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Title:Detection of mass, growth rate, and stiffness of single breast cancer cells using micromechanical sensors
Author(s):Corbin, Elise
Director of Research:Bashir, Rashid
Doctoral Committee Chair(s):King, William P.
Doctoral Committee Member(s):Bashir, Rashid; Wagoner Johnson, Amy J.; Prasanth, Supriya G.; Kong, Hyun Joon
Department / Program:Mechanical Sci & Engineering
Discipline:Mechanical Engineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Micromechanical Sensors
Breast Cancer
Cell Mass
Cell Growth Rate
Cell Stiffness
Long-Term Growth
Abstract:Cancer is an intricate disease that stems from a number of different mutations in a cell. These mutations often control the cellular growth and proliferation, a hallmark of cancer, and give rise to many altered biophysical properties. There exists a complex relationship between the behavior of a cell, its physical properties, and its surrounding environment. Knowledge gleaned from cellular biomechanics can lead to an improved understanding of disease progression and provide methods to target it. There are many studies that look at biophysical changes on a large population level, though there is much information that is lost by treating populations as homogeneous in properties and cell cycle phase. Biophysical studies on individual cells can link mechanics with function through coordination with the cell cycle, which is a fundamental physiological process that is crucial for understanding cellular physiology and metabolism. Development of more precise, reliable, and versatile measurement techniques will provide a greater understanding the physical properties of a cell and how they affect its behavior. Microelectromechanical systems (MEMS) technology can provide tools for manipulating, processing, and analyzing single cells, thus enabling detailed analyses of their biophysical properties. Growth is a vital element of the cell cycle, and cell mass homeostasis ensures that the cell mass and cell cycle transitions are coordinately linked. An accurate measurement of growth throughout the cell cycle is fundamental to understanding mechanisms of cellular proliferation in cancer. Growth can be identified through many ways; however, cell mass has been unexplored until the recent development of cantilever-type MEMS devices for mass sensing through resonant frequency shift. Measuring the dependency of growth rate on cellular mass may help explain the coordination and regulation of the cell cycle. However, MEMS mass sensing devices still require further development and characterization in order to reliably investigate long-term cell growth over the duration of the cell cycle. This dissertation focuses on the use of MEMS resonant pedestal sensors for measuring the mass and growth rate of single cancer cells. This work included characterization and improvement of the sensors to address current challenges in the measurement of long-term growth rate. The MEMS resonant pedestal sensors were first used to measure physical properties of biomaterials, including the micromechanical properties of hydrogels through verification of stiffness effect on mass measurements. Before studying live cells, modifications to the fabrication process were introduced to improve cell capture and retention. These include integration of an on-chip microfluidic system for delivery of fluids during mass measurements and the micro-patterning of sensor surfaces for select functionalization and passivation. These modifications enable long-term measurement of the changes in mass of normal and cancerous cells over time. This is the first investigation of the differences in growth rate between normal and cancer cells using MEMS resonant sensors.
Issue Date:2014-01-16
Rights Information:Copyright 2013 Elise Anne Corbin
Date Available in IDEALS:2014-01-16
Date Deposited:2013-12

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