Design and microfabrication of new automatic human blood sample collection and preparation devices

For self-sampling or collection of blood by health personal related to point-ofcare diagnostics in health rooms, it may often be necessary to perform automatic collection of blood samples. The most important operation that needs to be done when handling whole blood is to be able to combine automatic sample collection with optimal mixing of anticoagulation liquid and weak xatives. In particular before doing any transport of a sample or point-of-care nucleic acid diagnostics (POCNAD) it is very important to x the gene expression at the time of collection. It is also important to concentrate and separate out the white blood cells of interest from the whole blood before further detection. An automatic sample collection module with a microneedle array in combination with a micromixer is proposed for the blood collection in typical nurse or health rooms. An automatic human blood preparation module is also suggested that could be used for pre-mixing, concentration and lyses. Despite that the concept of microneedle has been intensively studied since several decades ago, the fabrication still remains very challenging. Major challenges concern the high aspect ratio of microneedle structure. In addition, the microneedles have to be su ciently strong to avoid fracture and cracks during practical implementation. The other challenge with small microchannel dimensions on a chip is the lack of turbulences (including fluids that operate with Reynolds number smaller than 2000). Hence a long mixing length is required for good mixing quality. This doctoral thesis focus on the following challenges: (i) design and optimize a continuous concentration and separation unit, (ii) optimize and improve the fabrication process of high aspect ratio metallic microneedle, (iii) develop and investigate the mixing performance of a passive planar micromixer with ellipse-like micropillars, (iv) integrate and demonstrate the pretreatment system. Article I reported the design and optimization of non-clogging counter-flow microconcentrator for enriching epidermoid cervical carcinoma cells. The counter-flow concentration unit with turbine blade-like micropillars were proposed in microconcentrator design. Due to the organization of these micropillar units the functionality cause a unique system of continuous concentration and separation. Due to the unusual geometrical-pro les and extraordinary micro fluidic performance, the cells blocking does not occur even at permeate entrances. The excellent concentration ratio of a fi nal microconcentrator was presented in both numerical and experimental results. Article II proposed a simple and low cost micromixer for laminar blood mixing. The design of micromixer unit was modifi ed from the counter-flow concentration units which mentioned in Article I. The e ciency of the splitting and recombination (SAR) micromixer was examined by theoretical methods, including finite element method and verifi ed by measurement results. Numerical results show that micromixer with ellipse-like micropillars have a well mixing status when its mixing effi ciency is higher than 80% as Re 6 1. Article III presented that the e ciency of the SAR micromixer for cell lysis. Some bacteria, especially gram-positive, may be diffi cult to lyse with conventional lysis bu er. If the cells are not properly lysed, the quality of the analysis results might suff er. With a splitting and recombination concept, homogeneous mixing can be obtained in short distance. Hence, the quality of the sample after lysis for further process (Nucleic Acid Purifi cation, Nucleic Acid Sequence Based Ampli fication) is also improved. The treatment in the SAR micromixer is comparable lysis by long ultrasound exposure. Hence, SAR micromixer proved to be a good alternative method for cell lysis. Moreover, SAR micromixer has the advantage that it can easily be integrated into an automatic system for lysis and sample treatment. Article IV investigated the mixing performance at the outlet of SAR micromixer. The outlet channel of SAR micromixer was split into four sub-channels. Absorbance testing was used to implement to evaluate the outlet concentration of four subchannels. The homogeneous of fluids are varied with the inlet velocities. Article V presented the optimized fabrication process of the template of extremely long microneedles for blood extraction. Backside lithography with a UVlight source was employed to build the high aspect ratio SU-8-based microneedle template. Some major challenges on fabrication process were also shown and discussed in this article. Article VI covers a total process chain from design, fabrication to performance evaluation of the hollow microneedle design. The contribution of this article is a highly applicable theoretical model for the microneedle geometry. The proposed model has been developed to predict the fracture forces. A good agreement was observed between the results obtained from analytical solution and practical measurements of fracture force

OPTIMASI MIKROMIXER BERBASIS RINTANGAN KOCH SNOWFLAKES FRACTAL UNTUK APLIKASI LAB ON CHIP

Perkembangan sistem mikromixer telah menarik minat khusus sejalan dengan perkembangan perangkat Lab on Chip (LoC) dengan upaya miniaturisasi dan portable. Penelitian ini bertujuan: 1) Mengetahui pengaruh struktur rintangan Koch snowflakes fractal terhadap efisiensi pencampuran, 2) Mengetahui pengaruh struktur saluran masuk T-vortex terhadap efisiensi pencampuran, dan 3) Mengetahui pengaruh bilangan Reynolds (0,05-100) terhadap efisiensi pencampuran. Penelitian ini menggunakan metode simulasi pada perangkat lunak COMSOL Multiphysics 4.6. Desain yang digunakan dalam simulasi ini terdiri dari empat struktur yang berbeda yaitu pada struktur rintangan Secondary Snowflakes Fractal (SSF), Tertiary Snowflakes Fractal (TSF), Rounding Secondary Snowflakes Fractal (RSSF), dan Rounding Tertiary Snowflakes Fractal (RTSF). Masing-masing struktur diuji berdasarkan sudut rintangan yaitu 15°, 30°, 45°, 315°, 330°, dan 345°, serta kedalaman rintangannya yaitu dari rentang 0,01-0,19 mm. Kemudian struktur SSF, TSF, RSSF, dan RTSF dikombinasikan dengan struktur saluran masuk T-vortex untuk lebih meningkatkan efisiensi pencampurannya. Struktur geometri tersebut memiliki panjang, lebar dan tinggi 5 mm x 0,3 mm x 0,2 mm. penelitian ini dilakukan untuk mengoptimalkan struktur mikromixer berbasis rintangan dalam aplikasi LoC. Hasil penelitian menunjukkan bahwa mikromixer dengan struktur rintangan Tertiary Snowflakes Fractal (TSF) pada sudut 30° dan kedalaman 0,17 mm, serta saluran utama T-vortex menghasilkan performa yang lebih baik yaitu sebesar >98% pada Re rendah (0,05-100). Hasil tersebut dapat diasumsikan bahwa cairan telah tercampur secara homogen. Dengan tercapainya parameter dimensi panjang saluran 80% yang beroperasi pada Re rendah, maka desain mikromixer ini sesuai dengan konsep divais dalam sistem LoC yang dapat diaplikasikan pada bidang analisis kimia. The development of micromixer systems has attracted special interest, in line the development of Lab on Chip (LoC) devices with efforts to miniaturization and portable. This study aims to: 1) determine the effect of the Koch snowflakes fractal barrier structure on the mixing efficiency, 2) determine the effect of T-vortex inlet structure on mixing efficiency, and 3) determine the effect of Reynolds number (0.05-100) on mixing efficiency. This study used the simulation method on the COMSOL Multiphysics 4.6 software. The design used in this simulation consists of four different structures, namely Secondary Snowflakes Fractal (SSF), Tertiary Snowflakes Fractal (TSF), Rounding Secondary Snowflakes Fractal (RSSF), dan Rounding Tertiary Snowflakes Fractal (RTSF). Each structure was tested based on the angle of obstruction, namely 15°, 30°, 45°, 315°, 330°, and 345°, and the depth of the obstacle is from 0.01-0.19 mm. Then the SSF, TSF, RSSF, and RTSF structures are combined with the T-vortex inlet structure to further improve their mixing efficiency. The geometry structure has a length, width and height of 5 mm x 0.3 mm x 0.2 mm. This research was conducted to optimize the barrier-based micromixer structure in LoC applications. The results showed that the micromixer with the obstacle structure Tertiary Snowflakes Fractal (TSF) at an angle of 30° and a depth of 0.17 mm, as well as a T-vortex main channel produced better performance of >98% at low Re (0.05- 100). These results can be assumed that the liquid has been mixed homogeneously. With the achievement of the channel length dimension parameter is 80% operating at low Re, the design of this micromixer is following the concept of devices in the LoC system that can be applied to the field of chemical analysis

DESIGN AND MIXING PERFORMANCE OF PASSIVE MICROMIXERS: A CRITICAL REVIEW

This study extracts and reports notable findings on passive micromixers by conducting an exhaustive review of designs, their features, and mixing performance. The study has covered the relevant articles on passive micromixers published from 2010 to 2020. The analysis of filtered and selected articles sums up passive micromixers into four categories: designed inlets, designed mixing-channel, lamination-based, and flow obstacles-based. The prominent mixing channel categories identified in the study are split-and-recombine (SAR), convergent-divergent (C-D), and mixed (SAR, C-D, and others). Moreover, differences in mixing channel designs, number of inlets, and evaluation methods have been used in comparing the mixing performance of passive micromixers. The SAR and the obstacles-based micromixers were found to outperform the others. The designs covered in the present review show significant improvements in the mixing index. However, these studies were conducted in an isolated environment, and most of the time, their fabrication and device integration issues were ignored. The assortment and critical analysis of micromixers based on their design features and flow parameters will be helpful to researchers interested in designing new passive micromixers for microfluidic applications

Micro/Nano-Chip Electrokinetics

Micro/nanofluidic chips have found increasing applications in the analysis of chemical and biological samples over the past two decades. Electrokinetics has become the method of choice in these micro/nano-chips for transporting, manipulating and sensing ions, (bio)molecules, fluids and (bio)particles, etc., due to the high maneuverability, scalability, sensitivity, and integrability. The involved phenomena, which cover electroosmosis, electrophoresis, dielectrophoresis, electrohydrodynamics, electrothermal flow, diffusioosmosis, diffusiophoresis, streaming potential, current, etc., arise from either the inherent or the induced surface charge on the solid-liquid interface under DC and/or AC electric fields. To review the state-of-the-art of micro/nanochip electrokinetics, we welcome, in this Special Issue of Micromachines, all original research or review articles on the fundamentals and applications of the variety of electrokinetic phenomena in both microfluidic and nanofluidic devices

Analysis, Design and Fabrication of Micromixers

This book includes an editorial and 12 research papers on micromixers collected from the Special Issue published in Micromachines. The topics of the papers are focused on the design of micromixers, their fabrication, and their analysis. Some of them proposed novel micromixer designs. Most of them deal with passive micromixers, but two papers report studies on electrokinetic micromixers. Fully three-dimensional (3D) micromixers were investigated in some cases. One of the papers applied optimization techniques to the design of a 3D micromixer. A review paper is also included and reports a review of recently developed passive micromixers and a comparative analysis of 10 typical micromixers

Design and development of a microfluidic platform for use with colorimetric gold nanoprobe assays

Due to the importance and wide applications of the DNA analysis, there is a need to make genetic analysis more available and more affordable. As such, the aim of this PhD thesis is to optimize a colorimetric DNA biosensor based on gold nanoprobes developed in CEMOP by reducing its price and the needed volume of solution without compromising the device sensitivity and reliability, towards the point of care use. Firstly, the price of the biosensor was decreased by replacing the silicon photodetector by a low cost, solution processed TiO2 photodetector. To further reduce the photodetector price, a novel fabrication method was developed: a cost-effective inkjet printing technology that enabled to increase TiO2 surface area. Secondly, the DNA biosensor was optimized by means of microfluidics that offer advantages of miniaturization, much lower sample/reagents consumption, enhanced system performance and functionality by integrating different components. In the developed microfluidic platform, the optical path length was extended by detecting along the channel and the light was transmitted by optical fibres enabling to guide the light very close to the analysed solution. Microfluidic chip of high aspect ratio (~13), smooth and nearly vertical sidewalls was fabricated in PDMS using a SU-8 mould for patterning. The platform coupled to the gold nanoprobe assay enabled detection of Mycobacterium tuberculosis using 3 8l on DNA solution, i.e. 20 times less than in the previous state-of-the-art. Subsequently, the bio-microfluidic platform was optimized in terms of cost, electrical signal processing and sensitivity to colour variation, yielding 160% improvement of colorimetric AuNPs analysis. Planar microlenses were incorporated to converge light into the sample and then to the output fibre core increasing 6 times the signal-to-losses ratio. The optimized platform enabled detection of single nucleotide polymorphism related with obesity risk (FTO) using target DNA concentration below the limit of detection of the conventionally used microplate reader (i.e. 15 ng/μl) with 10 times lower solution volume (3 μl). The combination of the unique optical properties of gold nanoprobes with microfluidic platform resulted in sensitive and accurate sensor for single nucleotide polymorphism detection operating using small volumes of solutions and without the need for substrate functionalization or sophisticated instrumentation. Simultaneously, to enable on chip reagents mixing, a PDMS micromixer was developed and optimized for the highest efficiency, low pressure drop and short mixing length. The optimized device shows 80% of mixing efficiency at Re = 0.1 in 2.5 mm long mixer with the pressure drop of 6 Pa, satisfying requirements for the application in the microfluidic platform for DNA analysis.Portuguese Science Foundation - (SFRH/BD/44258/2008), “SMART-EC” projec

Microfluidic system for cell separation and deformation assessment by using passive methods

Tese de doutoramento em Biomedical EngineeringOs sistemas microfluídicos têm sido usados com sucesso em muitas aplicações biomédicas. As principais vantagens destes sistemas consistem na utilização de volumes de amostras reduzidos e com tempos de ensaios curtos. Além disso, os sistemas microfluídicos possibilitam a execução de várias tarefas em paralelo numa única plataforma microfluídica, como por exemplo a separação e medição da deformabilidade de células/partículas. Em dispositivos microfluídicos, existem dois métodos principais para separar células: métodos passivos, baseados em microestruturas e escoamentos laminares, e métodos ativos, baseados em campos de forças externos. Muitos estudos têm sido realizados com métodos passivos, pois estes não necessitam de forças externas. Nesta tese serão apresentadas diferentes geometrias passivas para um dispositivo microfluídico, constituído por vários filtros de fluxo cruzado e multiníveis com o intuito de separar células/partículas em função do seu tamanho. Outra característica importante é a implementação de microcanais hiperbólicos a montante das saídas por forma a criar um escoamento extensional homogéneo e consequentemente medir a deformabilidade das células de forma controlada. Após a separação e avaliação da deformação, a quantidade de glóbulos vermelhos será quantificada por um método de espectrofotometria. Os resultados indicam que várias geometrias mostraram uma boa taxa de separação, confirmada pelas medidas de camada livre de células e pela espectrofotometria. Verificou-se também que os sistemas microfluídicos testados são capazes de separar amostras patológicas de sangue, demostrando assim o seu potencial em realizar simultaneamente a separação e deformação de células patológicas, como por exemplo células provenientes de pacientes diagnosticados com malária e/ou diabetes.Microfluidic systems have been successfully used at many biomedical applications. Their great advantages allow working with minimal sample volumes and with short assays times. Additionally, microfluidic systems allow parallel operations in a single microfluidic platform such as separation and measurement of single cell/particles deformability. In microfluidic devices, there are two main methods for cells separation: passive methods, based on microstructures and laminar flow, and active methods, based on external force fields. Many studies have been made using passive methods because they do not require external forces. In this thesis it will be presented different geometrical passive approaches for a microfluidic device, that will have crossflow filters and multilevel steps that will separate the cells/particles by their size. Another important feature is the implementation of hyperbolic microchannels upstream the outlets in order to create a homogeneous extensional flow and consequently to measure the cells deformability in a controlled way. After the separation and deformation assessment, the amount of RBCs will be quantified by a spectrophotometry method. The results indicate that several geometries have shown a good separation rate, confirmed by the cell free layer and spectrophotometry measurements. It was also verified that the tested microfluidic systems are able to separate pathological blood samples, showing its potential to perform simultaneously separation and deformation assessments of blood diseases, such as malaria and diabetes.I want to acknowledge the financial support provided by scholarship SFRH/BD/99696/2014 from FCT (Science and Technology Foundation), COMPETE 2020, Portugal 2020 and POCH, that allow the successful development of this PhD project

Development and Characterization of Microencapsulation Systems for Bioactive Ingredients of Interest in the Development of Functional Foods

Tesis por compendioThe aim of the present work was to design and characterize novel encapsulation structures of interest in the development of functional foods. For this purpose, various biopolymer-based microencapsulation structures were obtained through different processing technologies, with an emphasis on electrospraying as an advantageous alternative to conventional microencapsulation techniques. Firstly, novel microencapsulation structures were produced from aqueous solutions and in mild conditions by electrospraying, using different biopolymers as encapsulation matrices. For this purpose, the processing conditions were optimized and the relationship between the feed solution properties and the morphology of the electrosprayed materials was studied. The developed microstructures were then used to microencapsulate model bioactive ingredients with different properties, including hydrophilic molecules, hydrophobic compounds and probiotic microorganisms. For the hydrophobic ingredients, different strategies were evaluated in order to disperse them within the aqueous biopolymer solutions, such as the preparation of emulsions and liposome dispersions prior to electrospraying. An in-line setup for the continuous mixing of liposomes with the biopolymer and their subsequent hybrid capsule formation was also developed by combining microfluidic and electrospraying technologies. For the probiotic microorganisms, the convenience of preparing the feed suspensions from fresh culture or freeze-dried bacteria, as well as the impact of adding a surfactant and a prebiotic carbohydrate to the formulation, were also evaluated. The performance of the proposed encapsulation systems was evaluated in terms of microencapsulation efficiency, stabilization of the bioactive ingredients against degradation under detrimental conditions and/or their impact on the bioaccessibility of the microencapsulated ingredients after in-vitro digestion. Spray-drying was also used to microencapsulate some of the bioactive ingredients, in order to compare the results obtained through electrospraying with a more conventional encapsulation technique and using different encapsulation matrices. Additionally, a novel concept of bio-inspired encapsulation was proposed in this thesis: the potential of intact plant cells isolated from potato tubers to bind phenolic compounds was explored, and the impact of starch gelatinization on the loading capacity of these proposed encapsulation vehicles was also assessed. Finally, the impact of microencapsulation in real food systems was also studied. Yoghurts and biscuits were enriched with a peptide hydrolysate and a green tea extract, respectively, and the stabilization effect of the protective matrices during food manufacturing was assessed. The consumers' acceptability of the enriched biscuits was also studied.El objetivo de este trabajo fue el diseño y caracterización de nuevas estructuras de encapsulación de interés en el desarrollo de alimentos funcionales. Para ello, se obtuvieron distintas microestructuras de encapsulación biopoliméricas utilizando diferentes tecnologías de procesado, con especial hincapié en el electroesprayado como alternativa ventajosa a las técnicas de microencapsulación convencionales. En primer lugar, se desarrollaron nuevas microestructuras de encapsulación a partir de disoluciones acuosas y en condiciones suaves mediante la técnica de electroesprayado, utilizando diferentes biopolímeros como matrices de encapsulación. Para ello, se optimizaron las condiciones de procesado y se estudió la relación existente entre las propiedades de las disoluciones de partida y la morfología de los materiales electroesprayados obtenidos a partir de ellas. Posteriormente, se utilizaron las estructuras desarrolladas para microencapsular ingredientes bioactivos modelo con diferentes propiedades, incluyendo moléculas hidrofílicas, compuestos hidrofóbicos y microorganismos probióticos. En el caso de los ingredientes hidrofóbicos, se evaluaron diferentes estrategias para dispersarlos en las disoluciones poliméricas acuosas, como la preparación de emulsiones y de liposomas para su posterior procesado mediante electroesprayado. También se desarrolló un proceso en línea para mezclar los liposomas con el biopolímero y electroesprayarlos en continuo, combinando las tecnologías de microfluídica y electroesprayado. En el caso de los microorganismos probióticos, se evaluó también la conveniencia de preparar las suspensiones bacterianas a partir de cultivo fresco o de liófilos, así como el impacto de añadir un surfactante y un carbohidrato prebiótico a la formulación. El comportamiento de los sistemas de encapsulación propuestos se evaluó en cuanto a eficiencia de encapsulación, estabilización de los ingredientes bioactivos frente a condiciones de estrés y/o impacto sobre la bioaccesibilidad de dichos ingredientes tras un proceso de digestión in-vitro. También se utilizó la técnica de secado por pulverización para microencapsular alguno de los ingredientes bioactivos, con el fin de comparar los resultados obtenidos mediante electroesprayado con los de una técnica de encapsulación convencional, y utilizando diferentes matrices de encapsulación. Además, en esta tesis se propone un nuevo concepto de encapsulación bio-inspirada, basada en el potencial de células vegetales de patata intactas para unirse a compuestos fenólicos. Asimismo, se evaluó el efecto de la gelatinización previa del almidón presente en las células en la capacidad de carga de estos potenciales vehículos de encapsulación. Por último, se estudió el impacto de la microencapsulación en alimentos reales. Se enriquecieron yogures y galletas con un hidrolizado de péptidos y un extracto de té, respectivamente, y se estudió el efecto estabilizador de las microcápsulas durante el procesado de estos alimentos. También se estudió la aceptabilidad por parte de los consumidores de estas galletas enriquecidas.L'objectiu d'aquest treball va ser el disseny i caracterització de noves estructures d'encapsulació d'interès en el desenvolupament d'aliments funcionals. Amb aquesta finalitat, es van obtenir diferents microestructures d'encapsulació biopolimèriques utilitzant diferents tecnologies de processat, amb especial èmfasi en el electrosprayat com a alternativa avantatjosa a les tècniques de microencapsulació convencionals. En primer lloc, es van desenvolupar noves microestructures d'encapsulació a partir de dissolucions aquoses i en condicions suaus mitjançant la tècnica de electrosprayat, utilitzant diferents biopolímers com a matrius d'encapsulació. Per a això, es van optimitzar les condicions de processament i es va estudiar la relació existent entre les propietats de les dissolucions de partida i la morfologia dels materials electrosprayats obtinguts a partir d'elles. Posteriorment, es van utilitzar les estructures desenvolupades per microencapsular ingredients bioactius model amb diferents propietats, incloent molècules hidròfiles, compostos hidrofòbics i microorganismes probiòtics. En el cas dels ingredients hidrofòbics, es van avaluar diferents estratègies per a dispersar-los en les dissolucions polimèriques aquoses, com la preparació d'emulsions i de liposomes per al seu posterior processat mitjançant electrosprayat. També es va desenvolupar un procés en línia per a mesclar els liposomes amb el biopolímer i electrosprayar-los en continu, combinant les tecnologies de microfluídica i electrosprayat. En el cas dels microorganismes probiòtics, es va avaluar també la conveniència de preparar les suspensions bacterianes a partir de cultiu fresc o de liòfils, així com l'impacte d'afegir un surfactant i un carbohidrat prebiòtic a la formulació. El comportament dels sistemes d'encapsulació proposats es va avaluar respecte a eficiència d'encapsulació, estabilització dels ingredients bioactius front a condicions d'estrès i / o l'impacte sobre la bioaccesibilitat d'aquests ingredients després de la seva digestió in-vitro. També es va utilitzar la tècnica d'assecat per polvorització per microencapsular algun dels ingredients bioactius, per tal de comparar els resultats obtinguts mitjançant electrosprayat amb els d'una tècnica d'encapsulació convencional, i utilitzant diferents matrius d'encapsulació. A més, en aquesta tesi es proposa un nou concepte d'encapsulació bio-inspirada, basada en el potencial de cèllules vegetals de creïlles intactes per unir-se a compostos fenòlics. Així mateix, es va avaluar l'efecte de la gelatinització prèvia del seu midó en la capacitat de càrrega d'aquests potencials vehicles d'encapsulació. Finalment, es va estudiar l'impacte de la microencapsulació en aliments reals. Es van enriquir iogurts i galetes amb un hidrolitzat de pèptids i un extracte de té, respectivament, i es va estudiar l'efecte estabilitzador de les microcàpsules durant el processat dels aliments. També es va estudiar l'acceptabilitat per part dels consumidors d'aquestes galetes enriquides.Gómez Gómez-Mascaraque, L. (2017). Development and Characterization of Microencapsulation Systems for Bioactive Ingredients of Interest in the Development of Functional Foods [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/93344TESISCompendi

Microdevices and Microsystems for Cell Manipulation

Microfabricated devices and systems capable of micromanipulation are well-suited for the manipulation of cells. These technologies are capable of a variety of functions, including cell trapping, cell sorting, cell culturing, and cell surgery, often at single-cell or sub-cellular resolution. These functionalities are achieved through a variety of mechanisms, including mechanical, electrical, magnetic, optical, and thermal forces. The operations that these microdevices and microsystems enable are relevant to many areas of biomedical research, including tissue engineering, cellular therapeutics, drug discovery, and diagnostics. This Special Issue will highlight recent advances in the field of cellular manipulation. Technologies capable of parallel single-cell manipulation are of special interest

Biodiesel synthesis in microchannels

Orientador: Osvaldir Pereira TarantoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia QuímicaResumo: Essa tese investigou numérica e experimentalmente o processo de síntese e purificação do biodiesel em microcanais. A síntese de biodiesel foi realizada através da reação de óleo vegetal e álcool na presença de catalisador básico. Essa reação que ocorre com excesso de álcool para deslocar o equilíbrio da reação para os produtos, produz o biodiesel e o coproduto glicerol. Assim, além da reação de síntese, o processo de produção do biodiesel envolve a remoção do álcool não reagido e do glicerol. Na literatura são encontrados estudos que avaliam a aplicação de microdispositivos na síntese de biodiesel, porém, poucos trabalhos aplicam as características da microescala na purificação desse combustível (remoção do álcool em excesso e glicerol) e técnicas de modelagem e simulação que podem otimizar o processo de síntese e os microdispositivos utilizados. A síntese foi inicialmente avaliada numericamente para o óleo de Pinhão Manso e etanol em micromisturadores com diferentes geometrias e os resultados mostraram que a reação entre os reagentes é controlada pelos processos de mistura e cinética de reação e que o tempo de residência desempenha um papel importante na conversão do óleo, sendo demonstrado que a conversão é mais afetada pelo tempo de residência do que pelo tipo de geometria. Em seguida foi investigado a síntese de biodiesel a partir do óleo de girassol experimentalmente e numericamente. A máxima porcentagem dos ésteres etílicos (FAEE) obtida para o reator batelada convencional e para o microreator foi de 94,06% e 95,80%, respectivamente. Foi demonstrado que os parâmetros rendimento e seletividade representam melhor a simulação do processo de transesterificação do óleo de girassol. Com esses resultados foi possível desenvolver microdispositivos mais eficientes para a síntese de biodiesel. Os microdispositivos com obstruções circulares e com elementos estáticos mostraram experimentalmente elevadas FAEE com valores acima de 99%. Após os ensaios numéricos e experimentais de síntese foi explorado a purificação do biodiesel em microcanais. Os resultados da remoção do álcool mostraram que a temperatura influenciou positivamente a evaporação/separação do álcool, com um aumento dessa variável, a separação é maior. As variáveis vazão dos fluidos e razão molar possuem um efeito contrário. A remoção do glicerol do biodiesel em microcanais é influenciada estatisticamente pelo tempo de residência e a interação entre o tempo de residência e fração volumétrica dos fluidos glicerina e biodieselAbstract: This thesis investigated numerically and experimentally the process of synthesis and purification of biodiesel in microchannels. The biodiesel synthesis was performed by reaction of vegetable oil and alcohol in the presence of basic catalyst. This reaction occurs with excess alcohol to displace the equilibrium of the reaction towards the products, produce biodiesel and glycerol. Thus, besides the synthesis reaction, the biodiesel production process involves the remotion of the unreacted alcohol and glycerol. No studies were found to apply the microscale features in purification of the biofuel (removal of alcohol in excess and glycerol), or the application of modeling techniques and simulation that can optimize the synthesis process and the microdevices used. The synthesis was initially evaluated numerically for the Jatropha curcas oil and ethanol in micromixers with different geometries for the microchannels and the results showed that the reaction between the reactants is controlled by the mixing and the reaction kinetics and residence time plays a key role in oil conversion. It was demonstrated that the conversion is more affected by the residence time that the geometry type. It was then investigated the synthesis of biodiesel from sunflower oil experimentally and numerically. The maximum percentage of ethyl esters (FAEE) obtained for the batch reactor and the microreactor was 94.06% and 95.80%, respectively. It was shown that the yield and selectivity parameters better represent the simulation of sunflower oil transesterification process. With these results it was possible to develop more efficient microdevices for biodiesel synthesis. The microdevices with circular obstructions and static elements showed high FAEE with values above 99%. After the synthesis was explored the biodiesel purification in microchannels. The results of the removal of alcohol showed that the temperature influenced positively evaporation/separation of alcohol, an increase of this variable, the separation is greater and the variable flow of fluids and molar ratio has the opposite effect. The biodiesel glycerol removal of microchannels is statistically affected by residence time, and the interaction between the residence time and volume fraction of glycerol and biodieselDoutoradoEngenharia de ProcessosDoutor em Engenharia QuímicaCAPE