Micro-devices are developed for uses in targeted drug delivery and microscale manipulation. Here we numerically and analytically study two promising devices in early stages of development. Firstly, we study Armoured Microbubbles (AMBs) which can self-propel as artificial microswimmers or facilitate microfluidic mixing in a channel when held stationary on a wall. Secondly, we study an artificial cilium, which due to its unique design, when placed in an array, easily produces a metachronal wave for fluid transportation. The Armoured Microbubble was designed by our experimental collaborators (group of Philippe Marmottant, University Grenoble Alpes) and consists of a partial hollow sphere, inside which a bubble is caught. Under ultrasound the bubble oscillates, generating a streaming flow in the surrounding fluid and producing a net force. Motivated by the AMB but considering initially a general setup, using matched asymptotic expansions we calculate the streaming flow around a spherical body undergoing arbitrary, but known, small-amplitude surface shape oscillations. We then specialise back to the AMB and consider its excitation under ultrasound, using a potential flow model with mixed boundary conditions, to identify the resonant frequencies and mode shapes, including the dependence of the resonance on the AMB shape parameters. Returning to our general streaming model, we applied the mixed boundary conditions directly to this model, calculating the streaming around the AMB, in good agreement with experiments. Using hydrodynamic images and linear superposition, this model was extended to incorporate one wall, and AMB compounds. We then study the streaming flows generated by arrays of AMBs in confined channels, by modelling each AMB as its leading order behaviour (with corrections where required) and superposing the individual flow fields of all the AMBs. We identified the importance of two confining walls on the streaming flow around the array, and compared these flows to experiments in five cases. Motivated by this setup, we theoretically considered the extension of a two fluid interface passing through an AMB array to quickly identify good AMB arrays for mixing. We then studied the second artificial micro-device: an artificial cilium. Tsumori et. al. produced a cilium of PDMS containing aligned ferromagnetic filings, which beat under a rotating magnetic field. We modelled a similar cilium but assumed paramagnetic filings, using a force model balancing elastic, magnetic and hydrodynamic forces identifying the cilium beat pattern. This agreed with our equilibrium model and asymptotic analysis. We then successfully identified that the cilium applies the most force to the surrounding fluid at an intermediate value of the two dimensionless numbers quantifying the dynamics.

Doctor of Philosophy / Department of Chemistry / Christopher T. Culbertson / My doctoral dissertation consists of three fundamental studies: 1) synthesis of biocompatible materials that can be used as microfluidic substrates, 2) characterizing these materials with respect to properties important to microfluidic fabrication, biochemical separations and concentration enrichment, and 3) employing these novel devices for real world applications in bioanalytical chemistry. The surface properties of a substrate will dramatically affect the resolution and efficiency that can be obtained for a specific CE separation. Thus, the ability to modify the surface is very useful in tailoring a microfluidic chip to a specific separation mode. The substrates we have synthesized for microfluidic devices include metal oxide modified poly(dimethylsiloxane) (PDMS), poly(ethyleneoxide)-PDMS (PEO-PDMS) coblock polymers, and surfactant coated PDMS. The metal oxide modified PDMS materials we synthesized include silica-PDMS, titania-PDMS, vanadia-PDMS and zirconia-PDMS. The surfaces of these materials were characterized using contact angle, X-ray photoelectron spectroscopy (XPS), Raman, transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM) and electroosmotic mobility (EOM) measurements. All of the metal oxide modified PDMS surfaces were significantly more hydrophilic than native PDMS, suggesting potential application in separations of biopolymers. In addition to being more hydrophilic the EOF and zeta potential of the channels were stable and quite durable with aging. Well characterized silane chemistry was used to derivitize the surface of the PDMS metal oxide surfaces allowing a number of different functionalities to be placed on the surface. This method has the potential for wide applicability in many different fields, but specifically for the fabrication of microstructures that need specific surface chemistries. We have also made a number of advancements using sol-gel chemistry and laminar flow within microfluidic channels to fabricate nanoporous membranes. Sol-gel patterned membranes are a simple and facile method of incorporating nanoscale diameter channels within a microfluidic manifold. These membranes have been used to perform preconcentration of amino acids, proteins and small particles for further analysis and separation using CE. We are also using these membranes for further study in desilanization and protein recrystallization studies.

Please read the abstract in the front pages of the file named 00dissertation / Dissertation (MEng (Mechanical))--University of Pretoria, 2007. / Mechanical and Aeronautical Engineering / unrestricted

Microfluidics refers to devices and methods for controlling and manipulating fluid flows at length scales less than a millimeter. Miniaturization of a laboratory to a small device, usually termed as lab-on-a-chip, is an advanced technology that integrates a microfluidic system including channels, mixers, reservoirs, pumps and valves on a micro scale chip and can manipulate very small sample volumes of fluids. While several flow control concepts for microfluidic devices have been developed to date, here flow control concepts based on thermally responsive polymer solutions are presented. In particular, flow control concepts base on the thermally triggered reversible phase change of aqueous solutions of the polymer Pluronic will be discussed. Selective heating of small regions of microfluidic channels, which leads to localized gel formation in these channels and reversible channel blockage, will be used to control a membrane valve that controls flow in a separate channel. This new technology will allow generating inexpensive portable bioanalysis tools where microvalve actuation occurs simply through heaters at a constant pressure source without a need for large external pressure control systems as is currently the case. Furthermore, a concept for controlled cross-channel transport of particles and potentially cells is presented that relies on the continuous regeneration of a gel wall at the diffusive interface of two co-streaming fluids in a microfluidic channel. / Applied Science, Faculty of / Mechanical Engineering, Department of / Graduate

Au cours des dernières décennies, l'étude des puces microfluidiques capables d'exécuter des processus chimiques et biologiques sur quelques centimètres carrés a été un domaine de recherche actif. De telles plateformes offrent un environnement fermé et contrôlable qui permet une mesure reproductible et évite toute contamination externe. Cependant, ces environnements sont fermés, ce qui empêche l'utilisation de sondes de mesure ou d'effecteurs fixés à l'extérieur de la puce microfluidique. Pour répondre à ce besoin, nous proposons d'utiliser des microrobots rotatifs hélicoïdaux évoluant dans un fluide. Les microrobots proposés sont conçus grâce à la lithographie 3D par laser. Ils présentent une forme hélicoïdale de 5.5 µm de diamètre et environ 50 µm de longueur. Une couche mince ferromagnétique déposée sur ces microrobots permet de les propulser et de les contrôler grâce à un champ magnétique tournant homogène.Le premier défi est l'intégration stable de microrobots à l'intérieur d'un environnement microfluidique. Dans cette thèse, nous avons donc d'abord prouvé que ces microrobots peuvent utiliser leur propre mobilité pour s'intégrer individuellement à l'intérieur d'une puce microfluidique en utilisant un microcanal relié à un réservoir ouvert. Pour cela, nous avons développé un mouvement 3D où le microrobot évolue dans le fluide et deux mouvements 2D où il évolue sur une surface. En passant facilement d'un mouvement à l'autre, les microrobots peuvent utiliser les différents avantages de chaque mouvement pour obtenir une mobilité suffisante à cette intégration. Nous avons nommé ce modèle de microrobot "Roll-to-Swimm"(RTS).Ensuite, pour utiliser un microrobot comme capteur de force sur puce microfluidique, il est nécessaire de caractériser la force générée par l'hélice de chaque RTS. Une méthode de caractérisation est proposée, dans laquelle les différents paramètres d'environnement tels que le flux parasite, le gradient de température et l'impact des surfaces, sont contrôlées avec précision grâce à l'environnement microfluidique. Nous en concluons que le modèle de microrobot "RTS" peut appliquer une force de 10 à 45 piconewton avec une erreur maximale de 38 %. La composante principale de cette erreur (73 %) est due à l'évolution de l'aimantation du RTS. Par conséquent, les efforts visant à réduire cette erreur doivent d'abord se concentrer sur la propriété de magnétisation du RTS. Cette erreur peut également être temporairement réduite en caractérisant la RTS juste avant son utilisation dans une expérience.Enfin, nous présentons trois preuves de concept pour démontrer que notre méthode de caractérisation rapproche les microrobots hélicoïdaux des applications potentielles. Tout d'abord, nous mesurons la diminution de la force du RTS lorsqu'il pousse une microbille. Cette mesure est essentielle pour connaitre la force appliquée par le RTS sur un objet ou pour mesurer l'état de surface en utilisant des billes comme interface. Une microbille de 10 µm de diamètre à la pointe du RTS réduit la propulsion de 6 %. Deuxièmement, nous utilisons la caractérisation du RTS pour mesurer la vitesse locale de l'écoulement dans un canal. Puis nous proposons d'utiliser cette mesure de vitesse pour le contrôle du microrobot grâce à un contrôle automatique du RTS qui adapte le type de mouvement en fonction de la vitesse de l'écoulement. Ce contrôle a été testé expérimentalement avec différentes conditions d'écoulement. Troisièmement, nous utilisons la caractérisation du RTS pour effectuer des simulations numériques afin de trouver une stratégie de contrôle dans des microcanaux de taille inférieure à 20 fois le diamètre du RTS. Le modèle de cette simulation a été validé en comparant ces résultats avec des données expérimentales. Finalement, nous proposons un système de contrôle permettant de maintenir le RTS centré à l'intérieur de microcanaux courbes évoluant en 3D, en utilisant seulement une acquisition d'image en 2D. / Microfluidic chips that could perform chemical and biological processes on a few centimeter square footprint have been an active area of research in the past decades. Among other advantages, this platform offers a closed and controllable environment that allows reproducible measurements and avoids external contamination. However, such closed environments prevent the use of tethered probes to measure or apply a specific force on an element inside the microfluidic chip. Therefore we propose to use a helical rotating microrobot inside a microfluidic chip to answer this need. The proposed microrobots are designed with 3D laser lithography, and have a helical shape of 5.5 µm in diameter and around 50 µm length. A thin ferromagnetic layer is deposited on these microrobots which allows us to propel and control them with a homogenous external rotating magnetic field.The first challenge is the stable integration of these microrobots inside microfluidic environments. Therefore, in this thesis we first proved that these microrobots can use their own mobility to integrate themselves selectively (one by one) inside a microfluidic chip through a microchannel connected to an open reservoir. For this, we have developed a 3D motion where the microrobot evolves in the fluid and two different 2D motions where it evolves on a surface. By switching easily from one motion to another, the microrobots can use the different advantages of each motion to get sufficient mobility required for this integration. We named our microrobot design Roll-To-Swimm (RTS) in reference to this characteristic.Then in order to use a microrobot as on-chip force sensor, a precise characterization of the force generated by the helical shape is necessary for each RTS. A characterization method is proposed, where the different environment parameters (parasite flow, temperature gradient and impact of near surfaces on the flow) are controlled precisely thanks to the microfluidic environment. The characterization shows that the force range of the RTS is between 10 and 45 piconewton with a maximum error of 38 %. We also conclude that the main component of this error (73 %) is due to the evolution of the RTS magnetization. Therefore the efforts to reduce this error should first focus on the magnetization property of the RTS. This error can also be temporarily reduced by characterizing the RTS just before its use in another experiment.Finally, we present three different proofs of concept to demonstrate that our characterization method brings helical microrobots closer to potential on-chip force sensing applications. Firstly, we show that it is possible to measure the diminution of the RTS force when it is pushing a micro spherical bead. This is essential toward applying force on an object with this RTS or to use beads as an interface between the RTS and the surface to measure friction forces. A microbead with 10 µm in diameter at the tip of the RTS reduces it propulsion of 6 %.Secondly, we use the RTS characterization to measure local flow speed. We demonstrate this feature by measuring flow profiles in fluid channels. We show the potential use for of microrobot control by proposing an automatic control of the RTS that adapts the motion to the measured flow. This control has been tested experimentally with different flow conditions. Thirdly, we use the characterization of the RTS to perform numerical simulations in order to find a control strategy in small microchannels. Indeed we demonstrate that for microchannels below 20 times the RTS diameter, the channel walls have an impact on the RTS motions. The model of this simulation has been validated by comparing this result with experimental data. Finally we propose a control scheme for maintaining the RTS centered in a curved microchannel by only using a 2D image feedback.

No description available.

Sepsis is an uncontrolled response to infection. Severe sepsis is associated with organ dysfunction, and has mortality rate of 30-50%. Identification of severity of sepsis and prediction on mortality is crucial in making clinical decisions. Recently, cell-free DNA (cfDNA) in blood was found to have high discriminative power in predicting ICU mortality in patients with severe sepsis. In an analysis of 80 severely septic patients, the mean cfDNA level in survivors (1.16±0.13μg/ml) was similar to that of healthy volunteers (0.93±0.76μg/ml), while that of non-survivors (4.65±0.48μg/ml) was notably higher. Therefore, rapid quantification of cfDNA concentration in blood will enable physicians to quickly predict mortality of sepsis and decide on treatment. Current methods for quantification of cfDNA involve multiple steps including centrifugation, DNA-extraction from plasma, and its quantification either through spectroscopic methods or quantitative PCR. The whole process is time consuming, thus is not suitable for immediate bedside assessment. To solve the problems, a microfluidic device is designed and fabricated in this thesis, which is potential for cfDNA quantification directly using blood in 5 minutes. The goal is to use this device for distinguishing survivors or healthy donors from non-survivors in patients with severe sepsis. The two-layer device consists of a sample channel (top) and an accumulation channel (bottom) that intersect each other. The accumulation channel is preloaded with 1% agarose gel, and the blood containing cfDNA and intercalating fluorescent dye is loaded in the sample channel. Fluorescently labeled DNA is able to be trapped and concentrated at the intersection using a DC electric field, and fluorescent intensity of the accumulated DNA is representative of its concentration in the blood. The simulated electric field in the sample channel reveals that both the magnitude and the gradient of electric field reach their maximum values at the intersection. Force analysis shows that DNA was driven into the gel by the dominate electrophoretic force, while red blood cells moved away from the gel due to a strong dielectrophoretic force. In this thesis, 4 types of samples have been used to characterize the performance of the device. It showed that DNA was efficiently accumulated at the intersection, and the fluorescent intensity could be measured using a fluorescent microscope. Samples from healthy donors were able to be distinguished from that of severely septic patients in 5 minutes. However, better resolution was needed for differentiating various cfDNA concentrations in patient samples. The discussion on the effect of applied voltage showed that 9V is an optimized setting compared with 3V and 15V. In addition, it has been proved that the fluorescent reagent could be immobilized in the device and the sample preparation could be absolutely eliminated. In summary, the device proposed in this thesis is capable of distinguishing severely septic patients from healthy donors using clinical plasma in 5 minutes, and is potential to be applied in clinical blood samples. It has low cost, and is ready to be developed into a fully functioned system. This tool can be a valuable addition to the ICU to rapidly assess the severity of sepsis for informed decision making. / Thesis / Master of Applied Science (MASc)

Microfluidics is both a science and a technology offering great and perhaps even revolutionary capabilities to impact the society in the future. However, due to the scaling effects there are unknown phenomena and technology barriers about fluidics in microchannel, material properties in microscale and interactions with fluids are still missing. A systematic investigation has been performed aiming to develop "A Customer Programmable Microfluidic System". This innovative Polydimethylsiloxane (PDMS)-based microfluidic system provides a bio-compatible platform for bio-analysis systems such as Lab-on-a-chip, micro-total-analysis system and biosensors as well as the applications such as micromirrors. The system consists of an array of microfluidic devices and each device containing a multilayer microvalve. The microvalve uses a thermal pneumatic actuation method to switch and/or control the fluid flow in the integrated microchannels. It provides a means to isolate samples of interest and channel them from one location of the system to another based on needs of realizing the customers' desired functions. Along with the fluid flow control properties, the system was developed and tested as an array of micromirrors. An aluminum layer is embedded into the PDMS membrane. The metal was patterned as a network to increase the reflectivity of the membrane, which inherits the deformation of the membrane as a mirror. The deformable mirror is a key element in the adaptive optics. The proposed system utilizes the extraordinary flexibility of PDMS and the addressable control to manipulate the phase of a propagating optical wave front, which in turn can increase the performance of the adaptive optics. Polydimethylsiloxane (PDMS) has been widely used in microfabrication for microfluidic systems. However, few attentions were paid in the past to mechanical properties of PDMS. Importantly there is no report on influences of microfabrication processes which normally involve chemical reactors and biologically reaction processes. A comprehensive study was made in this work to study fundamental issues such as scaling law effects on PDMS properties, chemical emersion and temperature effects on mechanical properties of PDMS, PDMS compositions and resultant properties, as well as bonding strength, etc. Results achieved from this work will provide foundation of future developments of microfluidics utilizing PDMS.

No description available.

No description available.