Most embryonic development and tissue self-assembly requires the integration of cell movements within multiple cell layers composed of different cell types, which are integrated with the signaling networks in these 3D environments. Although the role of cell mechanics in tissue self-assembly has been demonstrated, little is known about the mechanical responses of 3D multi-layer tissues to chemical cues. To investigate the collective movements within multilayered tissues, I developed a novel microfluidic technique capable of removing desired height or width of tissue from a composite tissue. I call this technique "3D tissue-etching" because it is analogous to techniques used in the microelectromechanics (MEMS) field where complex 3D structures are built by successively removing material from a monolithic solid through subtractive manufacturing. I used a custom-designed microfluidic control system to deliver a range of tissue etching reagents (detergents, chelators, proteases, etc.) to specific regions of multilayered tissues microsurgically isolated from embryos of the African Clawtoed frog, Xenopus laevis. Xenopus embryos and explanted tissues have long been used to elucidate signaling and other cellular processes during development and here provide an ideal model 3D tissue etching. Long exposure to a narrow etchant stream cuts completely through cell-cell layers to expose the substrate. By reducing the exposure time a single layer may be removed. By controlling the width of the etchant and the exposure time a broader swath of the surface layer may be removed. For more refined etching, after removal of a broad swath the resistance circuits can be switched and a second narrow stream can remove only a single narrow band within the swath exposed cells. I developed tissue-etching techniques that allow me to shape complex multi-layered embryonic tissues. The ability to control 3D stimulation and the form of multicellular tissues will provide extend the tools of tissue engineering to synthesize highly complex 3D integrated multicellular biosystems. Integration of tissue etching in my custom microfluidic system provides a "test-bed" where a range of hypotheses concerning the control and regulation of development and cell differentiation can be implemented and tested.

This dissertation presents enabling technologies to fabricate thermo-responsive polymer composite based Lab-on-a-Chip (LOC) devices. LOC devices, also known as micro-total-analytical systems (microTAS) or microfluidic devices can amalgamate miniaturized laboratory functions on a single chip. This significant size reduction decreases the amount of required fluid volumes down to nano or pico-liters. The main commercial application of LOC devices is the biomedical fields. However, these devices are anticipated to make a technological revolution similar to the way miniaturization changed computers. In fact, medical and chemical analyses are predicted to shift from room-sized laboratories to hand-held portable devices. This dissertation is divided into three technologies. First, a series of terpolymer systems were synthesized and characterized to fabricate crosslinked coatings for phototunable swelling and create chemically patterned regions in order to conjugate cationic markers, proteins, or nanoparticles to the terpolymer coating. Second, antifouling surfaces were fabricated using magnetic thermo-responsive hydrogel structures via soft lithography. The structures were remote control activated with the use of AC magnetic fields. Finally, in order for LOC devices to fulfill its promise of bringing a laboratory to a hand-held device, they will have to be integrated with CMOS technology. Packaging will play a crucial role in this process. The last section will focus on the importance of coefficient of thermal expansion (CTE) mismatch in multi-chip modules. For the first technology, multi-functionalized terpolymer systems have been developed comprising of three units: N-isopropylacrylamide (NIPAAm), a stimuli responsive monomer that swells and collapses in response to temperature; methacryloxybenzophenone (MaBP), a photo-crosslinkable monomer that is activated at λ = 365 nm; and phenacyl methacrylate (PHEm), a photolabile protected functional group that generates localized free carboxyl groups in response to deprotection at λ = 254 nm. The multifunctional terpolymers can be spin-casted to form thin films of well-defined thickness, photo-crosslinked by a long UV wavelength light (λ = 365 nm) to form distinct structural patterns, and subsequently photo-chemically modified by a short UV wavelength light (λ = 254 nm). The photocleavage reaction by UV irradiation allows the production of free carboxylic groups that can be used to conjugate cationic markers, proteins, or nanoparticles to the terpolymer coating. Furthermore, the free carboxyl groups can be used to locally tune the swelling characteristics and transition temperature of the coatings. For the second technology, when Fe3O4 magnetic nanoparticles are integrated into PNIPAAm based composite systems, their resultant hyperthermia behavior becomes an ideal mechanism for remote controlled actuation. In this work, nano Fe3O4 octopods were seeded in fabricated PNIPAAm hydrogel micro-actuators. When the magnetic hydrogel structures were exposed to a magnetic field strength of 63 kA/m at a frequency of 300 kHz, the hydrogel micro-beams underwent a buckling effect when the field was absent and an unbuckling effect when the field was present. The hydrogel micro-beams were fabricated at an approximate distance from one another developing micromanipulating surfaces that were remote control activated. The response time, heating efficiency, and magnetic behavior were thoroughly studied. Lastly, micron sized polystyrene beads were exposed to the antifouling surfaces and movement of the beads was observed as the magnetic hydrogel micro-beams underwent their physical changes. For the third technology, a major reason of device failure in multi-chip module assemblies is a CTE mismatch between the underfill encapsulant material and the integrated circuit chip. Some of the failure mechanisms of microelectronic packaging due to CTE mismatch include fractures, delamination, or cracks through the device. In this section, the CTE of a commercially available underfill material is greatly reduced by loading the polymer resin material with hollow glass beads, to realize an overall effective CTE of 6.6 ppm/°C. Furthermore, the newly developed composite material exhibited outstanding thermomechanical stability at high temperatures beyond 150°C by holding a 3X lower CTE and a higher glass transition temperature.

The spinning process of hollow fiber membranes was investigated with regards to two fundamental phenomena: flow (shear and elongation) and phase separation. Quantitative analysis of phase separation kinetics of binary (polymer/solvent) and ternary (polymer/solvent/volatile co-solvent) polymer solution was carried out with a newly developed microfluidic device. The device enables visualization of in situ phase separation and structure formation in controlled vapor and liquid environments. Results from these studies indicated that there was a weak correlation between phase separation kinetics and macroscopic defect (macrovoid) formation. In addition, the effect of shear and elongation on membrane morphology was tested by performing fiber extrusion through microfluidic channels. It was found that the membrane morphology is dominated by different factors depending on the rate of deformation. At high shear rates typical of spinning processes, shear was found to induce macrovoid formation through normal stresses, while elongation suppressed macroscopic defect formation. Furthermore, draw resonance, one of the key instabilities that can occur during fiber spinning, was investigated. It was found that draw resonance occurs at aggressive elongation condition, and could be suppressed by enhanced phase separation kinetics. These results can be used as guidelines for predicting hollow fiber membrane spinnability.

Microfluidics promises to re-shape the current health-care system by transferring diagnostic tools from central laboratories to close vicinity of the patient (point-of-care). One of the most important operational steps in any diagnostic platform is sample preparation, which is the main subject in this thesis. The goal of sample preparation is to isolate targets of interest from their surroundings. The work in this thesis is based on three ways to isolate bacteria:  immune-based isolation, selective cell lysis, size-based separation. The first sample-preparation approach uses antibodies against lipopolysaccharides (LPS), which are surface molecules found on all gram-negative bacteria. There are two characteristics that make this surface molecule interesting. First, it is highly abundant: one bacterium has approximately a million LPS molecules on its cell-wall. Second, the molecule has a conserved region within all gram-negative bacteria, so using one affinity molecule to isolate disease-causing gram-negative bacteria is an attractive option, particularly from the point of view of sample preparation. The main challenge, however, is antigen accessibility. To address this, we have developed a treatment protocol that improves the capturing efficiency. The strategy behind selective cell lysis takes advantage of the differences between the blood-cell membrane and the bacterial cell-wall. These fundamental differences make it possible to lyse (destroy) blood-cells selectively while keeping the target of interest, here the bacteria, intact and, what is more important alive. Viability plays an important role in determining antibiotic susceptibility. Difference in size is another well-used characteristic for sample- separation. Inertial microfluidics can focus size-dependent particle at high flow-rates. Thus, particles of 10 µm diameter were positioned in precise streamlines within a curved channel.  The focused particles can then be collected at defined outlets.  This approach was then used to isolate white blood cells, which account for approximately 1% of the whole blood.  In such a device particles of 2µm diameter (size of bacteria) would not be focused and thereby present at every outlet. To separate bacteria from blood elasto-inertial microfluidics was used. Here, e blood components are diverted to center of the channels while smaller bacteria remain in the side streams and can subsequently be separated. / <p>QC 20141212</p>

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<p>Integrated sensing systems are designed to address a variety of problems, including clinical diagnosis, water quality testing, and air quality testing. The growing prevalence of tropical diseases in the developing world, such as malaria, trypanosomiasis (sleeping sickness), and tuberculosis, provides a clear and present impetus for portable, low cost diagnostics both to improve treatment outcomes and to prevent the development of drug resistance in a population. The increasing scarcity of available clean, fresh water, especially noticeable in the developing world, also presents a motivation for low-cost water quality diagnostic tools to prevent exposure of people to contaminated water supplies and to monitor those water supplies to effectively mitigate their contamination. In the developed world, the impact of second-hand cigarette smoke is receiving increased attention, and measuring its effects on public health have become a priority. The `point-of-need' technologies required to address these sensing problems cannot achieve a widespread and effective level of use unless low-cost, small form-factor, portable sensing devices can be realized. Optical sensors based on low cost polymer materials have the potential to address the aforementioned `point-of-need' sensing problems by leveraging low-cost materials and fabrication processes. For portable clinical diagnostics and water quality testing in particular, on-chip sample preparation is a necessity. Electrowetting-on-dielectric (EWD) technology is an enabling technology for chip-scale sample preparation, due to its very low power consumption compared to other microfluidics technologies and the ability to move fluids without bulky external pumps. Potentially, these technologies could be combined into a cell phone sized portable sensing device.</p><p>Towards the goal of developing a portable diagnostic device using EWD microfluidics with an embedded polymer microresonator sensor, this thesis describes a viable fabrication process for the system and explores the design trade-offs of such a system. The main design challenges for this system are optimization of the sensor's limit-of-detection, minimization of the insertion loss of the optical system, and maintaining the ability to actuate droplets onto and off of the sensor embedded in the microfluidic system. The polymer microresonator sensor was designed to optimize the limit-of-detection (LOD) using SU-8 polymer as the bus waveguide and microresonator material and SiO2 as the substrate cladding material. The fabrication process and methodology were explored with test devices using a tunable laser system working around a wavelength of 1550 nm using glucose solutions as a refractive index standard. This sensor design was then utilized to embed the sensor and bus waveguides into an EWD top plate in order to minimize the impact of the sensor integration on microfluidic operations. Finally, the performance of the embedded sensor embedded was evaluated in the same manner and compared to the performance of the sensor without the microfluidic system.</p><p>The primary result of this research was the successful demonstration of a high performance polymer microresonator sensor embedded in the top plate of an electrowetting microfluidic device. The embedded sensor had the highest reported figure-of-merit for any microresonator integrated with electrowetting microfluidics. The embedded microresonator sensor was also the first fully-embedded microresonator in an EWD system. Because the sensor was embedded in the top plate, full functionality of the EWD system was maintained, including the ability to move droplets onto and off of the sensor and to address the sensor with single droplets. Furthermore, the highest figure-of-merit for an SU-8 microresonator sensor yet reported at a probe wavelength of 1550 nm was measured on a test device fabricated with the embedded sensor structure described herein. Optimization of the sensor sensitivity utilized recently developed waveguide sensor design theory, which accurately predicted the measured sensitivity of the sensors. Altogether, the results show that embedding of a microresonator sensor in an EWD microfluidics system is a viable approach to develop a portable diagnostic system with the high efficiency sample preparation capability provided by EWD microfluidics and the versatile sensing capability of the microresonator sensor.</p> / Dissertation

Research in lab-on-a-chip (LOC) technology involving microfluidics is a growing field aiming at the development of miniaturized biomedical systems with rich functionality. In order to design effective LOC microfluidic systems, the flow fields and the fluids inside LOC devices need to be carefully characterized. High-resolution magnetic resonance imaging (MRI) offers a powerful non-intrusive technology for this application. In this thesis, the design and implementation of a prototype for a desktop high-resolution MRI instrument, consisting of a magnet, gradient coils, gradient amplifiers, and radio frequency (RF) electronics, is presented. To reduce the size and cost of this MRI instrument, a permanent magnetic configuration with a magnetic flux density of 0.6 T is designed with off-the-shelf NdFeB permanent magnets. The coils of the triaxial gradient module are developed using a novel lithography technique. This gradient module is capable of generating gradient fields as high as 2.83 T/m with custom made current amplifiers. The radio frequency (RF) probe is integrated with the gradient module and is connected to the RF electronics which are made using off-the-shelf components. Pulse sequences and signal processing for acquiring static images and velocity profiles are described. The performance of this instrument in terms of static and dynamic image resolution are presented. As a preliminary test, the velocity profile of water flowing inside a small tube was measured with a nominal resolution of 40 μm. The instrument is designed for a static resolution of better than 30 μm and a velocity resolution better than 50 μm/s. Improvements to the current instrument in addition to theoretical limitations are also detailed.

In modern microprocessors, thermal management has become one of the main hurdles in continued performance enhancement. Cooling schemes utilizing single phase microfluidics have been investigated extensively for enhanced heat dissipation from microprocessors. However, two-phase fluidic cooling devices are becoming a promising approach, and are less understood. This study aims to examine two-phase flow and heat transfer within a pin-fin enhanced micro-gap. The pin-fin array covered an area of 1cm x 1cm and had a pin diameter, height and pitch of 150μm, 200μm and 225μm, respectively, (aspect ratio of 1.33). This study covers both uniformly and partially heated scenarios. The working fluid used was R245fa. The average heat transfer coefficient and high speed flow visualization results indicated a rapid transition to the annular flow regime with a strong dependence on heat flux. Also, unique, conically-shaped two-phase wakes were observed, demonstrating the lateral spreading capability of the pin-fin array geometry.

Aquesta tesi centra els seus esforços en l'àmbit de la microfluídica, un camp relativament recent dins de la Mecànica de Fluids, amb un futur prometedor i amb un ritme d'investigació intens en les seves diferents especialitzacions. En aquest sentit, la tesi presenta dos aportacions científiques principals. Primer, aporta una eina numèrica d'elaboració pròpia per realitzar simulacions de fluxos reactius en microcanals. Eina que s'aplica satisfactòriament a la identificació dels principals processos de transport involucrats en la oxidació parcial del metà per a produir gas de síntesi, i a l'estudi de l'efecte que tenen alguns paràmetres d'operació en aquest procés reactiu. Segon, estén el coneixement dels fluxos multifàsics en microunions en T, estudiant experimentalment fluxos de dues fases amb fluids principalment miscibles i en condicions supercrítiques, que son portats al seu equilibri vapor-líquid. Durant aquest estudi, a més, reporta un succés inesperat que presenta futurs reptes en l'aplicació d'aquest tipus de fluxos multifàsics. / The present thesis focuses on microfluidics, a relatively recent field of Fluid Mechanics with promising expectations and with an intense scientific interest on its different areas. In this regard, the thesis aims to provide two main scientific contributions. First, it presents an in-house numerical tool to carry out simulations of reactive flows within microchannels. The tool is successfully applied to the identification of the main transport phenomena involved on the partial oxidation of methane to produce synthesis gas, and to the analysis of the effect of several operating parameters on this reactive process. Second, it extends the knowledge on multiphase flows in microfluidic T-junctions with an experimental study of two-phase flows of mixtures of potentially miscible fluids, in supercritical conditions and in vapour-liquid equilibrium. In this study it is also reported an unexpected phenomenon, which brings new challenges to the application of these kind of multiphase flows.