High signal-to-noise ratio (SNR) is typically required for higher resolution and faster speed in magnetic resonance imaging (MRI). Planar microcoils as receiver probes in MRI systems offer the potential to be configured into array elements for fast imaging as well as to enable the imaging of extremely small objects. Microcoils, however, are thermal noise dominant and suffer limited SNR. Cryo-cooling for the microcoils can reduce the thermal noise, however conventional cryostats are not optimum for the microcoils because they typically use a thick vacuum gap to keep samples to be imaged to near room temperature during cryo-cooling. This vacuum gap is typically larger than the most sensitive region of the microcoils that defines the imaging depth, which is approximately the same as the diameters of the microcoils. Here microfluidic technology is utilized to locally cryo-cool the microcoils and minimize the thermal isolation gap so that the imaging surface is within the imaging depth of the microcoils. The first system consists of a planar microcoil with microfluidically cryo-cooling channels, a thin N2 gap and an imaging. The microcoil was locally cryo-cooled while maintaining the sample above 8°C. MR images using a 4.7 Tesla MRI system shows an average SNR enhancement of 1.47 fold. Second, the system has been further developed into a cryo-cooled microcoil system with inductive coupling to cryo-cool both the microcoil and the on-chip microfabricated resonating capacitor to further improve the Q improvement. Here inductive coupling was used to eliminate the physical connection between the microcoil and the tuning network so that a single cryocooling microfluidic channel could enclose both the microcoil and the capacitor with minimum loss in cooling capacity. Q improvement was 2.6 fold compared to a conventional microcoil with high-Q varactors and transmission line connection. Microfluidically tunable capacitors with the 653% tunability and Q of 1.3 fold higher compared to a conventional varactor have been developed and demonstrated as matching/tuning networks as a proof of concept. These developed microfluidically cryo-cooling system and tunable capacitors for improving SNR will potentially allow MR microcoils to have high-resolution images over small samples.

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Recent advances in micro technologies have equipped researches with novel tools for interacting with biological molecules and cells. This thesis focuses on the design, fabrication and application of microfluidic platforms for stimuli-responsive drug delivery and the electromechanical characterization of single cells. Stimuli-responsive hydrogels are promising materials for controlled drug delivery due to their ability to respond to changes in local environmental conditions. In particular, nanohydrogel particles have been a topic of considerable interest due to their rapid response times compared to micro and macro-scale counterparts. Owing to their small size and thus low drug-loading capacity, these materials are unsuitable for prolonged drug delivery. To address this issue, stimuli-responsive implantable drug delivery micro devices by integrating microfabricated drug reservoirs with smart nano-hydrogel particles embedded composite membranes have been proposed. In one proposed glucose-responsive micro device, crosslinked glucose oxidase enables the oxidation of glucose into gluconic acid, producing a microenvironment with lower pH values to modulate the pH-responsive nanoparticles. In vitro glucose-responsive drug release profiles were characterized and normoglycemic glucose levels in diabetic rats with device implantation were also recorded. The biophysical properties of single cells have recently been demonstrated as an important indicator of disease diagnosis. Existing technologies are capable of characterizing single parameter either electrical or mechanical rapidly, but not both, which could only collect limited information for cell status evaluation. To address this issue, two microfluidic platforms capable of simultaneously characterizing both the electrical and mechanical properties of single cells based on electrodeformation and integrated impedance spectroscopy with micropipette aspiration have been proposed. In one proposed microfluidic device, a negative pressure was used to suck cells continuously through the aspiration channel with impedance profiles measured. By interpreting impedance profiles, transit time and impedance amplitude ratio can be quantified as cellular mechanical and electrical property indicators. Neural network based cell classification was conducted, demonstrating that two biophysical parameters could provide a higher cell classification success rate than using electrical or mechanical parameter alone.

The embryonic stem cell (ESC) microenvironment contains various localized physical and biochemical cues to direct cell fate. Current approaches for microenvironmental regulation rely on restricting cell behaviour to control endogenous signals such as secreted ligands. This report presents a microfluidic device that can directly manipulate the removal of autoregulatory ligands from culture and control the activation of Signal Transducer and Activator of Transcription-3 (Stat3) in ESCs. Specifically, the response of Stat3 was measured under diffusive and convective mass transfer regimes. A Brownian dynamics algorithm was also developed to simulate ligand transport and predict cellular response under these conditions. Stat3 activation under perfusion culture was found to depend on flow rate and axial distance in the flow direction. Long-term perfusion also allowed for the formation of a sustained gradient of Stat3 activation that led to selective loss of ESC pluripotency. These results demonstrate the utility of microfluidic culture for stem cell bioengineering applications.

This research focuses on the detection and characterization of cells using impedance-based techniques to understand the behavior and response of cells to internal/environmental changes. In combination with impedimetric sensing techniques, the biosensors in this work allow rapid, label-free, quantitative measurements and are very sensitive to changes in environment and cell morphology. The biosensor design and measurement setup is optimized to detect and differentiate cancer cells and healthy (normal) cells. The outcome of this work will provide a foundation for enhanced 3-dimensional tumor analysis and characterization; thus creating an avenue for earlier cancer detection and reduced healthcare costs. The magnitude of cancer-related deaths is a result of late-diagnosis and the fact that cancer is challenging to treat, due to the non-uniform nature of the tumor. In order to characterize and treat individual cells based on their malignant potential, it is important to have a measurement technique with enhanced spatial resolution and increased sensitivity. This requires the study of individual or small groups of cells that make up the entire tissue mass. The overall objective of this research is to optimize a microelectrode biosensor and obtain statistically relevant data from a cell culture using an independent multi-electrode design. This would provide a means to explore the feasibility of electrically characterizing cells with greater accuracy and enhanced sensitivity.

This thesis focuses on the development of two new applications using ion concentration polarization (ICP): an out-of-plane microfluidic approach for water desalination and a method for concentration and transportation of charged analytes in paper-based biomedical diagnostic device. In the first work, we present an out-of-plane desalination approach using ICP. A depletion boundary separates salt ions and purified water into distinct vertically stacked layers. The out-of-plane design enables multiplexing in three dimensions, providing the functional density required for practical applications. The second work demonstrates an active control mechanism of target analytes in paper using ICP. Both external devices (with all functional units on one side of paper) and integrated paper microfluidic devices (by embedding all functional units in paper) were developed to concentrate and transport charged analyte molecules in the paper. We also demonstrate a new fabrication method of nanofluidic and hydrophobic barriers (nanoporous membrane patterning) in paper microfluidic device.

The incorporation of active piezoelectric elements and fluidic components into micro-electromechanical systems (MEMS) is of great interest for the development of sensors, actuators, and integrated systems used in microfluidics. Low temperature cofired ceramics (LTCC), widely used as electronic packaging materials, offer the possibility of manufacturing highly integrated microfluidic systems with complex 3-D features and various co-firable functional materials in a multilayer module. It would be desirable to integrate high performance lead zirconate titanate (PZT) based ceramics into LTCC-based MEMS using modern thick film and 3-D packaging technologies. The challenges for fabricating functional LTCC/PZT devices are: 1) formulating piezoelectric compositions which have similar sintering conditions to LTCC materials; 2) reducing elemental inter-diffusion between the LTCC package and PZT materials in co-firing process; and 3) developing active piezoelectric layers with desirable electric properties. The goal of present work was to develop low temperature fired PZT-based materials and compatible processing methods which enable integration of piezoelectric elements with LTCC materials and production of high performance integrated multilayer devices for microfluidics. First, the low temperature sintering behavior of piezoelectric ceramics in the solid solution of Pb(Zr0.53,Ti0.47)O3-Sr(K0.25, Nb0.75)O3 (PZT-SKN) with sintering aids has been investigated. 1 wt% LiBiO2 + 1 wt% CuO fluxed PZT-SKN ceramics sintered at 900oC for 1 h exhibited desirable piezoelectric and dielectric properties with a reduction of sintering temperature by 350oC. Next, the fluxed PZT-SKN tapes were successfully laminated and co-fired with LTCC materials to build the hybrid multilayer structures. HL2000/PZT-SKN multilayer ceramics co-fired at 900oC for 0.5 h exhibited the optimal properties with high field d33 piezoelectric coefficient of 356 pm/V. A potential application of the developed LTCC/PZT-SKN multilayer ceramics as a microbalance was demonstrated. The final research focus was the fabrication of an HL2000/PZT-SKN multilayer piezoelectric micropump and the characterization of pumping performance. The measured maximum flow rate and backpressure were 450 μl/min and 1.4 kPa respectively. Use of different microchannel geometries has been studied to improve the pumping performance. It is believed that the high performance multilayer piezoelectric devices implemented in this work will enable the development of highly integrated LTCC-based microfluidic systems for many future applications.

This thesis seeks to address the critical bottlenecks of current technologies that have slowed the neuroscience research in C. elegans. The objective of this research is to enhance the currently developed systems through the design and construction of simple microdevices and quantitative analytical tools for high-throughput phenotyping C. elegans to investigate functions of nervous systems. First, we developed and used the integrated system combining user-friendly single-layer microfluidics and quantitative analytical tools to study the genetic regulation of target gene expression. We found several putative mutants based on large-scale screens, which would have previously been too labor-intensive to attempt. Second, we developed a simple mathematical model that describes the regulation of a target gene expression. Using the model developed, we simulated phenotypical space of hypothetical mutants to suggest plausible genetic pathways some isolated mutants may affect. Lastly, we developed a high-density multichannel device for rapid trapping, parallel selective stimulating, long-term culturing, and (often repeatedly). We used this integrated system to study the neurodegenerative process based on selective ablation of multiple animals using an optogenetic tool, which would have been taken at least 1 order of magnitude longer. Taken together, we expect that these developments will greatly facilitate a broad range of fundamental, and application studies including aging, neurodegeneration, circuit and behavior.

In this PhD thesis, the nano-opto-mechanical system (NOMS) is explored and two nano-opto-mechanical devices are designed, analyzed, simulated and fabricated. Firstly, an angular momentum generator consisting of a ring resonator, a wave guide and a group of nano-rods is designed, theoretically analyzed and simulated. The theoretic alanalysis and numerical results show that a series of rotating optical field (ROF) are generated when different resonant wave lengths are coupled into the generator. Subsequently, the optical force, the optical potential and the optical torque of the generated ROF are theoretically analyzed, numerically simulated and discussed. The optical force distributions are affected by the ROF with different angular orders and different objects. The optical torques are analyzed and discussed for different objects, i.e. spherical nano-particle, nano-wire and nano-rotor. Finally, a tunable coupled-resonator-induced transparency (CRIT) system, which is driven by the optical force between the ring resonator and the substrate, is designed, theoretically analyzed, simulated, fabricated and experimented. The tunable CRIT system consists of a bus wave guide and two coupled ring resonators, in which one is the released ring and the other is the fixed ring. Different input powers produce different optical forces on the released ring, which produce different final deformations, change the optical field buildup, shift the transmission spectrum and vary the group delay

For the past two decades, flow cytometry has been widely used as a powerful analysis tool for the diagnosis of many diseases due to its ability to count, characterize and sort cells. However, conventional flow cytometers are often bulky, expensive and complicated because sophisticated fluidic, electronic and optical systems are required to realize the functions of flow cytometry. The high cost and the complexity in operation and maintenance associated with flow cytometers as well as the large size have limited its use. In recent years, the rapid development of microfluidics-based lab-on-a-chip technology has created a new pathway for flow cytometry. Microfluidic devices allow for the integration of multiple liquid handling processes required in the diagnostic assays, such as pumping, metering, sampling, dispensing, sequential loading and washing. These lab-on-a-chip solutions have been recognized as an opportunity to bring portable, accurate and sensitive diagnostic tests to the flow cytometry. However, most current microfluidic flow cytometry devices are micro- only in the microfluidic chip, the rest of most apparatuses are still large and costly, usually involving tubes, microscopes, lasers and mechanical pumps. Therefore, the objective of this study is to develop a novel lab-on-a-chip system based on the electrokinetically-induced pressure-driven flow and dual-wavelength fluorescent detection, which lights a promising pathway for making a real portable, compact, low-cost microfluidic flow cytometry device. In this study, the core of this microfluidic system is the custom-designed PDMS (polydimethylsiloxane) microchip. A novel method was applied to generate the electrokinetically-induced pressure-driven flow in a T-shaped microchannel using parameters settings that had been optimized by numerical study. This method combined both the electrokinetic pumping force and the pressure pumping force to eliminate their shortcomings associated with the use of each force alone. This is the fundamental of my study. By using this microchip, the size of the fluidic control subsystem is reduced significantly. Furthermore, the dual-wavelength fluorescent detection strategy is proposed in this thesis. On the optical detection side, excitation lights of two different wavelengths are provided by a single LED (light-emitting diode) from one side of the microchannel. Then the two emission lights are captured individually by two photo-detectors placed on the top and the bottom of the microchip. Compared with other microfluidic detection devices reported in the literatures that use lasers or PMTs (Photomultiplier tubes), this design allows for a significant reduction of 90% in the volume and cost. As another important part of my thesis research, a novel flow focusing method that allows the hydrodynamic focusing in a T-shaped microchannel with two sheath flows is developed. This method solves the biggest obstacle which exists in current microfluidic flow cytometry devices. In this method, no external pumps, valves and tubing are involved in the system. Although substantial progress has been made in current microfluidic flow cytometry, there is still a need for a low-cost, compact, portable microfluidic devices, especially in low-resource settings as well as the developing world for POC (point-of-care) diagnosis and analysis. This thesis work has made a great achievement towards the final goal.