Cancer is a major health issue that has been associated with over 80 million deaths worldwide in the last decade. Recently, significant improvements have been made in terms of treatment and diagnosis. However, despite these advancements there is still a demand for low-cost, high-accuracy, and easy-to-use technologies capable of classifying cells. Analysis of cell behavior in microfluidic deformability assays provides a label-free method of observing cell response to physical and chemical stimuli. This body of work shows advancements made toward reaching our goal of a robust and cost-effective biosensing device that allows for the identification of normal and cancer cells. These devices can also monitor cell responses to physical and chemical stimuli in the form of mechanical deformation and chemotherapeutic drugs, respectively. Our initial design was a microfluidic device that consisted of three channels with varying deformation and relaxation regions. Cell velocities from the deformations regions allowed us to distinguish between normal and cancer cells at the single-cell level. The next design used a singular deformation channel that was embedded with an array of electrodes in order to measure entry time, transit time and velocities as a single cell passes through the channel. These factors were found to reveal information about the biomechanical properties of single cells. Embedded electrodes were implemented in order to reduce post processing times of the data analysis and provide more insight into the bioelectrical information of cells. Finally, we report a microfluidic device with parallel deformation channels and a single electrode pair to improve throughput and automate data collection of deformability assays. This thesis demonstrates how microfluidic deformability assays, with and without embedded electrodes, show promising capabilities to classify different cells based on their biophysical traits which can be utilized as a valuable tool for testing responses to physical and chemical stimuli. / MS / Cancer is a worldwide health issue with approximately 1.7 million new cases each year in the United State alone. Although a great amount of research has been conducted in this field, the numerous uncertainties and heterogeneity among tumors, which is amplified by the large diversity between patients, has limit progress in both diagnostics and therapy. Traditionally, cancer studies have primarily focused on biological and chemical techniques. However, more recently, researchers have begun to leverage engineering techniques to acquire a new perspective on cancer to better understand the underlying biophysical attributes. Thus far, various engineering methodologies have produced meaningful results, but these techniques are costly and tend to be laborious. As a result, there is a need for low-cost, high-accuracy, and easy-to-use technologies to aid with cancer research, diagnostics, and treatment. An emerging field to alleviate these concerns is microfluidics, which is a science involving the flow of fluids in micro-scale channels. The field of microfluidics shows a great deal of promise for the development of clinically ready devices for analyzing cancer cells at both the population and single cell levels. Investigating the behavior of cancer cells at a single cell level can provide valuable information to help better understand the responsiveness of tumors to physical or chemical stimuli, such as chemotherapeutic drugs. This thesis reports multiple robust and cost-effective biomedical micro-devices that are used to analyze normal and cancerous cells. These devices consist of a microfluidic channel with sensors and are created using micro-fabrication techniques. The unique designs have enabled the evaluation of cells based on their mechanical and electrical properties. Specifically, the mechanical properties can be measured by forcing a cell into a microfluidic channel that is smaller than the diameter of the cell and recording its response to this physical stimulus. Electrical properties are measured simultaneously as the cells are probed for their mechanical properties. In general, the mechanical and electrical properties of cells can be altered when they undergo internal change (i.e. diseased cells) or experience external stimuli. Thus, these properties can be utilized as indicators of cancer progression and can be used to distinguish tumorigenic from non-tumorigenic cells. Data collection from these devices is automated, allowing for the rapid acquisition of mechanical and electrical properties of cells with minimal post-processing. Results from these devices have been promising in their ability to indicate significant differences among various normal and cancer populations based on their mechanical and electrical attributes.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/89947 |
| Date | 19 December 2017 |
| Creators | Ghassemi, Parham |
| Contributors | Electrical Engineering, Agah, Masoud, Zhu, Yizheng, Zhou, Wei |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/x-zip-compressed |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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