Ma thèse comporte deux grandes parties, la première en biophysique et la seconde en science de l’éducation. La première partie présente des travaux à la frontière entre neurobiologie et microfluidique. Le but de ces travaux est de pouvoir reconstruire et étudier des réseaux complexes de neurones in vitro avec une topologie de connections synaptiques bien contrôlées. Une série de micro-structures mécanique et/ou chimique ont été étudiées pour leur capacité à (i) positionner les corps cellulaires des neurones, (ii) orienter la pousse des neurites, et (iii) différencier les axones des dendrites. Un premier réseau comportant trois populations de neurones connectées en série a été reconstruit à l’intérieur d’un circuit microfluidique. Ce réseau qui mime la voie perforante de l’hippocampe pourra être exploité pour des études en physiologie ou en neuro-dégénerescence. Une méthode entièrement optique de stimulation et d’observation de l’activité neuronal a été mise au point. Elle ouvre de nouvelles portes pour étudier des processus cognitifs complexes dans des systèmes simplifiés in vitro. La seconde partie de mon travail a permis le développement et l’étude de jeux pédagogiques pour l’apprentissage de la chimie en licence. Ces jeux, qui peuvent selon les cas remplacer un cours ou une séance d’exercices, donnent des résultats prometteurs pour l’aide à la compréhension et à la mémorisation de concepts tels que la géométrie des molécules ou la réactivité entre molécules organiques. / My PhD is divided in two parts one on biophysic of neuronal networks and one on science of education. The first part present results at the frontier between neurobiology and microfluidic. The overarching goal of this work was to develop tools and methods to build and study complex neuronal networks controlling the topology of synaptic connexions. Micro-patterning techniques with mechanical and/or chemical constraints were explored regarding their capacity to (i) position cell bodies, (ii) orient neurite outgrowth and (iii) polarize neurons. For the first time, a network comprising three different neuronal populations connected in specified directions was reconstructed in a microfluidic device. This network that mimics the perforant pathway of the hippocampus can be used to study physiological rythms or neurodegenerative processes including Alzheimer’s disease. A novel and fully optical method is presented to stimulate and record neuronal activity in vitro. It opens new routes to study complex cognitive processes in simplified in vitro systems. The second part of my work present the development and assessment of educational games in chemistry at the undergraduate level. These games that can either be used to replace courses or exercises, seem promising to improve the understanding and memorization of chemistry concepts og geometries of molecules and organic reactivity.

Thanks to their capability of transmitting light with low loss, optical fibers have found a wide range of applications in illumination, imaging, and telecommunication. However, since the light guided in a regular optical fiber is well confined in the core and effectively isolated from the environment, the fiber does not allow the interactions between the light and matters around it, which are critical for many sensing and actuation applications. Specially shaped optical fibers endow the guided light in optical fibers with the capability of interacting with the environment by modifying part of the fiber into a special shape, while still preserving the regular fiber’s benefit of low-loss light delivering. However, the existing specially shaped fibers have the following limitations: 1) limited light coupling efficiency between the regular optical fiber and the specially shaped optical fiber, 2) lack special shape designs that can facilitate the light-matter interactions, 3) inadequate material selections for different applications, 4) the existing fabrication setups for the specially shaped fibers have poor accessibility, repeatability, and controllability. The overall goal of this dissertation is to further the fundamental understanding of specially shaped fibers and to develop novel specially shaped fibers for different applications. In addition, the final part of this dissertation work proposed a microfluidic platform that can potentially improve the light-matter interactions of the specially shaped fibers in fluidic environments. The contributions of this dissertation work are summarized as follows: 1) An enhanced fiber tapering system for highly repeatable adiabatic tapered fiber fabrications. An enhanced fiber tapering system based on a novel heat source and an innovative monitoring method have been developed. The novel heat source is a low-cost ceramic housed electric furnace (CHEF). The innovative monitoring method is based on the frequency-domain optical transmission signal from the fiber that is being tapered. The enhanced fiber tapering system can allow highly repeatable fabrication of adiabatically tapered fibers. 2) A lossy mode resonance (LMR) sensor enabled by SnO2 coating on a novel specially shaped fiber design has been developed. The developed LMR sensor has a D-shape fiber tip with SnO2 coating. It has the capability of relative humidity and moisture sensing. The fiber-tip form factor can allow the sensor to be used like a probe and be inserted into/removed from a tight space. 3) Specially shaped tapered fibers with novel designs have been developed for integrated photonic and microfluidic applications. Two novel specially tapered fibers, the tapered fiber loop and the tapered fiber helix have been developed. The tapered fiber loop developed in this work has two superiority that differentiated itself from previous works: a) the mechanical stability of the tapered fiber loop in this work is significantly better. b) the tapered fiber loops in this work can achieve a diameter as small as 15 ?m while still have a high intrinsic optical quality factor of 32,500. The tapered fiber helix developed in this work has a 3D structure that allows it to efficiently deliver light to locations out of the plane defined by its two regular fiber arms. Applications of the tapered fiber helices in both integrated photonic device characterizations and microparticle manipulations have been demonstrated. 4) Developed an acrylic-tape hybrid microfluidic platform that can allow function reconfiguration and optical fiber integration. A low-cost, versatile microfluidic platform based on reconfigurable acrylic-tape hybrid microfluidic devices has been developed. To the best of the author’s knowledge, this is the first time that the fabrication method of sealing the acrylic channel with a reconfigurable functional tape has been demonstrated. The tape-sealing method is compatible with specially shaped fiber integrations.

DuMPLING is a newly developed high-throughput method to study singlecellphenotypes in a pooled and barcoded library using a microfluidicchip. The chip enables parallel biophysical measurements of singlecells, after which in-situ genotyping connects the cells to a certainstrain of the library. The method has been previously applied with abarcoded library, where genotyping was performed on barcodes presenton high copy number plasmids. In this project, I apply and developthe Rolling Circle Amplification method to amplify the signal frombarcodes present on the E. coli chromosome. A small librarycontaining three different chromosomal barcodes is investigated. Veryhigh efficiency of signal generation is achieved for the firstbarcode, good efficiency is achieved for the second, and no signal isachieved for the third. Genotyping is also successfully performed ona strain with two different barcodes present on the chromosome. Thegenotyping method described herein can be applied to screen foradditional barcodes that may be incorporated in a larger library thatin turn can be used to ask important biological questions, forexample using the high throughput DuMPLING method.

This master thesis deals with the use of microfluidics for the purpose of microfluidic enzymatic reactor for drug screening. At first it considers the issue from a theoretical point of view – describes microfluidics as a newly developing and promising field of production of microfluidic devices, materials, biomedical applications and advantages and disadvantages of microfluidics overall. Furthermore, it focuses on an area of analytical utilization of enzymes within enzyme reactors. In the first part of the experimental section, conditions for the testing of enzymes of xenobiotics metabolism in the liver were optimized, namely the model of coumarin metabolism via the spectrofluorimetry method. The second part of the experimental work dealt with optimization of the fabrication conditions of microfluidic chips from OSTE (off-stoichiometry Thiol Ene) via the soft lithography method. Subsequently, the functionality of the produced chips was tested. Based on the results of both parts of the experimental work, an evaluation was carried out to assess the suitability of their interconnection for future research – screening of microsomal enzyme activity and model biotransformation of drugs within the channels of the fabricated devices.

Cette thèse porte sur la mise en place et le développement d’une approche expérimentale pour l’étude de la dynamique spatio-temporelle de réseaux de réactions à base d’ADN. Nos résultats démontrent la capacité des réseaux d’ADN à se spatialiser sous la forme d’ondes progressives. Nous avons également pu obtenir des motifs stationnaires à base d’ADN et d’assemblages de billes. Ce travail contribue donc à la conception de motifs spatio-temporels de réactions chimiques et de matériaux par le biais de réseaux réactionnels biochimiques programmables. Nous apportons également de nouvelles données sur l’émergence d’ordre spatio-temporel à partir de processus de réaction-diffusion. De ce fait, cette étude contribue à une meilleure compréhension des principes fondamentaux qui régissent l’apparition d’une auto-organisation moléculaire dans un système chimique hors-équilibre. De plus, la combinaison de réseaux synthétiques d’ADN, du contrôle du coefficient de diffusion de plusieurs espèces d’ADN et de la micro-fluidique peut donner lieu à des motifs spatiaux stables, comme par exemple, les fameuses structures de Turing, ce qui tend à confirmer le rôle de celles-ci dans la morphogénèse. / This PhD work is devoted to developing an experimental framework to investigate chemical spatiotemporal organization through mechanisms that could be at play during pattern formation in development. We introduce new tools to increase the versatility of DNA-based networks as pattern-forming systems. The emergence of organization in living systems is a longstanding fundamental question in biology. The two most influential ideas in developmental biology used to explain chemical pattern formation are Wolpert's positional information and Turing's reaction-diffusion self-organization. In the case of positional information, the pattern emerges from a pre-existing morphogen gradient across space that provides positional values as in a coordinate system. Whereas, the Turing mechanism relies on self-organization by driving a system of an initially homogeneous distribution of chemicals into an inhomogeneous pattern of concentration by a process that involves solely reaction and diffusion. Although numerical simulations and mathematical analysis corroborate the incredible potential of reaction-diffusion mechanisms to generate patterns, their experimental implementation is not trivial. And despite of the exceptional achievements in pattern formation with Belousov–Zhabotinsky systems, these are difficult to engineer, thus limiting their experimental implementation to few available mechanisms. In order to engineer reaction-diffusion systems that display spatiotemporal dynamics the following three key elements must be controlled: (i) the topology of the network (how reactions are linked to each other, i.e. in a positive or negative feedback manner), (ii) the reaction rates and (iii) the diffusion coefficients. Recently, using nucleic acids as a substrate to make programmable dynamic chemical systems together with the lessons from synthetic biology and DNA nanotechnology has appeared as an attractive approach due to the simplicity to control reaction rates and network topology by the sequence. Our experimental framework is based on the PEN-DNA toolbox, which involves DNA hybridization and enzymatic reactions that can be maintained out of equilibrium in a closed system for long periods of time. The programmability and biocompatibility of the PEN-DNA toolbox open new perspectives for the engineering of the reaction-diffusion chemical synthesis, in particular in two directions. Firstly, to study biologically-inspired pattern-forming mechanisms in simplified, yet relevant, experimental conditions. Secondly to build new materials that would self-build by a process inspired from embryo morphogenesis. We worked towards the goal of meeting the two requirements of Turing patterning, transferring chemical spatiotemporal behavior into material patterns, and imposing boundary conditions to spatiotemporal patterns. Therefore, the structure of this document is divided into four specific objectives resulting in four chapters. In chapter 1 we worked on testing a DNA-based reaction network with an inhibitor-activator topology. In chapter 2 we focused on developing a strategy to tune the diffusion coefficient of activator DNA strands. In chapter 3 we explored how chemical patterns determine the shape of a material. Finally, in chapter 4 we addressed the issue of controlling the geometry over a DNA-based reaction-diffusion system. Overall, we have expanded the number of available tools to study chemical and material pattern formation and advance towards Turing patterns with DNA.

<div> <div> <div> <p>Microfluidics is a new and emerging field that has applications in a myriad of microfluidic industrial applications such as biochemical engineering, analytical processing, biomedical engineering and separation of cells. Microfluidics operations are carried out in microfluidic chips, and the traditional method of fabrication is carried out in a cleanroom. However, this fabrication method is very costly and also requires professional trained personnel. In this thesis, a low-cost fabrication platform was developed based on soft-lithography technique developed to fabricate the microfluidic devices with resolution at microscale. This fabrication method is advantageous and novel because it is able to achieve the microscale fabrication capability with simple steps and lower-level laboratory configuration. In the developed fabrication platform, an array of ultraviolet light was illuminated onto a photoresist film that has a negative photomask with a microfluidic design on it. The photoresist film is then developed, and a silicon polymer of polydimethylsiloxane (PDMS) is chosen to be the material for the device. In this work, the performance and resolution of the fabrication system was evaluated using scanning electron microscopy (SEM), polymer resolution test and light intensity analysis. </p> <p>Based on the success of the development of microfluidics fabrication platform, various experiment of mixing and separation was conducted and studied because the utilization of the microfluidic device for mixing and separation is very valuable in biomedical and chemical engineering. Although there are a lot of applications reported, the precise separation and mixing at microscale still meet some difficulties. Mixing in micromixers is extremely time-consuming and requires very long microchannels due to laminar flow and low Reynolds number. Particle separation is also hard to be achieved because the size of micron bioparticles is very small and thus the force is not strong enough to manipulate their motion. The integration of magnetic field is an active method to strengthen both mixing and separation that has been widely applied in the biomedical industry overcome these difficulties because of its compatibility with organic particles. However, most magnetic mixing and separation use bulky permanent magnets that leave a large footprint or electromagnets that generate harmful Joule heat to organic and bio-particles. In this work, microscale magnet made of a mixture of neodymium powder and polydimethylsiloxane was developed and integrated into microfluidic system to achieve both rapid mixing of ferrofluids and separation of microparticles. Systematic experiments were conducted to discuss the effect of various parameters on the performance of magnetic mixing and separation of microparticles. It was found that channel geometry, flow filed, and magnetic properties will affect the transport phenomena of ferrofluid and microparticles, and thus mixing and separation efficiency. These findings are of great significance for the high throughput sorting of cancer cells and its mixing between drug for therapy treatment.</p></div></div></div>

Cette thèse vise à contribuer à la caractérisation, à l’aide de modélisation et d’expérience, de la dynamique de bulle en microfluidique. Deux régimes d’écoulements rencontrés en microfluidique sont étudiés, le régime bubbly flow et le régime Taylor flow. En particulier, la première partie de cette thèse traite de la dynamique d’un écoulement de type bubbly flow dans un microcanal rectiligne de section circulaire en présence de surfactants. Le code de calcul numérique JADIM est utilisé. Une méthode numérique permettant, d’une part, de simuler le transport de surfactants le long d’une interface qui bouge et qui se déforme, et d’autre part, de simuler l’effet Marangoni crée par une distribution inhomogène de ces surfactants sur cette interface, est implémentée et validée. Les simulations effectuées avec ce code concernant la dynamique d’un écoulement de type bubbly flow montrent par exemple que, le confinement créé par les parois du microcanal résulte en une distribution des surfactants sur la surface des bulles qui est fondamentalement différente d’une distribution rencontrée dans le cas d’une bulle qui se déplace dans un liquide de dimension infinie. En effet, les surfactants s’accumulent en des locations spécifiques sur la surface des bulles et créent des forces de Marangoni locale, qui influencent drastiquement la dynamique des bulles. Dans certains cas, les surfactants peuvent même engendrer une désintégration de la bulle, un mécanisme qui est rationalisé par un bilan de force à l’arrière de la bulle. La méthode numérique implémentée dans cette thèse est également utilisée pour un problème pratique concernant la production artisanale de Mezcal, une boisson alcoolisée produite au Méxique. La seconde partie de cette thèse traite de la dynamique d’un écoulement de type Taylor flow, à l’aide d’expérience et de modélisation. Une méthode expérimentale permettant de mesurer l’épaisseur du film de lubrification qui se forme entre une bulle de Taylor et les parois du microcanal est développée. Cette méthode requiert uniquement une image « brightfield » de la bulle. En plus de la mesure de l'epaisseur du film de lubrification, la méthode permet aussi de mesurer la profondeur du microcannal. Enfin, l'utilisation de la méthode proposée couplée à la mesure de la vitesse de translation de la bulle permet de déduire la tension de surface de celle-ci. Dans le dernier chapitre de cette thèse, l'influence des effets gravitaires sur la dynamique des écoulements de Taylor est quantifiée. Quoique souvent négligée en microfluidique, il est montré que les effets gravitaires peuvent avoir un impact significatif sur la dynamique des écoulements de Taylor. Ces impacts sont quantifiés à l'aide d'expériences et de modélisations. Ce travail a été réalisé à la Princeton University avec Professeur Howard A. Stone pendant un séjour de 7 mois. / This thesis aims at contributing to the characterization of the dynamics of bubbles in microfluidics through modeling and experiments. Two flow regimes encountered in microfluidics are studied, namely, the bubbly flow regime and the Taylor flow regime (or slug flow). In particular, the first part of this thesis focuses on the dynamics of a bubbly flow inside a horizontal, cylindrical microchannel in the presence of surfactants using numerical simulations. A numerical method allowing to simulate the transport of surfactants along a moving and deforming interface and the Marangoni stresses created by an inhomogeneous distribution of these surfactants on this interface is implemented in the Level set module of the research code. The simulations performed with this code regarding the dynamics of a bubbly flow give insights into the complexity of the coupling of the different phenomena controlling the dynamics of the studied system. Fo example it shows that the confinement imposed by the microchannel walls results in a significantly different distribution of surfactants on the bubble surface, when compared to a bubble rising in a liquid of infinite extent. Indeed, surfactants accumulate on specific locations on the bubble surface, and create local Marangoni stresses, that drastically influence the dynamics of the bubble. In some cases, the presence of surfactants can even cause the bubble to burst, a mechanism that is rationalized through a normal stress balance at the back of the bubble. The numerical method implemented in this thesis is also used for a practical problem, regarding the artisanal production of Mezcal, an alcoholic beverage from Mexico. The second part of the thesis deals with the dynamics of a Taylor flow regime, through experiments and analytical modeling. An experimental technique that allows to measure the thickness of the lubrication film forming between a pancake-like bubble and the microchannel wall is developed. The method requires only a single instantaneous bright-field image of a pancake-like bubble translating inside a microchannel. In addition to measuring the thickness of the lubrication film, the method also allows to measure the depth of a microchannel. Using the proposed method together with the measurment of the bubble velocity allows to infer the surface tension of the interface between the liquid and the gas. In the last chapter of this thesis, the effect of buoyancy on the dynamics of a Taylor flow is quantified. Though often neglected in microfluidics, it is shown that buoyancy effects can have a significant impact on the thickness of the lubrication film and consequently on the dynamics of the Taylor flow. These effects are quantified using experiments and analytical modeling. This work was performed at Princeton University with Professor Howard A. Stone during a seven month stay.

Thanks to their capability of transmitting light with low loss, optical fibers have found a wide range of applications in illumination, imaging, and telecommunication. However, since the light guided in a regular optical fiber is well confined in the core and effectively isolated from the environment, the fiber does not allow the interactions between the light and matters around it, which are critical for many sensing and actuation applications. Specially shaped optical fibers endow the guided light in optical fibers with the capability of interacting with the environment by modifying part of the fiber into a special shape, while still preserving the regular fiber’s benefit of low-loss light delivering. However, the existing specially shaped fibers have the following limitations: 1) limited light coupling efficiency between the regular optical fiber and the specially shaped optical fiber, 2) lack special shape designs that can facilitate the light-matter interactions, 3) inadequate material selections for different applications, 4) the existing fabrication setups for the specially shaped fibers have poor accessibility, repeatability, and controllability. The overall goal of this dissertation is to further the fundamental understanding of specially shaped fibers and to develop novel specially shaped fibers for different applications. In addition, the final part of this dissertation work proposed a microfluidic platform that can potentially improve the light-matter interactions of the specially shaped fibers in fluidic environments. The contributions of this dissertation work are summarized as follows: 1) An enhanced fiber tapering system for highly repeatable adiabatic tapered fiber fabrications. An enhanced fiber tapering system based on a novel heat source and an innovative monitoring method have been developed. The novel heat source is a low-cost ceramic housed electric furnace (CHEF). The innovative monitoring method is based on the frequency-domain optical transmission signal from the fiber that is being tapered. The enhanced fiber tapering system can allow highly repeatable fabrication of adiabatically tapered fibers. 2) A lossy mode resonance (LMR) sensor enabled by SnO2 coating on a novel specially shaped fiber design has been developed. The developed LMR sensor has a D-shape fiber tip with SnO2 coating. It has the capability of relative humidity and moisture sensing. The fiber-tip form factor can allow the sensor to be used like a probe and be inserted into/removed from a tight space. 3) Specially shaped tapered fibers with novel designs have been developed for integrated photonic and microfluidic applications. Two novel specially tapered fibers, the tapered fiber loop and the tapered fiber helix have been developed. The tapered fiber loop developed in this work has two superiority that differentiated itself from previous works: a) the mechanical stability of the tapered fiber loop in this work is significantly better. b) the tapered fiber loops in this work can achieve a diameter as small as 15 ?m while still have a high intrinsic optical quality factor of 32,500. The tapered fiber helix developed in this work has a 3D structure that allows it to efficiently deliver light to locations out of the plane defined by its two regular fiber arms. Applications of the tapered fiber helices in both integrated photonic device characterizations and microparticle manipulations have been demonstrated. 4) Developed an acrylic-tape hybrid microfluidic platform that can allow function reconfiguration and optical fiber integration. A low-cost, versatile microfluidic platform based on reconfigurable acrylic-tape hybrid microfluidic devices has been developed. To the best of the author’s knowledge, this is the first time that the fabrication method of sealing the acrylic channel with a reconfigurable functional tape has been demonstrated. The tape-sealing method is compatible with specially shaped fiber integrations.

<div>Studying the motion of cells and investigating their migration patterns in inertial microchannels have been of great interest among researchers because of their numerous biological applications such as sorting, separating, and filtering them. A great drawback in conventional microfluidics is the inability to focus extremely small biological particles and pathogens in the order of sub-micron and nanometers due to the requirement of designing an impractically elongated microchannel, which could be in the order of a few meters in extreme cases. This restriction is because of the inverse correlation between the cube of the particle size and the theoretically required channel length. Exploiting an oscillatory flow is one solution to this issue where the total distance that the particle needs to travel to focus is virtually extended beyond the physical length of the device. Due to the present symmetry in such flow, the directions of the lift forces acting on the particle remain the same, making the particle focusing feasible. </div><div><br></div><div>Here, we present results of simulation of such oscillatory flows of a single capsule in a rectangular microchannel containing a Newtonian fluid. A 3D front-tracking method has been implemented to numerically study the dynamics of the capsule in the channel of interest. Several cases have been simulated to quantify the influence of the parameters involved in this problem such as the channel flow rate, capsule deformability, frequency of oscillation, and the type of applied mechanism for inducing flow oscillations. In all cases, the capsule blockage ratio and the initial location are the same, and it is tracked until it reaches its equilibrium position. The capability to focus the capsule in a short microchannel with oscillatory flow has been observed for capsule deformabilities and mechanisms to induce the oscillations used in our study. Nevertheless, there is a limit to the channel flow rate beyond which, there is no single focal point for the capsule. Another advantage of having an oscillatory microchannel flow is the ability to control the capsule focal point by changing the oscillation frequency according to the cases presented in the current study. The capsule focusing point also depends on its deformability, flow rate, and the form of the imposed periodic pressure gradient; more deformable capsules with lower maximum velocity focus closer to the channel center. Also, the difference between the capsule equilibrium point in steady and oscillatory flows is affected by the capsule stiffness and the device flow rate. Furthermore, increasing the oscillation frequency, capsule rigidity, and system flow rate shorten the essential device length. </div><div><br></div><div>Although the oscillation frequency can provide us with new particle equilibrium positions, especially ones between the channel center and wall that can be very beneficial for separation purposes, it has the shortcoming of having a zero net throughput. To address this restriction, a steady component has been added to the formerly defined oscillatory flow to make it pulsating. Furthermore, this type of flow adds more new equilibrium points because it behaves similarly to a pure oscillatory flow with an equivalent frequency in that regard. They also enable the presence of droplets at high Ca or Re that could break up in the steady or a very low-frequency regime. Therefore, we perform new numerical simulations of a deformable droplet suspended in steady, oscillatory, and pulsating microchannel flows. We have observed fluctuations in the trajectory of the drop and have shown that the amplitude of these oscillations, the average of the oscillatory deformation, and the average migration velocity decrease by increasing the frequency. The dependence of the drop focal point on the shape of the velocity profile has been investigated as well. It has been explored that this equilibrium position moves towards the wall in a plug-like profile, which is the case at very high frequencies. Moreover, due to the expensive cost of these simulations, a recursive version of the Multi Fidelity Gaussian processes (MFGP) has been used to replace the numerous high-fidelity (or fine-grid) simulations that cannot be afforded numerically. The MFGP algorithm is used to predict the equilibrium distance of the drop from the channel center for a wide range of the input parameters, namely Ca and frequency, at a constant Re. It performs exceptionally well by having an average R^2 score of 0.986 on 500 random test sets.</div><div><br></div><div>The presence of lift forces is the main factor that defines the dynamics of the drop in the microchannel. The last part of this work will be dedicated to extracting the active lift force profiles and identify their relationships with the parameters involved to shed light on the underlying physics. This will be based on a novel methodology that solely depends on the drop trajectory. Assuming a constant Re, we then compare steady lift forces at different Ca numbers and oscillatory ones at the same constant Ca. We will then define analytical equations for the obtained lift profiles using non-linear regression and predict their key coefficients over a continuous range of inputs using MFGP.</div>

Swimming is a fundamental feature in many living systems. Biological microorganisms move in the search of food, appropriate pH, temperature, mate and for many other elements crucial for life. A classic example is sperm cell, which travels thousands of its body length in the complex genital tract of females to reach the egg. Inspired by such unique character and diversified motion abilities of the biological world, researchers have always been intrigued to create small artificial microbots which could swim and perform complex tasks. In his famous talk ’There is plenty of room at the bottom’ in 1960, Richard Feynman suggested designing swallowable doctors which could travel in the blood vessels and perform the surgery. Although seemingly exquisite and far-fetched, this idea laid the foundation stone to pave the path towards building autonomously propelled artificial machines with applications ranging from targeted drug delivery to environmental remediation. However, considerable challenges are yet to be addressed before developing fully functional artificial machines, especially in the biomedical applications. For instance, directed transport in vivo, using man-made artificial machines face many obstacles starting from their fabrication, fuels for powering them and their interactions with the surroundings. Rapid changes in the environment in vivo, would make it difficult in selecting the ideal material and shape design of the microswimmer and would most probably require a flexible structure which could potentially squeeze itself and easily pass through small cavities. With most of the swimmers, in the past, being designed from inorganic materials, leave them unsuitable for biological applications. In addition, the environments inside an animal body is dominated by various complexity such as flows of bodily fluids, cavities and soft tissues. In laboratory settings, often these peculiarities are ignored as mostly the motion behavior is tested in stagnant conditions on solid substrates and it is unclear how would an artificial machine will behave in such complex environments. In this thesis, we combined the advances in microfluidics to benefit the microswimmer research manifold. In the last few years, microfluidics and micromotors have been used together in various instances because of their co-sharing regime of low Reynolds number and excellent fluid manipulation abilities at the microscale. In addition, microfluidics offer unique opportunities in designing structures with well-engineered shapes. With these points in mind, in this thesis, we used microfluidics to fabricate microswimmers and design custom made environments to mimic the complexity present in vivo, and to study the feedback of artificial swimmers in them. Specifically, in the first part of the thesis, two microfluidic strategies namely droplet microfluidics and stop-flow lithography were investigated to design hydrogel-based micromotors. Besides, in the next part, we developed complex environments and studied the motion behavior of conventional microswimmers in them. In the first subpart of the thesis, using droplet microfluidics, we designed polyacrylamide and poly (ethylene glycol) diacrylate (PEGDA) based Janus droplets using co-flowing phases with enzyme immobilized in one of the phases to confer asymmetry. The droplets were polymerized on-chip using UV polymerization. We found that the polyacrylamide and PEGDA 565 particles did not result into efficient bubble production when suspended in H2O2 solution and we explain this behaviour using the analogy of smaller pore size and possible poisoning of the enzyme by acrylamide. But, when a 10 v/v% PEGDA 700 was selected as the polymer material, it resulted in very efficient bubble evolution, although the Janus geometry was compromised which restricted swimming for these particles. The second subpart dealt with applying stop-flow lithography technique for designing hydrogel micromotors with different shapes and these shapes corresponded to different swimming modes. Exploiting laminar flow in the low Reynolds number region in the microfluidics channels, we fabricated micromotors with variable composition, shape and controlled active regions. Furthermore, we studied the different trajectories resulting from the complex interactions between swimmer body and fluid dynamics around it and connected them to the theoretical findings. We found close agreement between the experimental results and the theoretical outcomes: I-shaped structure behaved as a pump, U-shaped as a propeller and S-shaped as a rotor. Post fabrication, during real applications, the micromotors will be exposed to complex environments for instance interfaces and flows. To evaluate the feedback of microswimmers in these situations, in the next two sections, we designed custom made environments using microfluidics and we studied the response of well-studied Janus microswimmers in them. It should be noted that in the following two sections we used Janus particles rather than the bubble driven swimmers (fabricated in the first section) for simplicity. In this section, we designed an oil-water interface using a special microfluidic trap design and explored the motion behaviour of a very well-studied Pt@SiO2 Janus micromotors on them. The chip geometry facilitated on-demand merging of a droplet of particles and the ‘fuel’ (H2O2) inside the trap. Additionally, the large surface of the trap resulted in high surface energy which was compensated by partial wetting of the glass substrate. This partial wetting created patches of oil on the glass which we refer to as ‘oil dimples’. The dimples gave us the unique opportunity to directly compare the propulsion and performance of Janus motors at both interfaces (oil-water and solid-water) within the same setup and under similar experimental conditions. The swimming pattern and the speed values were found to be similar at the two interfaces and we conjecture an interplay of various factors such as microscale friction, lubrication, surface locking by the surfactant, reaction product absorption by oil and potential Marangoni influences for this similarity. In the next section, we designed a laminar flowing system using a square glass capillary and studied the response of a spherically symmetrical Janus micromotor in the conditions of flow. Previously, in the literature the response of Pt@SiO2, which is a model pusher-type micromotor, has been studied and they have been demonstrated to migrate cross-stream when the flow is imposed. In this thesis, we introduce a Cu@SiO2 colloid which we hypothesize to resemble a puller-type configuration based on theoretical flow field calculations. Additionally, in the literature, it has been predicted that pullers would exhibit upstream migration when placed under the conditions of flow. Indeed, when placed under flow, these particles migrate upstream, resembling many of the swimmers from biological world. These experimental findings are recovered theoretically using a simple squirmer model in puller configuration. The model also predicted a unique jumping behaviour for these particles, at very high flow rate. When increasing the flow rate in the experiments, we actually capture this characteristics. Finally, based on the theoretical flow field calculations and particularly their upstream response in the imposed flow, we conjecture a puller configuration for Cu@SiO2 micromotors. To sum up, this thesis made important advances by creating a number of different shapes of microswimmers and designing complex environments using microfluidics in which microswimmers can be placed and their response can be studied. Although, in this thesis we emphasized on Janus particles, in future, these custom-made environments can be used to assess the behaviour of other microswimmers including biological ones. While still many engineering and medical problems need to be solved before fully functional applications of artificial microswimmers are realized, manifestations of various shape designs and understanding their behaviours in complex surroundings are the first crucial steps.:Contents: Acknowledgements List of Abbreviations 1. Introduction 2. Fundamentals of active matter and microfluidics 2.1. Active matter 2.1.1. Physical fundamentals of motion at microscale 2.1.2. Biological microswimmers 2.2. Review Paper: Microfluidics for microswimmers 3. Aims and Motivation 4. Results and Discussion 4.1. Microfluidics for fabrication of microswimmers 4.1.1. Introduction 4.1.2. Droplet microfluidics 4.1.3. Stop-flow lithography 4.1.4. Paper - Fundamental Modes of Swimming Correspond to Fundamental Modes of Shape: Engineering I–, U–, and S– Shaped Swimmers 4.2. Microfluidics for specific environments: Interfaces 4.2.1. Introduction 4.2.2. Paper - Study of Active Janus Particles in the Presence of an Engineered Oil–Water Interface 4.3. Microfluidics for specific environments: Flow 4.3.1. Introduction 4.3.2. Paper - Upstream rheotaxis of catalytic Janus spheres 5. Summary and Final Remarks 6. Experimental Details 6.1. Fabrication of hydrogel particles using droplet microfluidics 6.2. Characterization of the hydrogel particles 6.3. Motion studies of the hydrogel particles A. Appendix A.1. Droplet microfluidics A.2. Stop-flow lithography A.3. Microfluidics for specific environments: Interfaces A.4. Microfluidics for specific environments: Flow B. List of publications Bibliography C. Erklärung