In this doctoral thesis we study novel analogues based on R06 aptamers and targeting TAR hairpins of the HIV virus by means of surface plasmon resonance biosensor, which allows for sensitive and real-time monitoring of molecular interactions. We investigate seven different modifications placed at nine different positions on the R06 aptamer in order to find out their applicability in the construction of efficient and stable anti-TAR oligonucleotides. We also determine which positions are suitable for substitutions with a modification and interpret the results in the context of the local nucleotide geometries and interactions in the TAR/anti-TAR complex. In this doctoral thesis we further develop a new fluidic system. This fluidic system eliminates sample dispersion and intermixing effects and thus enables accurate monitoring of molecular interactions on the surface of an SPR chip. We also characterize experimental conditions on the surface of an oligonucleotide chip and their relations towards bio-molecular assays. Specifically, we study the shielding effect of monovalent and divalent cations, which are crucial for the interaction of negatively charged oligonucleotides.

No description available.

Ce travail de thèse porte sur le développement technologique d’outils miniaturiséspour l’exploration de diagrammes de phase de fluides complexes (dispersions colloïdales,solutions de polymères ou tensioactifs, etc). Les outils élaborés permettent dedéterminer des diagrammes de phase par une approche continue à l’aide de la microfluidique.Ils sont basés sur deux types de procédés membranaires différents : la pervaporation(mécanisme d’évaporation de solvant) et la dialyse (mécanisme d’échangesosmotiques). En s’appuyant sur le processus de pervaporation, il a été montré théoriquementet expérimentalement qu’il existe une géométrie pour laquelle le séchageconfiné est homogène. Il est donc possible de construire des diagrammes de phase demélanges à plusieurs composants de l’échelle moléculaire aux colloïdes. Une étudeconsacrée à la compréhension de la complexité du séchage des nanoparticules de silicecommerciales dans un canal microfluidique de type microévaporateur a été miseen place. La cinétique de concentration des particules est décrite jusqu’à la formationd’un état dense ainsi que les divers phénomènes liés au séchage comme l’existenced’une transition de phase dans un système colloïdal, l’apparition de fractures ou la délaminationdu matériau dense. Un nouvel outil microfluidique intégrant une membranede type dialyse offre la possibilité de contrôler les échanges osmotiques à l’échelle dunanolitre. Le protocole de fabrication ainsi que le dimensionnement de la géométriesont présentés. Grâce à cet outil, il est possible de mesurer des pressions osmotiquesde dispersions colloïdales. / This work deals with the technological development of miniaturized tools for theexploration of the phase diagram of complex fluids (colloidal dispersions, solutions ofpolymers or surfactants, etc). The microfluidic tools we elaborated make it possibleto determine phase diagrams of a series of formulations of complex fluids by consumingonly minute amounts of samples. These devices exploit two types of membraneprocesses to concentrate the chemical species : pervaporation (solvent evaporationthrough a dense membrane) and dialysis (osmotic exchanges through a membrane).Concerning the case of pervaporation, we demonstrated theoretically and experimentallythat a specific microfluidic design exists for which concentration fields of chemicalspecies remain spatially homogeneous along the kinetic path followed withinthe phase diagram. Then, it enables to obtain phase diagrams of multi-componentsmixtures from molecular compounds up to colloids, at the nanolitre scale. We reporta study concerning the understanding of the drying process of commercial silica nanoparticlesusing a dedicated microfluidic experiment involving pervaporation. Wepresent the kinetics of the concentration of the particles within the channel up to theformation of a dense colloidal packed bed which invades the channel at a controlledrate. We developed an original microfluidic tool integrating a dialysis membranewhich makes it possible to control osmotic exchanges at the nanoliter scale. We reportthe protocol of microfabrication of this chip and its specific geometry.We presentpreliminary results showing that this tool can be used to measure osmotic pressures ofcolloidal suspensions.

I den här rapporten undersöks hur en vävd textil kan fungera som ett hjälpmedel i analys av vätskor, såsom förorenat vatten eller blod från människor och djur. Det finns i dagsläget ett stort forskningsområde, kallat mikrofluidik, som behandlar förflyttning av vätska i kanaler på mikrometerstora ytor, där det här projektet till viss del kan hjälpa forskningen på området att komma framåt ytterligare ett steg.   Undersökningen har genomförts med hjälp av tester i laboratorium där en väv i polyeten, med kanaler i Coolmax® (polyester) för att transportera vätskan har använts. En mängd olika testomgångar med olika fokus, har genomförts: test i bitar med raka kanaler, test där wickingen avbrutits med hjälp av sax, test där wickingen har pausats på olika sätt för att sedan startas på nytt samt ett mindre antal tester där försök till styrning av vätskan. Syftet har varit att undersöka huruvida alla sex utvalda vätskor (metylenblått, mjölk, nötblod, olivolja, Poly(3,4-ethylenedioxythiophene) och syntetisk urin) har en förmåga att wicka och om det finns skillnader mellan hur långt vätskorna förflyttar sig.   Wickingtesterna har genomförts i både horisontellt och vertikalt läge, detta för att se om och i så fall hur mycket det skiljer, gällande hur långt en vätska flödar i kanalen. Det som framkommit i projektet är att alla vätskorna hade en förmåga att wicka. Metylenblått förflyttade sig längst i horisontellt läge medan urin förflyttades längst i vertikalt läge. Nötblodet förflyttade sig kortast sträcka i både horisontellt och vertikalt läge. Det som däremot har varit svårt att fastställa är vad skillnaderna egentligen beror på. Baserat på matematiska formler för wicking har det konstaterats att vätskornas kontaktvinkel bör ha betydelse, men detta har dessvärre inte kunnat undersökas i det här projektet. / This thesis examines how a woven textile can act as an aid in the analysis of fluids, such as contaminated water or blood from humans and animals. There is currently a large research area, called microfluidics, which deals with the movement of fluid in channels on micrometer-sized surfaces, where this project can, to some extent, fill some gaps and open for further questions in other parts.   The study has been carried out by using laboratory tests where a polyethylene weave, with channels in Coolmax® (polyester) for transporting the liquid has been used. Several different test rounds with a little different focus have been carried out: test in straight pieces, tests where the wicking has been interrupted by scissors, tests where the wicking has been paused and then restarted, and a smaller number of tests where attempts to control and navigate the fluid has been tested. The purpose has been to investigate whether all six selected fluids (methylene blue, milk, blood from bovine, olive oil, poly (3,4-ethylenedioxythiophene) and synthetic urine) have the ability of wicking and if there are differences between the fluids, and how far they reach.   The wicking tests have been carried out in both horizontal and vertical positions, to see if and if so, how much it differs, how far a fluid reaches. What emerged from the project is that all the liquids had the ability to wick. Methylene blue was the fluid that moved furthest in the horizontal position while urine moved furthest in the vertical position. The blood from bovine moved the shortest distance in both horizontal and vertical positions. What has, however, been difficult to determine is what the differences really depend on. Based on mathematical formulas for wicking, it has been found that the contact angle of the liquids should be important, but this have not been investigated in this project.

Ce travail s'inscrit dans le contexte du retraitement du combustible irradié dans l'industrie nucléaire. La gestion du combustible usé fait partie des enjeux majeurs de l'industrie nucléaire aujourd'hui. Ses vastes implications sont de nature économique, politique et écologique. Puisque le combustible irradié contient 97 % des matières valorisables, de nombreux pays ont choisi de retraiter le combustible, non tant pour des raisons économiques que pour le besoin de réduire la quantité en déchets radiotoxiques. Le procédé de séparation le plus répandu est connu sous le nom PUREX et consiste à diluer le combustible dans une solution d'acide nitrique afn d'en extraire les matières valorisables, comme notamment l'uranium et le plutonium. Le procédé est soumis à des strictes contrôles qui s'effectuent au présent par prélèvement et analyse manuel des flux radiotoxiques. Il n'existe cependant peu d'outils pour la supervision du procédé en ligne. Ces travaux visent alors à développer un capteur adapté à cet environnement de mesure à la fois acide et ionisant. Les verres borosilicates étant répandus pour leur inertie chimique, nous proposons l'étude d'un capteur optique fondé sur le substrat de verre Borofloat 33 de Schott. Le capteur étudié et réalisé a été fabriqué grâce à deux technologies différentes : l'optique intégrée sur verre par échange d'ions pour la fabrication de fonction de guidage optique, et la microfluidique pour la gestion des flux acides au sein du capteur. L'approche optique permet de répondre aux besoins de polyvalence, de sensibilité et d'immunité au rayonnement électromagnétique. La microfluidique permet, quant à elle, de travailler sur des très faibles volumes d'échantillon, réduisant ainsi la radiotoxicité des flux d'analyse. Le principe de mesure du capteur repose sur l'effet photothermique, induit dans le fluide par absorption optique d'un faisceau laser d'excitation. L'absorption entraîne un changement de l'indice de réfraction du fluide qui est sondé par un interféromètre de Young, intégré sur la puce. Le volume sondé au sein du canal était de (33,5 ± 3,5) pl. Le changement d'indice de réfraction à la limite de détection était de ∆n_min = 1,2 × 10−6 , nous permettant de détecter une concentration minimale de cobalt(II) dans de l'éthanol de c_min = 6 × 10−4 mol/l, équivalent à un coefficient d'absorption de alpha_min = 1,2 × 10−2 cm−1. À la limite de détection du capteur, une quantité de N_min = (20 ± 2) fmol de cobalt(II) peut être détectée. La longueur d'interaction était de li = 14,9 µm et par conséquent l'absorbance minimale détectable égal K_min = (1,56±0,12)×10−5. / This work has been done in the context of fuel reprocessing in the nuclear industry. In fact, the handling of nuclear waste is one of the major issues in the nuclear industry. Its implications reach from economical to political to ecological dimensions. Since used nuclear fuel consists of 97 % of recyclable substances, many countries have chosen to reprocess used fuel, not only for economical reasons but also to limit the quantity of nuclear waste. The most widely employed extraction technique is the PUREX process, where the used fuel is diluted in nitric acid. The recyclable compounds can then be extracted by solvent techniques. Such processes need to be monitored crucially. However, nowadays, the process supervision is carried out by manually sampling the radioactive fluents and analyzing them in external laboratories. Not only prone to potential risks, this approach is little responsive and produces radiotoxic samples that cannot be reintroduced in the nuclear fuel cycle. In this study, we therefore present the development of a microfluidic glass sensor, based on the detection of a photothermal effect induced in the sample fluid. Microfluidics allows fluid handling on a microliter-scale and can therefore significantly reduce the sample volume and thereby the radiotoxcicity of the analyzed fluids. Photothermal spectrometry is well suited for small-scale sample analysis, since its sensitivity does not rely on the length of optical interaction with the analyte. The photothermal effect is a local refractive index variation due to the absorption of photons by the analyte species which are contained in the sample. On the sensor chip, the index refraction change is being sensed by an integrated Young interferometer, made by ion-exchange in glass. The probed volume in the channel was (33.5 ± 3.5) pl. The interferometric system can sense refractive index changes as low as ∆n_min = 1.2 × 10−6 , allowing to detect a minimum concentration of cobalt(II) in ethanol c_min = 6 × 10−4 mol/l, which is equivalent to an absorption coefficient of alpha_min = 1.2 × 10−2 cm−1 . At the detection limit, we could sense an absolute quantity of cobalt(II) of N_min = (20 ± 2) fmol. The interaction length between the excitation light and the sensing zone was li = 14.9 µm leading to a minimum detectable absorbance of K_min = (1.56 ± 0.12) × 10−5 .

L’interférométrie par retro-injection optique (OFI) est une technique de détection émergente pour les systèmes fluidiques. Son principe est basé sur la modulation de la puissance et/ou de la tension de polarisation d’une diode laser induites par interférence entre le faisceau propre de la cavité laser et la lumière réfléchie ou rétro-diffusée par une cible distante. Grâce à l’effet Doppler, cette technique permet de mesurer précisément la vitesse de particules en mouvement dans un fluide, et de répondre aux besoins croissants de mesure de débit dans les systèmes d’analyse biomédicale ou chimique.Dans cette thèse, les performances de la vélocimétrie par rétro-injection optique sont étudiées théoriquement et expérimentalement pour le cas de micro-canaux fluidiques. Un nouveau modèle numérique multi-physique (optique, optoélectronique et fluidique) est développé pour reproduire les spectres Doppler expérimentaux. En particulier, les effets de la concentration en particules, de la distribution angulaire de la diffusion du laser par les particules, ainsi que du profil d’écoulement dans le canal sont pris en compte. Un bon accord est obtenu entre les vitesses d’écoulement théoriques et expérimentales. Ce modèle est également appliqué avec succès à la mesure de la vitesse locale dans un micro-canal et à l’analyse de l’impact sur le signal des configurations particulières de canal. Enfin, la conception d’un capteur OFI tirant parti des avantages des Lasers à Cavité Verticale à Emission par la Surface (VCSEL) est proposée. Grâce au développement de techniques de microfabrication à base de matériaux polymères, un premier démonstrateur composé d’un VCSEL à lentille intégrée est réalisé et testé sans aucune optique macroscopique additionnelle. Les résultats obtenus en termes de mesure de flux sur des canaux micro-fluidiques de tailles différentes valident l’intérêt de cette approche et ouvrent la voie vers la réalisation de capteurs OFI ultra-compacts. / Optical feedback interferometry (OFI) is an emerging sensing technique which has been studied in fluidic systems. This sensing scheme is based on the modulation of the laser emission output power and/or the junction voltage induced by the interaction between the back-scattered light from a distant target and the laser inner cavity light. Thanks to the Doppler Effect, OFI can precisely measure the velocity of seeding particles in flowing liquids which is much required in chemical engineering and biomedical fields. In the present thesis, optical feedback interferometry performance for microscale flow sensing is studied theoretically and experimentally. A new numerical modeling approach based on multi-physics numerical simulations for OFI signal simulation in the micro-scale flowmetry configuration is presented that highlight the sensor performances. In this model, many factors are involved such as particle concentration and laser-particle scattering angle distribution and flow velocity distribution. The flow rate measurement shows good agreement with the modeling. The implementation of OFI based sensors in multiple fluidic systems, investigating the impact of the fluidic chip specific configuration on the sensor signal.Finally, a compact OFI flowmetry sensor based on Vertical-Cavity Surface-Emitting Lasers (VCSELs) using micro optical fabrication techniques is demonstrated as well. The simulation method for the design and the microfabrication procedures are detailed. After an evaluation of the experimental results, the capabilities of this new OFI sensor in microfluidic measurements are emphasized, thus demonstrating an open path towards ultra-compact microfluidic systems based on the OFI sensing technique.

abstract: Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large sample volumes from over a wide area and transporting them to laboratory testing facilities, which fail to provide any real-time information. This dissertation evaluates the systems currently utilized for in-situ field analyses and the issues hampering the successful deployment of such bioanalytial instruments for environmental applications. The design and development of high throughput, low power, and autonomous Polymerase Chain Reaction (PCR) instruments, amenable for portable field operations capable of providing quantitative results is presented here as part of this dissertation. A number of novel innovations have been reported here as part of this work in microfluidic design, PCR thermocycler design, optical design and systems integration. Emulsion microfluidics in conjunction with fluorinated oils and Teflon tubing have been used for the fluidic module that reduces cross-contamination eliminating the need for disposable components or constant cleaning. A cylindrical heater has been designed with the tubing wrapped around fixed temperature zones enabling continuous operation. Fluorescence excitation and detection have been achieved by using a light emitting diode (LED) as the excitation source and a photomultiplier tube (PMT) as the detector. Real-time quantitative PCR results were obtained by using multi-channel fluorescence excitation and detection using LED, optical fibers and a 64-channel multi-anode PMT for measuring continuous real-time fluorescence. The instrument was evaluated by comparing the results obtained with those obtained from a commercial instrument and found to be comparable. To further improve the design and enhance its field portability, this dissertation also presents a framework for the instrumentation necessary for a portable digital PCR platform to achieve higher throughputs with lower power. Both systems were designed such that it can easily couple with any upstream platform capable of providing nucleic acid for analysis using standard fluidic connections. Consequently, these instruments can be used not only in environmental applications, but portable diagnostics applications as well. / Dissertation/Thesis / Ph.D. Electrical Engineering 2013

[pt] Materiais nanoestruturados como nanocristais semicondutores de telureto de cádmio (QDs de CdTe) e nanopartículas metálicas de prata (NPsAg) têm sido utilizados como nanosondas analíticas, explorando suas propriedades de luminescência e de ressonância de superfície plasmônica localizada (LSPR), respectivamente, sejam em dispersão coloidal ou em filmes finos. Em função das suas configurações experimentais, sistemas microfluídicos podem ser utilizados tanto para síntese de materiais nanoestruturados quanto para análise de analitos de interesses biológicos. No presente estudo, QDs-CdTe encapados com ácido tioglicólico (TGA) foram sintetizados em batelada e em regime de fluxo contínuo a partir da injeção dos precursores de cádmio e telúrio por bombas-seringas para um sistema de tubos de aço passando por fornos tubulares horizontais com controladores de temperatura (110-140 graus Celsius). Para otimizar os parâmetros experimentais foram variados a taxa de vazão volumétrica (0,15 - 0,03 mL min(-1)) e a razão molar de Cd:Te (1:0,3 - 1:1,5). Os resultados demonstraram que o efeito da razão molar na síntese de QDs apresentou ser mais significativo em comparação à variação da temperatura, obtendo QDs com FWHM de 64 – 86 nm. Filmes luminescentes poliméricos de PVA e PDMS foram desenvolvidos pelas técnicas de impregnação, mistura de QDs na matriz polimérica e por spin coating. Pela técnica de spin coating foram produzidos filmes de 58,7 nm. Filmes de QDs sobre substrato de vidro foram obtidos pelo processo de silanização da superfície do vidro. Todos os filmes apresentaram instabilidade de luminescência ao longo do tempo. Dispersões coloidais de NPsAg revestidas com ligantes orgânicos citrato e tartarato, nas razões Ag+:ligante (1:1 e 1:0,5), foram sintetizadas a partir da injeção dos ligantes e nitrato de prata por bombas-seringas em um microrreator tubular polimérico. As NPsAg-citrato e NPsAg-tartarato apresentaram cargas superficiais negativas e tamanhos médios de 12,5 nm. As bandas LSPR foram observadas para monitorar a interação entre as nanosonda de prata e os fármacos aminoglicosidico em fluxo contínuo mediante um fotômetro acoplado a uma cela de fluxo. Nas concentrações iguais ou maior que 2 × 10(-7) mol L(-1), produziu uma mudança no perfil espectral da nanosonda de NPsAg, com o decaimento do sinal no comprimento de onda 404 nm e o surgimento de uma nova banda em 480 nm, resultante da aglomeração das nanopartículas. Além disso, as NPsAg-tartarato foram depositadas sobre substrato de vidro para realização de filmes fino com objetivo de desenvolver, em parceria com a Universidade Federal de Pernambuco (UFPE), um biosensor baseado na ressonância plasmônica localizada (LSPR) para determinação do antígeno Candida albicans. / [en] Nanostructured materials such as cadmium telluride semiconductor nanocrystals (QDs-CdTe) and silver nanoparticles (NPsAg) have been used as analytical nanoprobes, exploiting their luminescence properties and localized plasmonic surface resonance (LSPR), respectively, both in colloidal suspension or on thin solid films. Due to their experimental set-up, microfluidic systems can be used, both, for synthesis of nanostructured materials and for the analytic detection of biological and pharmaceutical compounds. In the present study, thioglycolic acid (TGA) coated QDs-CdTe were synthesized in batch and in a continuous flow regime from the injection of cadmium and tellurium precursors by syringe pumps into a steel tubes through horizontal tubular furnaces with temperature controllers (110 - 140 Celsius degrees). To optimize the experimental conditions, we modulate the volumetric flow rate (0.15 - 0.03 mL min(-1)) and the Cd:Te molar ratio (1:0.3 - 1:1.5). The results showed that the effect of the molar ratio on the synthesis of QDs was more significant compared to the temperature variation, obtaining QDs with FWHM of 64 - 86 nm. Polimeric luminescent films with PDMS e PVA were developed with impregnation, mixing QDs-TGA in PDMS and PVA and spin coating techniques. By the spin coating technique we produced luminescent film of 58.7 nm thickness. QDs-TGA film on glass substrate were obtained by means of surface silanization.All the film showed luminescence instability over time. Colloidal dispersions of NPsAg coated with the organic citrate and tartrate ligands in the Ag+/ligand ratios (1:1 and 1:0.5) were synthesized from the injection of organic ligands and silver nitrate by syringe pumps into a polymeric tubular micro-reactor. NPsAg-citrate and NPsAg-tartrate presented negative surface charges and average sizes of 12.5. The SPR band was monitored to follow the interation between the silver nanoprobe with kanamycin and neomycin drugs by means of a flow cell coupled to a photometry. At concentrations equal or greater than 2 × 10(-7) mol L(-1) the LSPR band changed its spectral profile. LSPR maximum band, centered at 404 nm, decaied and appeared a new band at 480 nm resulting from the agglomeration of the nanoparticles. Moreover, in a partnership with the Federal University of Pernambuco (UFPE), NPsAg-tartarate were deposited on glass for the realization of thin film with the object to development a biosensor based on localized plasmon resonance (LSPR) for determination of Candida albicans antigen.

Submitted by Liliane Ferreira (ljuvencia30@gmail.com) on 2018-09-03T12:02:08Z No. of bitstreams: 2 Tese - Cyro Lucas Silva Chagas - 2018.pdf: 4698038 bytes, checksum: 54bd125cfa8cf11d8672d79de558c77c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-09-04T11:35:55Z (GMT) No. of bitstreams: 2 Tese - Cyro Lucas Silva Chagas - 2018.pdf: 4698038 bytes, checksum: 54bd125cfa8cf11d8672d79de558c77c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-09-04T11:35:55Z (GMT). No. of bitstreams: 2 Tese - Cyro Lucas Silva Chagas - 2018.pdf: 4698038 bytes, checksum: 54bd125cfa8cf11d8672d79de558c77c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-08-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The development of miniaturized devices promoted a real revolution in modern analytical chemistry. In addition, the improvement of microfabrication technologies has made it possible to create ever smaller and more robust devices. However, most of these devices still demand sophisticated and expensive instrumentation in their manufacturing process, often requiring controlled environments or clean rooms. In view of the need to produce these miniaturized devices in a more accessible way, the present thesis presents the manufacture of alternative, disposable and low cost microfluidic platforms and devices for bioanalytical applications. The methodologies covered in this thesis include: the manufacture of low cost pencil-drawn graphite electrodes on office paper, used in the quantification of inorganic cations (K+ and Na+) in human tears; the manufacture of electrophoresis chips with thermolaminated paper channels with attached graphite electrodes for the monitoring of the electrophoretic separation of biomolecules (albumin and creatinine); and finally, it presents the use of a 3D microfluidic device for the generation of droplets into the microchannel and the manufacturing process of a thermolaminated polyester dispositive for flow injection analysis, both for the analysis of drugs (ascorbic acid and midazolam maleate) in medicines. All analyzes used the same method of capacitively coupled contactless conductivity detection. The proposed graphite electrodes presented excellent analytical performance with good reproducibility. The detection limits found for K+, Na+ and Li+ were 4.9, 6.8 and 9.0 μM, respectively. In addition, the concentration found for K+ and Na+ in the tear samples were, respectively, 20.8 and 101.2 mM for sample A and 20.4 and 111.4 mM for sample B. Experiments using the proposed paper-based microchip have successfully demonstrated the separation of bovine serum albumin and creatinine within 150 s with baseline resolution. The detection limits for albumin and creatinine were 20 and 35 mM, respectively. The quantification of ascorbic acid in a vitamin supplement, through the generation of droplets in the 3D device, was successfully demonstrated with a linear range of 3 to 24 mg/mL and a detection limit of 1.1 mg/mL. The quantification of midazolam maleate in tablets, using a flow injection in the polyester device showed a linear behavior between 0.5 and 4.0 mg/mL and a detection limit of 17 µg/mL. The devices proposed in this thesis allowed the realization of low cost assays with reduced analysis time. In addition, the manufacturing processes demonstrated simplicity and quickness, without the need for sophisticated instrumentation, allowing the use of these devices for applications in clinical analysis and quality control. / O desenvolvimento de dispositivos miniaturizados promoveu uma verdadeira revolução na química analítica moderna. Além disso, o melhoramento das tecnologias de microfabricação possibilitou a criação de dispositivos cada vez menores e mais robustos. Contudo, grande parte destes dispositivos ainda demandam em seu processo de fabricação uma instrumentação sofisticada e de alto custo, necessitando muitas vezes de ambientes controlados ou salas limpas. Tendo em vista a necessidade de se produzir esses dispositivos miniaturizados de uma maneira mais acessível, a presente tese apresenta a fabricação de plataformas e dispositivos microfluídicos alternativos, descartáveis e de baixo custo para aplicações bioanalíticas. As metodologias abordadas nessa tese incluem: a fabricação de eletrodos de grafite de baixo custo desenhados à lápis em papel sulfite, utilizados na quantificação de cátions inorgânicos (K+ e Na+) em lágrima humana; a fabricação de chips de eletroforese com canais de papel termolaminados com eletrodos de grafite de lápis acoplados para o monitoramento da separação eletroforética de biomoléculas (albumina e creatinina); e por fim, apresenta a utilização de um dispositivo microfluídico 3D para a geração de gotas no microcanal e o processo de fabricação de um dispositivo de poliéster termolaminado para análise por injeção em fluxo, ambos para análise de fármacos (ácido ascórbico e maleato de midazolam) em medicamentos. Todas as análises utilizaram o mesmo método de detecção condutométrica sem contato acoplada capacitivamente. Os eletrodos de grafite propostos apresentaram excelente performance analítica com boa reprodutibilidade. Os limites de detecção encontrados para o K+, Na+ e Li+ foram de 4,9, 6,8 e 9,0 µM, respectivamente. Além disso, a concentração encontrada para o K+ e Na+ nas amostras de lágrima foram, respectivamente, de 20,8 e 101,2 mM para a amostra A e 20,4 e 111,4 mM para a amostra B. Os experimentos utilizando o microchip de papel proposto demonstraram com sucesso a separação de albumina de soro bovino e creatinina dentro de 150 s com resolução de linha de base. Os limites de detecção para albumina e creatinina foram 20 e 35 mM, respectivamente. A quantificação de ácido ascórbico em suplemento vitamínico, através da geração de gotas no dispositivo 3D, foi demonstrada com êxito apresentando uma faixa linear entre 3 e 24 mg/mL e limite de detecção igual a 1,1 mg/mL. A quantificação de maleato de midazolam em comprimidos, utilizando injeção em fluxo no dispositivo de poliéster apresentou comportando linear entre 0,5 e 4,0 mg/mL e limite de detecção de 17 µg/mL. Os dispositivos propostos nesta tese possibilitaram a realização de ensaios de baixo custo com tempo de análise reduzido. Além disso, os processos de fabricação demonstraram simplicidade e rapidez, sem a necessidade de instrumentação sofisticada, permitindo a exploração destes dispositivos para aplicações em análises clínicas e de controle de qualidade.

Orientador: Luiz Otavio Saraiva Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecanica / Made available in DSpace on 2018-08-06T16:27:32Z (GMT). No. of bitstreams: 1 Espindola_AlexeyMarques_M.pdf: 1293939 bytes, checksum: 66ab2d16dc552294762d6c3708cda71b (MD5) Previous issue date: 2006 / Resumo: Os sistemas microfluidicos estão evoluindo rapidamente, encontrando vastas aplicações na mais diversas áreas do conhecimento. Os Lab-on-Chips, LOCs, são dispositivos capazes de realizar análises químicas e bioquímicas em um único chip. Este dispositivo pode causar grande impacto no mercado de análises laboratoriais, por este motivo vem ganhando grande atenção Para realizar estas análises os LOCs necessitam de microbombas capazes de transportar quantidades ínfimas de fluidos em seus canais de maneira acurada e uniforme. Desta forma, o interesse em modelar e fabricar microbombas tomou-se uma área fértil para a pesquisa. Neste trabalho foi desenvolvida a modelagem de uma microbomba peristáltica de elastõmero, tipo de bomba mais conveniente para Lab-on-Chips, utilizando a técnica de analogias eletro-mecânicas que consiste em representar um dispositivo por um circuito elétrico equivalente. As análises das simulações podem ser realizadas usando programas de análise de circuitos elétricos. Dois modelos foram apresentados neste trabalho. O primeiro é a reprodução do modelo de bomba criado por Jacques Goulpeau, em que o modelo de uma válvula é extrapolando para toda a microbomba. O segundo contém o circuito elétrico equivalente da bomba completa mostrando a interações entre suas partes. Os resultados mostram que o comportamento da microbomba não pode ser completamente descrito pelo modelo extrapolado a partir de uma válvula, devido às interações entre três válvulas. As simulações do circuito equivalente da bomba completa mostraram que os efeitos das interações entre as válvulas explicam claramente a diferença entre a vazão prevista pelo modelo de Goulpeau e os dados experimentais por ele obtidos, sendo possível ajustar o modelo aos dados experimentais / Abstract: Microfluidies systems are growing rapidly, finding a large nwnber of applications in many fields. Lab-on-ehips, LOC, are deviees that ean perform ehemical and biochemical analyses in a ehip. This device ean cause high impact on laboratorial analyses market, and then it is gaining large attention. In order to execute these analyses on LOC, mieropumps are necessary to transport a tiny quantity of fluid between the channeIs with accuracy and uniformity. Thus, the interests of modeling and fabrication mieropwnps are increasing and become a fertile research field. The goal of this work were a modeling of elastomer peristaltic micropwnp, the most suitable pwnp for LOCs, using the electro- mechanical analogy technique that consist in represent the device in a electrical equivalent networks. Then the simulation analyses can be done on electrical simulation tools. Two models were presented in this work. The first is reproduction of the pwnp model made by Jacques Goulpeau et aI., where the valve model is extrapolated to the whole mieropwnp. The second contains the electrical equivalent circuit that represents the whole device showing the interactions between its eomponents. The results showed that micropump behavior eouldn't completely deseribe by the extrapolated model ftom a valve, because the interactions between the three valves. The simulations of electrical equivalent eircuit of the whole pwnp showed that the interaction between the valves explain the difference between of flow rate foreseen by Goulpeau model and his experimental data, being possible to adjust the model to the experimental data / Mestrado / Mecanica dos Sólidos e Projeto Mecanico / Mestre em Engenharia Mecânica