Impedance based sensing principles for microfluidic lab-on-a-chip systems: Application to cell volume assays
Ateya, Daniel A
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The rapidly developing field of lab-on-a-chip systems aims at combining various microfluidic components in the construction of fully functional, self-contained devices for robust, portable, large-scale integrated chemical and biological processing and analysis. To-date such devices have demonstrated applications in fundamental cellular and microbiology studies, analytical and combinatorial chemistry for drug discovery and high throughput screening, point-of-care and clinical diagnostics, genomics, proteomics as well as systems for detection of bio-warfare and chemical warfare agents. Existing microfluidic components remain limited in their capabilities, ease of integration, and scope. This work aimed to expand the field by demonstrating innovative techniques that confer functionality without sacrificing simplicity and ease of integration in lab-on-a-chip systems. Impedance-based techniques were developed to monitor volume changes of a sensing element in a microfluidic channel; allowing detection of various useful parameters in a lab-chip. Two systems were designed, fabricated, and tested to demonstrate the principle. The first used an electrolytic bubble sensing element; which is a direct extension of bubble-based microfluidic technologies. The second system relied on biological cells as sensing elements in a microfluidic channel. As such, this work broadly evolved from impedance-based sensing techniques that can be used for closed-loop control of fluid handling components to robust applications in cell-based microfluidic assays. In this thesis, device design considerations, fabrication techniques and characterization are presented. Fundamental studies of bubble growth, dynamics and configuration in a microchannel are described providing the basis for a bubble sensor which can detect effects of pressure and interfacial tension in a microfluidic system. The significance and fundamental principles of cell volume are discussed followed by the development and characterization of a microfluidic cell volume sensor. Using primary rat astrocytes and E. coli , various applications of the sensor are demonstrated, including the ability to study cell volume regulation, screen bioactive reagents and the effects of pharmaceuticals on mammalian and bacterial cells.