Digital microfluidics (DMF) has recently emerged as a popular technology for a wide range of applications. In DMF, nL-mL droplets containing samples and reagents are controlled(i.e., moved, merged, mixed, and dispensed from reservoirs) by applying a series of electrical potentials to an array of electrodes coated with a hydrophobic insulator. DMF is distinct from microchannel-based fluidics as it allows for precise control over multiple reagent phases (liquid and solid) in heterogeneous systems with no need for complex networks of microvalves. In this thesis, digital microfluidics has been applied to address key challenges in the fields of chemistry, biology and medicine. For applications in chemistry, the first two-plate digital microfluidic platform for synchronized chemical synthesis is reported. The new method, which was applied to synthesizing peptide macrocycles, is fast and amenable to automation, and is convenient for parallel scale fluid handling in a straightforward manner. For applications in biology, I present the first DMF-based method for extraction of proteins (via precipitation) in serum and cell lysate. The performance of the new method was comparable to that of conventional techniques, with the advantages of automation and reduced analysis time. The results suggest great potential for digital microfluidics for proteomic biomarker discovery. Furthermore, I integrated DMF with microchannels for in-line biological sample processing and separations. Finally, for applications in medicine, I developed the first microfluidic method for sample clean-up and extraction of estrogen from one-microliter droplets of breast tissue homogenates, blood, and serum. The new method is fast and automated, and features >1000x reduction in sample use relative to conventional techniques. This method has significant potential for applications in endocrinology and breast cancer risk reduction. In addition, I describe a new microfluidic system incorporating a digital microfluidic platform for on-chip blood spotting and processing, and a microchannel emitter for direct analysis by mass spectrometry. The new method is fast, robust, precise, and is capable of quantifying analytes associated with common congenital disorders such as homocystinuria, phenylketonuria, and tyrosinemia.

This thesis describes the assembly and integration procedures, methods and strategies used for the Generic Nanosatellite Bus (GNB) developed at the Space Flight Laboratory. The design of the interconnection medium routing will be presented and aspects of thermal testing such as thermal shock procedures and the satellite support structure design for the thermal vacuum testing. The compliance of the assembly, integration and testing requirements is demonstrated through validation and implementation. Step by step procedures are presented for GNB assembly, solar cell bonding and thermal tape application. The evolution of the integration design is described based on optimizing efforts and GNB design changes. Flexible circuits are presented as an alternative to the conventional harness for future missions. Finally, general assembly, integration and thermal testing recommendations are offered to add to the wealth of knowledge acquired by SFL in the proper design of nanosatellites.

An on-site simulation-based practice lab was conducted with 42 students enrolled in a blended distance practical nursing diploma program at the end of their first year of study, prior to their clinical placements. The six-hour practice lab involved an orientation, small group activities involving three obstetric-related scenarios using the moderate fidelity simulator Noelle®, and a debriefing activity. An evening social activity was also provided. The study used a mixed method research design involving both quantitative and qualitative methods. Data were collected using a demographic questionnaire, a 20-item pre-test/post-test knowledge quiz, and three National League for Nursing (NLN) instruments — the Simulation Design Scale, the Educational Practices in Simulation Scale, and the Learner Satisfaction and Self-Confidence in Learning Scale — as well as a pre- and post-lab administration of Rovai’s (2002b) Classroom Community Scale. The qualitative component of the study involved semi-structured interviews with 25 students, three lab facilitators, and five clinical placement instructors. Analysis of data collected before and after the simulation-based lab revealed a significant increase in knowledge and sense of community in the group as a whole. Analysis of the results of the NLN instruments indicated that the simulation-based practice lab was instructionally effective. Students were highly positive in their ratings of the design elements and implementation of the simulation-based practice lab, satisfied with the simulation-based learning activities, and confident in their ability to provide patient care. The qualitative analysis added a rich, descriptive understanding of how the simulation-based practice lab promoted instructional effectiveness (i.e., skills and knowledge, confidence, and learner satisfaction), preparation for clinical placement, and community cohesion. Thematic analysis of the interview data identified the following major themes: benefits to distance learners, nurse-patient interaction, theory to practice, positive experience, sense of community, and supportive learning (student interviews); benefits of simulation experience, facilitator role, and technology (facilitator interviews); and theory to practice, positive experience, and sense of community (clinical instructor interviews). This research supports the use of on-site simulation-based practice labs as a means to provide greater readiness for clinical practice and strengthen the sense of community among distance learners. / 2012-06

The recent breakthroughs in genomics and molecular diagnostics will not be reflected in health-care systems unless the biogenetic or other nucleic acid-based tests are transferred from the laboratory to clinical market. Developments in microfabrication techniques brought lab-on-a-chip (LOC) into being the best candidate for conducting sample preparation for such clinical devices, or point-of-care testing set-ups. Sample preparation procedure consists of several stages including cell transportation, separation, cell lysis and nucleic acid purification and detection. LOC, as a subset of Microelectromechanical systems (MEMS), refers to a tiny, compact, portable, automated and easy-to-use microchip capable of performing the sample-preparation stages together. Complexity in micro-fabrications and inconsistency of the stages oppose integration of them into one chip. Among the variety of mechanisms utilized in LOC for cell lysis, electrical methods have the highest potential to be integrated with other microchip-based mechanisms. There are, however, major limitations in electrical cell lysis methods: the difficulty and high-cost fabrication of microfluidic chips and the high voltage requirements for cell lysis. Addressing these limitations, the focus of this thesis is on realization of cell lysis microchips suitable for LOC applications. We have developed a new methodology of fabricating microfluidic chips with electrical functionality. Traditional lithography of microchannel with electrode, needed for making electro-microfluidic chips, is considerably complicated. We have combined several easy-to-implement techniques to realize electro-microchannel with laser-ablated polyimide. The current techniques for etching polyimide are by excimer lasers in bulky set-ups and with involvement of toxic gas. We present a method of ablating microfluidic channels in polyimide using a 30W CO2 laser. Although this technique has poorer resolution, this approach is more cost effective, safer and easier to handle. We have verified the performance of the fabricated electro-microfluidic chips on electroporation of mammalian cells. Electrical cell lysis mechanisms need an operational voltage that is relatively high compared to other cell manipulation techniques, especially for lysing bacteria. Microelectro-devices have dealt with this limitation mostly by reducing the inter-distance of electrodes. The technique has been realized in tiny flow-through microchips with built-in electrodes in a distance of a few micrometers which is in the scale of cell size. In addition to the low throughput of such devices, high probability of blocking cells in such tiny channels is a serious challenge. We have developed a cell lysis device featured with aligned carbon nanotube (CNT) to reduce the high voltage requirement and to improve the throughput. The vertically aligned CNT on an electrode inside a MEMS device provides highly strengthened electric field near the tip. The concept of strengthened electric field by means of CNT has been applied in field electron emission but not in cell lysis. The results show that the incorporation of CNT in lysing bacteria reduces the required operational voltage and improves throughput. This achievement is a significant progress toward integration of cell lysis in a low-voltage, high-throughput LOC. We further developed the proposed fabrication methodology of micro-electro-fluidic chips, described earlier, to perform electroporation of single mammalian cell. We have advanced the method of embedding CNT in microchannel so that on-chip fluorescent microscopy is also feasible. The results verify the enhancement of electroporation by incorporating CNT into electrical cell lysis. In addition, a novel methodology of making CNT-embedded microfluidic devices has been presented. The embedding methodology is an opening toward fabrication of a CNT-featured LOC for other applications.

Lactic acid bacteria (LAB) are of interest because of their potential to modulate immune responses. The effects of LAB range from regulation to stimulation of the immune system. It has been reported that LAB affect health via two main mechanisms: directly through physical interactions between LAB and cells of the immune system, and indirectly through the products of these bacteria. The studies presented in this thesis examine the direct and indirect effects of LAB on the immune system specifically on murine dendritic cells (DCs). Mouse DCs (in form of the DC2.4 cell line) were treated in vitro with a fraction of bovine milk fermented with Lactobacillus helveticus-2 (LH-2) or three synthetic peptides identified within the fermented milk fraction. Cell culture supernatants were analyzed for presence of tumor necrosis factor (TNF)-α and interleukin (IL)-6 to determine the effects of LAB on DC activation. The results of this study showed that the ability of the milk derived fraction and the synthetic peptides to induce DC activation and production of pro-inflammatory cytokines was limited, suggesting that these peptides may induce regulatory immune responses. A series of studies was performed in vitro to investigate the effects of six LAB species and strains, (LH-2), Lactobacillus acidophilus-5 (La-5), Lactobacillus acidophilus-115 (La-115), Lactobacillus acidophilus-116 (La-116), Lactobacillus acidophilus-14 (La-14), and Lactobacillus salivarius, on maturation and activation of DC2.4. Production of TNF-α, IL-6 and IL-10 by DCs was determined after treating cells with live LAB. The expression of DC maturation markers, CD80 and CD40, was also measured using flow cytometry after stimulation with LAB. In addition, the expression of toll-like receptors (TLRs) 2, 4 and 9 by DCs stimulated with LAB was measured. Our results revealed that LAB act differentially on pro-inflammatory and anti-inflammatory cytokine production and induction of co-stimulatory molecules by DCs. Specifically, L. salivarius was found to be the most effective LAB to induce pro-inflammatory cytokine production and expression of co-stimulatory molecules. Moreover, La-14, La-116 and La-5 induced moderate maturation and activation of DCs. On the other hand, LH-2 and La-115 are the least likely lactobacilli to induce DC response. In conclusion, various strains and species of LAB can differentially regulate DC activation and maturation, raising the possibility that these microbes can influence and steer immune responses of the host.

No description available.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

This thesis describes the assembly and integration procedures, methods and strategies used for the Generic Nanosatellite Bus (GNB) developed at the Space Flight Laboratory. The design of the interconnection medium routing will be presented and aspects of thermal testing such as thermal shock procedures and the satellite support structure design for the thermal vacuum testing. The compliance of the assembly, integration and testing requirements is demonstrated through validation and implementation. Step by step procedures are presented for GNB assembly, solar cell bonding and thermal tape application. The evolution of the integration design is described based on optimizing efforts and GNB design changes. Flexible circuits are presented as an alternative to the conventional harness for future missions. Finally, general assembly, integration and thermal testing recommendations are offered to add to the wealth of knowledge acquired by SFL in the proper design of nanosatellites.

Biological/biochemistry analyses traditionally require bulky instruments and a great amount of volume of biological/chemical agents, and many procedures have to be performed in certain locations such as medical centers or research institutions. These limitations usually include time delay in testing. The delays may be critical for some aspects such as disease prevention or patient treatment. One solution to this issue is the realization of point-of-care (POC) testings for patients, a domain in public health, meaning that health cares are provided near the sites of patients using well-designed and portable medical devices. Transportation of samples between local and central institutions can therefore be reduced, facilitating early and fast diagnosis. A closely related topic in engineering, lab-on-a-chip (LOC), has been discussed and practiced in recent years. LOC emphasizes integrating several functions of laboratory processes in a small portable device and performing analysis using only a very small amount of sample volume, to achieve low-cost and rapid analysis. From an engineer's point of view, LOC is the strategy to practice the idea of POC testing. This dissertation aimed at exploring the POC potentials of porous membrane-base LOC devices, which can be used to simplify traditional and standard laboratory procedures. In this study, three LOC prototypes are shown and discussed. First the protein sensor incorporating with silica nanofiber membrane, which has shown 32 times more improvement of sensitivity than a conventional technique and a much shorter detection time; secondly the bacteria filter chip that uses a sandwiched aluminum oxide membrane to stabilize the bacteria and monitor the efficacy of antibiotics, which has reduced the test time from 1 day of the traditional methods to 1 hour; the third is the sensor combining microfluidics and silica nanofiber membrane to realize Surface Enhanced Raman Spectroscopy on bio-molecules, which has enhancement factor 10^9 and detection limit down to nanomolar, but simple manufacturing procedures and reduced fabrication cost. These results show the porous-base membrane LOC devices may have potentials in improving and replacing traditional detection methods and eventually be used in POC applications.

CPAP is the most common treatment for moderate to severe sleep apnea in adults. Despite its efficacy, patients’ safety, comfort and compliance are issues to be considered and improved in CPAP design. The issues include condensation, carbon dioxide in inhaled air, humidity and temperature of inhaled air. When a CPAP user breaths deeply, there will be some air not fully expelled and may be driven back into the heated air delivery tube (HADT). An interest has existed in what impacts this so called reverse flow may bring about to the CPAP use. The main objectives of this research are to quantify the reverse flow and its influence on carbon dioxide re-breathing, delivered humidity to the patient and condensation in the HADT. Within this thesis, two computer models of the CPAP system have been constructed on Simulink™ in the Matlab™ environment. One is about the CPAP fluid dynamic performance and carbon dioxide re-breathing and the other is on thermodynamic performance. The models can predict the dynamic behaviour of the CPAP machine. They are able to mimic the breath induced airflow fluctuation, and flow direction changes over wide real working ranges of ambient conditions, settings and coefficients. These models can be used for future analysis, development, improvement and design of the machine. The fluid dynamic and thermodynamic models were experimentally validated and they have proved to be valuable tool in the work. The main conclusions drawn from this study are: • Reverse flow increases when breaths load increases and pressure setting decreases. • Reverse flow does not definitely add exhaled air to the next inhalation unless the reverse flow is relatively too much. • Mask capacity does not influence the reverse flow. • The exhaled air re-breathed is mainly due to that stays in the mask, therefore larger mask capacity increases the exhaled air re-breath and the percentage of exhaled air in next inhalation drops when the breath load increases. • Deep breathing does not significantly change the total evaporation in chamber. • When deep breathing induced reverse flow occurs, condensation occurs or worsens in the HADT near the mask. This happens only when the humidity of the airflow from the CPAP is much lower than that of the exhaled air and the tube wall temperature is low enough for condensation to occur. • The deep breathing and reverse flow do not significantly influence the average inhaled air temperature. • The overall specific humidity in inhaled air is lower under deep breathing. • Mask capacity does not influence the thermal conditions in the HADT and the inhaled air specific humidity. Also the mask capacity does not significantly influences the inhaled air temperature.