANIVID to establish the device as a robust platform for investigating tumor microenvironment interactions. The first project released chemical mimics from the device to induce the cellular hypoxic response in tumors to determine how hypoxia affects the fate of disseminated tumor cells. The second project used the NANIVID in combination with an atomic force microscope to investigate the altered mechanics of migrating invasive cancer cells. The final project was to develop a cell counter to monitor the isolation of the invasive subpopulation of cells that were drawn into the device using a chemoattractant. These three projects demonstrate the potential of the NANIVID as a platform for investigating the tumor microenvironment.

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