Browsing by Subject "Microfabrication"
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Item Advancements In Microfluidics For Biotechnology Applications(2018-10) Agrawal, PranavMicrofluidic technology has made a huge impact in the field of biotechnology and life sciences. The advancements can be categorized into three aspects: understanding of physical phenomena at the microscale; development of tools for easy integration of different phenomena; and devising systems for various applications. This thesis highlights the ability of microfluidic technology in manipulating different biological entities by fabricating small feature sizes. In particular, we have focused on the development of new processes for three biotechnology applications – (i) long DNA sample preparation for genomic; (ii) delivery of genetic delivery vehicles for gene and cell therapy; and (iii) an in vitro model to study human gut. Each of these systems is developed in close collaboration with potential users and is aimed towards easy integration with the existing workflow. Long-read genomic applications such as genome mapping in nanochannels require long DNA that is free of small-DNA impurities. Chapter 2 reports a chip-based system based on entropic trapping that can simultaneously concentrate and purify a long DNA sample under the alternating application of an externally applied pressure (for sample injection) and an electric field (for filtration and concentration). In contrast, short DNA tends to pass through the filter owing to its comparatively weak entropic penalty for entering the nanoslit. The single-stage prototype developed here, which operates in a continuous pulsatile manner, achieves selectivity of up to 3.5 for λ-phage DNA (48.5 kilobase pairs) compared to a 2 kilobase pair standard based on experimental data for the fraction filtered using pure samples of each species. The device is fabricated in fused silica using standard clean-room methods, making it compatible for integration with long-read genomics technologies. Non-viral delivery vehicles are becoming a popular choice to deliver genetic materials for various therapeutic purposes, but they need engineering solution to improve and control the delivery process. In Chapter 3, we demonstrate a highly efficient method for gene delivery into clinically relevant human cell types, such as induced pluripotent stem cells (iPSCs) and fibroblasts, reducing the protocol time by one full day. To preserve cell physiology during gene transfer, we designed a microfluidic strategy, which facilitates significant gene delivery in short transfection time (<1 minute) for several human cell types. This fast, optimized and generally applicable cell transfection method can be used for rapid screening of different delivery systems and has significant potential for high-throughput cell therapy applications. Microfluidic in vitro models are being developed to mimic individual or combination of various human organ functions for systematic studies, and for better predictive models for clinical studies. In Chapter 4, we outline a microfluidic-based culture system to study host-pathogen interaction in the human gut. We demonstrate that the infection of Enterohemorrhagic Escherichia coli (EHEC) in epithelial cells are oxygen dependent and can be used to prolong co-culture of bacterial and epithelial cells. This work presents a large scope to study the factors influencing the infection, especially the commensal microbiome in the human gut. Overall, this thesis shows how the microfluidic system can be useful in solving real-life problems and envision further advancements in the field of biotechnology.Item Design, Modeling, and Analysis of Microscale Pneumatic Valve Architectures to Simplify Integration of Small Displacement Actuators(2022-05) Hagstrom, NathanFluid power is an essential technology that underpins modern societal and industrial infrastructure. The performance of the majority of fluid power systems hinges on proper control valve function. Despite the importance, the core actuator technology used in control valves has remained largely unchanged for decades with incremental improvements made where possible. Now, conventional actuator technology development has reached a point of diminishing returns and provides a barrier to developing higher performance pneumatic systems. Use of smart materials in small displacement actuators, such as piezoelectric stack actuators, in control valves has the potential to break down barriers existing for conventional actuation methods. Piezoelectric stack actuators are useful as they have very low power consumption, nanometer displacement control resolution and microsecond response time. However, piezoelectric stack actuators are often overlooked due to inherent limitations in flow capacity created by their microscale actuator stroke. To enable revolutionary improvement in control valve design, this research answers fundamental questions required to enable widespread implementation of small displacement actuators, such as piezoelectric stacks, in proportional control valves. This research addresses limitations posed by existing pneumatic valve architectures through investigation of the potential for small displacement actuators use in applications where typically a relatively large displacement actuator would be needed. In so doing, this research investigates two methods for increasing flow capacity in valves using actuators with microscale stroke lengths. The first of two methods investigated uses a microfabricated array of micro-orifices to increase peripheral area acting as the governing flow restriction. The investigation involved design and characterization of a normally open axial proportional flow control valve using a piezostack actuator to modulate seal position. Further experimental and numerical study on the limitations posed when using an orifice array to increase flow area was summarily completed to develop an empirical basis for micro-orifice array design. The second of the two methods for increasing flow capacity was studied using experimental, numerical, and analytical methods. This method varied valve seal geometry to increase projected flow area and reduce viscous related flow losses. Results from study of the second method for increasing flow capacity enabled development of an analytical flow rate model to allow for model based valve design. Control valves better able to implement small displacement actuators, such as piezostack actuators, have potential to catalyze advances in numerous industries and applications. Impacted industries include: mobile robotics, medical instrumentation, natural gas handling, industrial control systems, and process control instrumentation. This research establishes a fundamental understanding of flow rate behavior in valves operating at microscale displacements. The valve architectures, empirical relationships, and flow models described provide a platform for future advances in control valve design and performance.Item Fabrication and characterization of micromachined dielectric thin fi lms and temperature sensors using thermoluminescence(2013-03) Kim, Sangho SamHigh-power laser technology has a number of applications, whether for the military (i.e., anti-missile weaponry) or for material processing, medical surgery, laser-induced nuclear fusion, and high-density data storage. However, external obstacles could cause a laser to problematically change its direction. Optical components such as mirrors already address this problem by deflecting a laser beam, but can be damaged easily due to the intensity of the laser. Therefore, this dissertation examines how to improve reliability of high power laser application systems by three signicant standards. First, we demonstrate that an atomic layer deposition (ALD) of Al2O3 can stabilize novel dielectric optical mirrors composed of SiO2 nanorods, whose porosity makes it attractive for use as a low refractive index material. Such a deposition can stabilize material properties in dry versus humid atmospheres, where both the refractive index and coefficient of thermal expansion (CTE) vary dramatically. This encapsulation ability is demonstrated in dielectric multilayers as a Distributed Bragg Reflector (DBR). Second, we show that the difference in hydroxyl signatures of micromachined dielectric membranes can make detection of optical materials' laser damage more accurate. This signature difference, appearing as the decrease in post-laser absorption peaks associated with hydroxyl groups (OH), is measured by Fourier transform infrared spectroscopy and corresponds to regions of high infuence from a Nd:YAG laser. This detection technique will be useful to determine the lifespan of the optical components used in a high power laser. Third, we found that heterogeneous thermoluminescent (TL) multilayers composed of LiF:Mg,Ti and CaF2:Dy with Kapton as an interlayer can enhance reconstruction of laser heating events through thermal gradients that penetrate deep into a material, thereby preserving memory of the temperature history of the surface. Using the finite-difference time-domain method (FDTD) and the first order kinetics model of TL, we estimate dynamic heat transfer and then populate the final luminescent intensity. A thermal contact conductance between the critical layers is also introduced to better simulate experimental results, thereby resolving dynamic temperatures by hundreds of milliseconds.Item MEMS Actuators for Tuning Nanometer-scale Airgaps in Heterostructures and Optical Instrumentation for Glacier Ice Studies(2016-01) Chan, Wing ShanMEMS Actuators for Tuning Nanometer-scale Airgaps in Heterostructures We developed a new actuator microstructure to control the spacing between closely spaced surfaces. Creating and controlling nanometer gaps is of interest in areas such as plasmonics and quantum electronics. For example, energy states in quantum well heterostructures can be tuned by adjusting the physical coupling distance between wells. Unfortunately, such an application calls for active control of a nano-scale air gap between surfaces which are orders of magnitude larger, which is difficult due to stiction forces. A vertical electrostatic wedge actuator was designed to control the air gap between two closely spaced quantum wells in a collapsed cantilever structure. A six-mask fab- rication process was developed and carried out on an InGaAs/InP quantum well het- erostructure on an InP substrate. Upon actuation, the gap spacing between the surfaces was tuned over a maximum range of 55 nm from contact with an applied voltage of 60 V. Challenges in designing and fabricating the device are discussed. Optical Instrumentation for Glacier Ice Studies We explored new optical instrumentation for glacier ice studies. Glacier ice, such as that of the Greenland and Antarctic ice sheets, is formed by the accumulation of snowfall over hundreds of thousands of years. Not all snowfalls are the same. Their isotopic compositions vary according to the planet’s climate at the time, and may contain part of the past atmosphere. The physical properties and chemical content of the ice are therefore proxies of Earth’s climate history. In this work, new optical methods and instrumentation based on light scattering and polarization were developed to more efficiently study glacier ice. Field deployments in Antarctica of said instrumentation and results acquired are presented.Item Optical micromachined ultrasound transducers (OMUT) : a new approach for high frequency ultrasound imaging(2014-11) Tadayon, Mohammad AminPiezoelectric technology is the backbone of most medical ultrasound imaging arrays, however, in scaling the technology to sizes required for high frequency operation (> 20 MHz), it encounters substantial difficulties in fabrication and signal transduction efficiency. These limitations particularly affect the design of intravascular ultrasound (IVUS) imaging probes whose operating frequency can approach 60 MHz. Optical technology has been proposed and investigated for several decades as an alternative approach for high frequency ultrasound transducers. However, to apply this promising technology in guiding clinical operations such as in interventional cardiology, brain surgery, and laparoscopic surgery further raise in the sensitivity is required. Here, in order to achieve the required sensitivity for an intravascular ultrasound imaging probe, we introduce design changes making use of alternative receiver mechanisms. First, we present an air cavity detector that makes use of a polymer membrane for increased mechanical deflection. We have also significantly raised the thin film detector sensitivity by improving its optical characteristics. This can be achieved by inducing a refractive index feature inside the Fabry-Perot resonator that simply creates a waveguide between the two mirrors. This approach eliminates the loss in energy due to diffraction in the cavity, and therefore the Q-factor is only limited by mirror loss and absorption. To demonstrate this optical improvements, a waveguide Fabry-Perot resonator has been fabricated consisting of two dielectric Bragg reflectors with a layer of photosensitive polymer between them. The measured finesse of the fabricated resonator was 692, and the Q-factor was 55000. The fabrication process of this device has been modified to fabricate an ultrasonically testable waveguide Fabry-Perot resonator. By applying this method, we have achieved a noise equivalent pressure of 178 Pa over a bandwidth of 28 MHz or 0.03 Pa/Hz1/2 which is approximately 20-fold better than a similar device without a waveguide. The finesse of the tested Fabry-Perot resonator was around 200. This result is 5 times higher than the finesse measured in the same device outside the waveguide region. In future, our developed technology can be integrated on the tip of an optical fiber bundle and applied for intravascular ultrasound imaging.