Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.

Microfluidics deals with the behavior, control and manipulation of fluids which are confined at micrometer length scale. It has important application in lab-on-a chip technology, micro-propulsion, additive manufacturing, and micro-thermal technologies. Microfluidics has been widely used in detection, separation, transportation, and mixing of fluids and particles. The work carried out for the thesis to study the fluid-structure interaction in micro-channel involves an experimental part and a simulation part. In the experimental part the characterization of biofluid (RBC in BSA) is carried out based on the power law of fluid and flow behavior is studied. Also the dependence of fluid concentration on the viscosity in the channel is studied. The results are analyzed. Transition of fluid behavior from non-Newtonian shear thickening to non-Newtonian shear thinning is observed when the RBC concentration varies from 5.5×106 to 5.5×107 cells/ml in the channel. From the viscosity measurements of the biofluid it is observed that the average viscosity in the channel increases on increasing concentration of the fluid for shear thickening fluids. In the simulation part, interaction behavior of biomolecule DNA is studied in the channel containing biofluid which is characterized in the experimental part. Cell free DNAs are common problem in infectious disease detection. Based on the assumptions of the WLC model, DNA strand is assumed as a one dimensional elastic member with its one end fixed at the channel wall and the other end free to move in the fluid. Bent and straight DNAs are considered for the study. Multiple scales are involved in this problem which is not fully understood. DNA strands in the channel are exposed to different forces in the channel which are mainly due to the pressure and viscous effects. Numerical simulations are carried out for the multiphysics problem of DNA in the fluid using a coupled multiphysics finite element scheme and the results are obtained. Same procedure is carried out considering smaller channels and also for PBS solution as background fluid to obtain consistent results. It is found that when the channel width increases the tip displacement of DNA decreases. It was observed that DNA tip displacement is more in the channel when its end-to-end length is approximately half the width of the channel. Potential application of these modeling and simulation are in molecular screening processes to improve the performance of microfluidic DNA chips, and in design of micro-channel structures of microfluidic devices.

Le marché du diagnostic connait un essor considérable depuis l’avènement de labiologie moléculaire. Plus précis et souvent plus rapide, le diagnostic moléculaire in vitro(DIV) est de plus en plus utilisé dans les laboratoires d’analyses médicales. L’ensemble destests dédiés au marché du DIV répond à des contraintes socio-économiques très précisescomme : la fiabilité du résultat, le délai de réponse court, le faible coût et la facilitéd’utilisation. Les indicateurs socio-économiques montrent que la technologie des biopuces estun potentiel bon candidat pour répondre aux attentes du marché. En effet, cet outil permetl’analyse simultanée de plusieurs dizaines voire centaines de séquences nucléiques et doncl’identification d’autant d’organismes en une seule analyse. Cette technologie s’inscrit encomplément de la PCR en apportant l’avantage de l’analyse multiplexée à moyen débit. Deplus, elle permet de donner une réponse globale de la multiplicité des espèces présentes dansl’échantillon sans avoir besoin de passer par une étape de culture. Néanmoins, cettetechnologie n’est pas optimisée pour le marché du DIV. En effet, son usage est complexe, peurobuste et trop cher pour concurrencer les méthodes actuelles (microbiologie pasteurienne,PCR, Elisa, etc..). Dans le but de réduire le coût de fabrication des biopuces à ADN, il estdonc nécessaire de développer des méthodes alternatives. Dans un premier temps, l’objectif de cette thèse Cifre a été de mettre au point unprototype nouveau de dépôt de biomolécules basé sur la lithographie douce, permettant dedéposer les oligonucléotides sondes de façon multiplexée et selon des motifs micrométriques.Cette nouvelle technologie a été évaluée par rapport aux technologies de références. Puis,nous avons développé un procédé innovant de double fonctionnalisation de surface. Ceprocédé simple et rapide a pour avantages de fonctionnaliser la biopuce avec la chimie desurface et les sondes en une seule étape et d’augmenter les signaux d’hybridation. La secondepartie de la thèse a été de coupler cette nouvelle technologie à la détection des événementsd’hybridation sans marquage en utilisant la diffraction de la lumière. La principale différenceavec la méthode de détection par fluorescence repose sur l’adressage des sondes. En effet, ledépôt doit être réalisé sous forme de réseaux de lignes nanométriques diffractants de façon àce que l'interaction entre les molécules déposées et les cibles qui interagissent soit trèssensible. Cette seconde phase du projet a été très ambitieuse et innovante. La faisabilité decette méthode de détection, démontrée par des simulations théoriques, a fait l’objet d’untravail d’optimisation très important et les résultats obtenus montrent que cette technologiesans marquage est possible. / The diagnosis market increased since the advent of molecular biology. More precise and often faster, the in vitro molecular diagnosis (DIV) is more and more used in medical analyses laboratories. DNA chips technology seems to be a good candidate to answer the market expectations. Indeed, this tool allows making several hundreds of analyses simultaneously. Furthermore, it allows giving a global answer of all the present species in the sample without the need of a culture step. Nevertheless, this technology is not optimized for the market of the DIV. Indeed, its use is complex and too expensive in comparison with the current methods (Pasteur microbiology, PCR, Elisa, etc.). So it is necessary to develop an alternative method to reduce the manufacturing cost and simplify the use of DNA chips. First, the goal of this industrial PhD Cifre supported by the Dendris Company was to complete a new prototype of biomolecules deposition based on soft lithography, allowing multiplexing the deposition of oligonucleotides probes along micro and nanometric patterns.This new technology was compared with the reference technologies. Then, we developed an innovative process of surface co-functionalization. This simple and fast process permits to functionalize the DNA chips with both surface chemistry and probes in a single step and to increase the hybridization signals. The second part of this PhD thesis was to couple this new technology with label-free detection using light diffraction. The main difference with fluorescence-based detection was about probes patterning. Indeed, we needed to generate molecular gratings of nanometric lines to diffract efficiently light from a laser beam. We showed that the absolute diffraction intensity increase with the gratings thickness, which is directly correlated with, probes and targets interactions. The second phase of the project was very ambitious and innovative because we demonstrated the feasibility of this label-free detection. And now we can think that this technology will appear as an alternative method for the diagnosis