Applications for lab-on-a-chip devices have been expanding rapidly in the last decade due to their lower required volume of sample, faster experiments, smaller tools, more control, and ease of parallelization compared to their macroscale counterparts. Moreover, lab-on-a-chip devices provide important capabilities, including isolating rare cells from body fluids, such as isolating circulating tumor cells from blood or peritoneal fluid, which are not feasible or at least extremely difficult with macroscale devices. Particles experience different forces (and/or torques) when they are suspended in a fluid in a microdevice. A dominant force is the drag force on the particle as it flows through the fluid.  External forces such as dielectrophoresis, the motion of a particle due to its polarization in the presence of a non-uniform electric field, may also be applied. For instance, well-specified mixing or separation of particles can be achieved by using the combination of drag and dielectrophoretic forces. Two major mechanisms for manipulating particles in a microdevice include control of forces applied to the particles, such as those due to electric and velocity fields, and the geometry of the device that affects the nature of these fields. The coupling between the geometry of the microdevices and applied fields makes the prediction of associated forces inside the microdevice challenging and increasingly difficult when the applied field is time-dependent. Understanding the interaction of external forces and particles and fluid is critical for engineering novel microsystems. Determining this interaction is even more complicated when dealing with bioparticles, especially cells, due to their complex intrinsic biological properties which influence their electrical and mechanical properties. Particles with non-spherical geometries further increase the complexity, making drag and other shape-dependent forces, such as dielectrophoretic force, less predictable and more complicated. In order to introduce more complexity to the system and maintain precise control over particle movement and fluid flow, it is essential to have a comprehensive understanding about the mechanics of particles-fluid interaction and the dynamics of the particle movement. Although microfluidics has been investigated extensively, unanswered questions about the effect of forces on the particle remain. Answering these questions will facilitate designing novel and more practical microdevices for medical, biological, and chemical applications Microfluidics devices were engineered for differentiation of subpopulations of cells based on their bioelectrical properties. These microdevices were utilized for separating prostate, leukemia, and three different stages of breast cancer cells from hematologic cells with concentrations as low as 1:106 with efficiency of >95%. The microfluidic platform was also utilized to isolate prostate cancer stem cells (CSCs) from normal cancer cells based on their electrical signature. Isolating these cells is the first step towards the development of cancer specific therapies. The signal parameters required to selectively isolate ovarian cancer cells at different cancer stages were also compared with peritoneal cells as the first step in developing an early diagnostic clinical system centered on cell biophysical properties. Moreover, the effect of non-toxic concentrations of two metabolites, with known anti-tumor and pro-tumor properties, on the intrinsic electrical properties of early and late stages of ovarian cancer cells was investigated. This work is the first to show that treatment with non-toxic doses of these metabolites correlate with changes in cells electrical properties. / Ph. D.

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In the process of blood analysis, for biomarker detection, blood plasma or serumis analyzed, while Red blood cells (RBCs) are usually considered waste. A recentstudy has found that cytokine concentrations in RBC lysate are on average 12-fold higher than in plasma. Microfluidic devices for the extraction of plasma fromwhole blood and containers of dried blood spots have already been developed.They o↵er a small tool size, low required sample volume, and low productioncost, which makes them suitable for point-of-care applications.In this thesis, an approach of isolating and lysing RBCs in a commercial bloodfilter using a microfluidic device was investigated. The design is based on a previouslydeveloped microfluidic device for plasma extraction. It was used for plasmaextraction, washing, and RBC lysing with RBC lysis bu↵er. The device’s functionalitywas examined, and the output lysate analyzed through measurements ofhemoglobin concentration, optical microscopy and an Elisa test of the cytokineIL-3.The results show that 48% of the devices were subject to one of two problems.One was slow filling of the capillary channel, and the other was the lysate beingvisibly clear. These problems were attributed to blood cells obstructing the filtersand increasing flow resistance. The device lysate viewed through an optical microscopewas shown to contain a significant amount of blood cells in some cases,suggesting that cells were passing through the filters. The mean lysis efficiency ofthe devices was determined to be 20%, which with the Elisa test results, suggeststhat there is low rates of mixing between the RBCs and the lysate within the filtermatrix. In conclusion, the tested method of isolating and lysing RBCs needs tobe improved in terms of reliability and efficiency. It was shown to work in someof the cases, and so shows promise for future development. / Röda blodkroppar (RB) ses vanligtvis som avfall vid blodmatningar av biomarköreri plasma eller serum. Men en ny studie har funnit att koncentrationerna av cytokiner i lyserade RB är i snitt 12 gånger högre än i plasma. Mikrofluidiska apparater som extraherar plasma från helblod har redan utvecklats. Deras fördelarär att de är små, använder små provvolymer och är billiga att producera. Detta gör dem lampliga for patientnara analyser, eller s.k. point-of-care-användning.I det här arbetet prövas en metod för att isolera och lysera RB i ett kommersiellt blodfilter, med hjälp av en mikrofluidisk apparat. Designen av apparaten är baserad på en mikrofluidisk apparat som utvecklats för plasmaextrahering. Den används för plasmaextraktion, tvätt och lysering med lyseringsbu↵ert. Appa-ratens funktionalitet undersöktes, och RB-lysatet analyserades med mätningar avhemoglobinvärden, ljusmikroskopi och en Elisa-mätning av cytokinet IL-3.Resultaten visar att 48 % av apparaterna hade något av två problem. Det ena problemet var att den kapillära kanalen fylldes långsamt, och det andra var att lysatet var till synes ofärgat. Dessa problem tillskrivs att blodceller blockerar filtren och ökar flödesmotståndet. I ljusmikroskop visade sig lysatet från apparaten i vissa fall innehålla stora mängder blodceller. Detta tyder på att celler passerat igenom filtret. Medelvärdet av lyseringse↵ektiviteten i apparaterna visades vara 20 %. Tillsammans med Elisa-resultaten tyder detta på att vätskan i filtret blandas i otillräcklig utsträckning. Sammanfattningsvis behöver metoden för att isolera och lysera RB förbättras gällande tillförlitlighet och e↵ektivitet. Den visadesig fungera i vissa fall och är därför lovande för framtida utveckling.

Combining the nematode Caenorhabditis elegans with novel microfluidic technology has produced a phenotypic movement assay that is at once rapid, sensitive, and low-cost. The method is based on the neurophysiologic phenomenon of worms exhibiting robust, continuous, directed locomotion in response to mild electric fields inside a microchannel. As we demonstrate with the studies reported herein, our microfluidic electrotaxis platform is a unique tool for studying the effects of environmental and genetic manipulations on C. elegans’ movement behaviour, which in turn indicates the state of the organism’s neuronal and muscular systems. In one initiative to develop an inexpensive biosensor, we use the setup to measure the response of worms to common environmental pollutants. Results indicate that worms’ electrotactic swimming behaviour is particularly susceptible to metal salts. A comparison with traditional assays measuring fecundity, growth, and lifespan reveals that electrotactic speed shows a comparable level of sensitivity as a toxicity endpoint. Another study demonstrates that worms expressing a mutant form of α-synuclein, a familial Parkinson’s disease-related protein, show deficits in electrotactic swimming speed that coincide with dopaminergic neuron damage. We further show that both the electrotaxis and neuronal phenotypes can be ameliorated by treatment with curcumin, a putative neuroprotective agent. We have also used the platform to investigate the effects of other environmental and genetic stresses on electrotactic behaviour. Our findings indicate that the response can withstand many different insults but is affected by stresses that induce the mitochondrial and ER unfolded protein responses, which themselves play roles in preserving electrotactic swimming behaviour alongside the heat shock response. These data expand our knowledge of how the motor output component of C. elegans’ electrotactic response is perturbed by environmental and genetic manipulations, and also support the utility of microfluidic electrotaxis as a functional output of nematode locomotory circuits in a multitude of contexts. / Thesis / Doctor of Science (PhD)

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No description available.

Contraction flow of viscoelastic fluids has been a benchmark problem in non-Newtonian fluid mechanics because it mimics flows occurring in a number of industrial applications. It is also of considerable interest to academia to gain fundamental understanding of factors that affect the evolution of vortices and a complete understanding of the dynamics for a simple polymeric fluid has not been achieved. In this two part study we investigate the effect of pre deformation of a Boger fluid in a contraction geometry and the flow of surfactants in a parallel contraction geometry. Entry flow of a polymeric fluid results in the formation of upstream vortices,the presence of recirculation zones may lead to a nonuniform residence time and hence inferior quality products. In this work we study the effect of pre-stretching dilute flexible chain polymers by placing a cylinder in front of a contraction in a microfluidic device.This deformation applied to the polymer is remembered before it completely relaxes, this memory effect changes the rheological properties during the fading period of the deformation history. Applying pre-deformation gives rise to new type of vortex evolution that is different from the standard contraction case. Semi-dilute surfactant solutions that exhibit shear thickening nature can be potentially used in enhanced oil recovery to increase the sweep efficiency. Two parallel microfluidic contractions of different cross sectional area are used to investigate the rheological effect on the mass flux of the two channels. Shear thickening micellar solutions were found to increase the mass flux through the small channel compared to a newtonian fluid. This effect was observed only for a small range of flow rates. As flow rates increased inlet instabilities were observed that evolved into a chaotic behavior upon further increase in the net flow rate.

Polymer flooding is one of the most used chemical methods for enhanced oil recovery(EOR). However, laboratory studies and field applications of polymer injections often encounter polymer-induced clogging due to polymer transport and entrapment, leading to permeability reduction and diminished recovery performance. In this work, we focus on understanding polymer flow behavior using microfluidics devices and fluorescence microscopy. Microfluidic devices were designed to mimic and replicate the pore-network structures of oil-bearing conventional reservoir rocks. We present various flow experiments to study polymer transport and the underlying mechanisms of polymer retention in porous media. We assess the polymer-induced clogging of partially hydrolyzed polyacrylamides - HPAMs, using tracers. Afterward, we use a commercially available fluorescent polymer with microfluidics and single-molecule microscopy to give insights into individual molecule dynamics. Furthermore, we perform numerical simulations to replicate and extend the experimental work. As these experiments were conducted using commercially fluorescent polymer of low molecular weight and due to limitations of tracers to track polymers, we extended this work to investigate the transport of HPAMs, which is the most used polymer for EOR, at molecule-scale. However, existent methods in the literature are not suitable for fluorescently labeling ultra-high molecule weight polymers. Therefore, we present a novel method for synthesis of dye-labeled polymers that successfully tagged the HPAMS. Finally, we assessed the conformation and flow dynamics of the fluorescently labeled HPAM molecules. The findings highlight a limitation in some polymer screening workflows in the industry that suggest selecting the candidate polymers based solely on their molecular size and the size distribution of the rock pore-throats. Moreover, we present, for the first time, direct visualization of the three main mechanisms underlying polymer retention in porous media. We bring the first molecular evidence of polymer pore-clogging and permeability reduction reversibility, which sheds light on the controversy in the literature. In addition, we propose a new method for fluorescent labeling water-soluble ultra-high molecular weight polyacrylamides-based polymers that preserves their viscosifying properties. The method can be extended to any polymers containing carboxyl groups or groups that can be functionalized into carboxyls, and therefore, the applicability covers any fields that employ polymers.

A numerical simulation of electrowetting on a dielectric was performed in COMSOL to grant insight on various parameters that play a critical role in system performance. The specific system being simulated was the Open Drop experiment and the parameters being investigated were the applied voltage, contact angle at the advancing triple point, and droplet overlap onto neighboring actuated electrodes. These parameters were investigated with respect to their effect on droplet locomotion performance. This performance was quantified by the droplets velocity and the dielectrophortic (DEP) force’s magnitude; the DEP force was calculated from integration of the Maxwell Stress Tensor, however, the force was not integrated into the simulation to assist with droplet movement. It was found that as the droplet overlap onto the neighboring electrode, or droplet radius to electrode size ratio, decreased, the droplet velocity increased. As the applied potential increased, and induced contact angle at the advancing triple point decreased, droplet velocity also increased. Both the decreasing overlap and increasing voltage had a linear effect on droplet velocity. As the droplet overlap increased, the rate of change of droplet velocity decreased as increasing voltages were considered. A 2D DEP calculation illustrated that an increase in voltage induced a tenfold increase in the corresponding DEP force; a linear relationship was found between droplet overlap and DEP force for the Open Drop size regime.

In this thesis, the successful fabrication of 3D-printed microfluidic devices will be discussed. Fabrication is performed with a low-cost commercially available stereolithographic 3D printer utilizing a custom PEGDA resin formulation tailored for low non-specific protein adsorption based on my colleagues' work [Rogers et al., Anal. Chem. 83, 6418 (2011)]. Horizontal microfluidic channels with designed rectangular cross sectional dimensions as small as 300 um wide and 150 um tall are printed with 100% yield, as are cylindrical vertical microfluidic channels with 300 um designed (334 um actual) diameters. Moreover, two different resins developed by our group are utilized in the process of 3D-printing which is the novel aspect about this thesis since other groups have not done research on this aspect of 3D-printing.