Selective Resistive Sintering: A Novel Additive Manufacturing Process

Selective laser sintering (SLS) is one of the most popular 3D printing methods that uses a laser to pattern energy and selectively sinter powder particles to build 3D geometries. However, this printing method is plagued by slow printing speeds, high power consumption, difficulty to scale, and high overhead expense. In this research, a new 3D printing method is proposed to overcome these limitations of SLS. Instead of using a laser to pattern energy, this new method, termed selective resistive sintering (SRS), uses an array of microheaters to pattern heat for selectively sintering materials. Using microheaters offers significant power savings, significantly reduced overhead cost, and increased printing speed scalability. The objective of this thesis is to obtain a proof of concept of this new method. To achieve this objective, we first designed a microheater to operate at temperatures of 600⁰C, with a thermal response time of ~1 ms, and even heat distribution. A packaging device with electrical interconnects was also designed, fabricated, and assembled with necessary electrical components. Finally, a z-stage was designed to control the airgap between the printhead and the powder particles. The whole system was tested using two different scenarios. Simulations were also conducted to determine the feasibility of the printing method. We were able to successfully operate the fabricated microheater array at a power consumption of 1.1W providing significant power savings over lasers. Experimental proof of concept was unsuccessful due to the lack of precise control of the experimental conditions, but simulation results suggested that selectivity sintering nanoparticles with the microheater array was a viable process. Based on our current results that the microheater can be operated at ~1ms timescale to sinter powder particles, it is believed this new process can potentially be significantly quicker than selective laser sintering by increasing the number of microheater elements in the array. The low cost of a microheater array printhead will also make this new process affordable. This thesis presented a pioneering study on the feasibility of the proposed SRS process, which could potentially enable the development of a much more affordable and efficient alternative to SLS

Lab-on-PCB Devices

Lab-on-PCB devices can be considered an emerging technology. In fact, most of the contributions have been published during the last 5 years. It is mainly focussed on both biomedical and electronic applications. The book includes an interesting guide for using the different layers of the Printed Circuit Boards for developing new devices; guidelines for fabricating PCB-based electrochemical biosensors, and an overview of fluid manipulation devices fabricated using Printed Circuit Boards. In addition, current PCB-based devices are reported, and studies for several aspects of research and development of lab-on-PCB devices are described

Microheater: material, design, fabrication, temperature control, and applications—a role in COVID‑19

Heating plays a vital role in science, engineering, mining, and space, where heating can be achieved via electrical, induction, infrared, or microwave radiation. For fast switching and continuous applications, hotplate or Peltier elements can be employed. However, due to bulkiness, they are inefective for portable applications or operation at remote locations. Miniaturization of heaters reduces power consumption and bulkiness, enhances the thermal response, and integrates with several sensors or microfuidic chips. The microheater has a thickness of~100 nm to~100 μm and ofers a temperature range up to 1900℃ with precise control. In recent years, due to the escalating demand for fexible electronics, thin-flm microheaters have emerged as an imperative research area. This review provides an overview of recent advancements in microheater as well as analyses diferent microheater designs, materials, fabrication, and temperature control. In addition, the applications of microheaters in gas sensing, biological, and electrical and mechanical sectors are emphasized. Moreover, the maximum temperature, voltage, power consumption, response time, and heating rate of each microheater are tabulated. Finally, we addressed the specifc key considerations for designing and fabricating a microheater as well as the importance of microheater integration in COVID-19 diagnostic kits. This review thereby provides general guidelines to researchers to integrate microheater in micro-electromechanical systems (MEMS), which may pave the way for developing rapid and large-scale SARS-CoV-2 diagnostic kits in resource-constrained clinical or home-based environments

MEMS-based Lab-on-chip platform with integrated 3D and planar microelectrodes for organotypic and cell cultures

La presente tesis doctoral se centra en el desarrollo y la validación de plataformas lab on chip (LOC) para su aplicación en el campo de la Biología, la Medicina y la Biomedicina, particularmente relacionados con el cultivo de células y tejidos, así como su tratamiento mediante electroestimulación y su actividad eléctrica. Actualmente, las investigaciones centradas en el desarrollo de LOCs han experimentado un crecimiento considerable, gracias, en gran medida, a la versatilidad que ofrecen. Dicha versatilidad se traduce en numerosas aplicaciones, de las cuales, aquellas relacionadas con la Biología y la Medicina, están alcanzando especial relevancia. La integración de sensores, actuadores, circuitos microfluídicos y circuitos electrónicos en la misma plataforma, permite fabricar sistemas con múltiples aplicaciones. Esta tesis se centra fundamentalmente en el desarrollo de plataformas para el cultivo in vitro de tejidos y células, así como para la monitorización y la interacción con dicho cultivo. Los cultivos in vitro resultan de vital importancia para realizar estudios en células o tejidos, experimentar con medicamentos o estudiar su proliferación y morfología. De esta manera, se cubriría la creciente necesidad de encontrar una alternativa para replicar modelos humanos de enfermedades in vitro para poder desarrollar nuevos fármacos y avanzar en la medicina personalizada. Por tanto, la posibilidad de realizar cultivos de media o larga duración en plataformas que no precisen de un equipamiento costoso como las incubadoras de CO2 y que puedan ser monitorizadas mediante aplicaciones ópticas, supone un salto cualitativo en el desarrollo de los cultivos in vitro. En este contexto, se presenta el trabajo relacionado con esta tesis que ha sido desarrollada dentro del grupo de Microsistemas de la Escuela Superior de Ingeniería de la Universidad de Sevilla. La tesis está estructurada de manera que a lo largo de este escrito se da respuesta a los distintos aspectos anteriormente descritos. En primer lugar, se hace una breve introducción a la tecnología MEMS y a los principios básicos de la microfluídica. Dado que este trabajo se ha desarrollado en un ambiente multidisciplinar, esta sección resulta necesaria para dar una visión general a aquellos no familiarizados con esta disciplina. Tras esa introducción se realiza una descripción del estado del arte en el que se encuadra este trabajo, incluyendo los sistemas LoCs, y sus principales aplicaciones en el campo de la Biología, Medicina y Biomedicina, prestando especial atención a las aplicaciones de los LoCs relacionadas con cultivos organotípicos y de células. Tras la introducción y el estado del arte en el que se enmarca la tesis, se explican los resultados obtenidos durante este trabajo. Durante la primera parte, se describe el desarrollo, fabricación y caracterización de un sistema autónomo para el cultivo y electroestimulación de tejidos que integra un lab on PCB (LOP) formado por un array de microelectrodos en 3D (MEA) formado por hilos de oro de 25 µm en sustrato transparente, sensores y actuadores, junto con una plataforma microfluídica fabricada en metacrilato (PMMA) y polidimetilsiloxano (PDMS). El LOP permite mantener las condiciones de temperatura idóneas para llevar a cabo cultivos de media-larga duración sin necesidad de usar incubadoras deCO2 , así como su seguimiento de forma continua a través de un microscopio, gracias al uso de materiales transparentes. Este sistema también incluye una electrónica suplementaria y un programa que permite la monitorización del sistema y la electrostimulación de la muestra biológica. Tras explicar detalladamente el diseño y el novedoso proceso de fabricación del LOP, se presentan los resultados experimentales. En primer lugar, se ha demostrado que es posible desarrollar cultivos organotípicos de retinas de ratón durante más de 7 días, obteniendo resultados muy similares a los conseguidos para las mismas muestras biológicas, pero mediante métodos de cultivo tradicionales. Además, se ha logrado la neuro-protección mediante la electroestimulación de retinas de ratón con la enfermedad de la retinosis pigmentaria, logrando de esta manera ralentizar la degeneración de la muestra debido a la enfermedad. Otra de las aplicaciones que se quiere conseguir con el desarrollo del LOP anteriormente descrito se centra en la adquisición de señales eléctricas procedentes de las muestras biológicas cultivadas en el dispositivo, así como extrapolar su uso a cultivos celulares. Para la adquisición de señales procedentes del cultivo, la impedancia de los electrodos fabricados con hilos de oro de 25 µm ha resultado ser demasiado alta como para discernir entre el ruido base y la actividad eléctrica del cultivo. Por ello, la segunda parte de esta tesis doctoral se centra en la mejora de la MEA para la adquisición de actividad eléctrica. Dado el objetivo marcado en esta segunda parte, durante esta tesis se ha realizado una estancia en la Universidad de Bath. En dicha estancia, se ha caracterizado la actividad eléctrica de células del cáncer de próstata (PC-3), que fueron cultivadas en chips de silicio con electrodos de oro. La experiencia obtenida durante la estancia ha permitido avanzar en el desarrollo y la fabricación de nuevas MEAs para la adquisción de señales eléctricas de cultivos celulares. La primera aproximación para mejorar la MEA se ha realizado sobre PCB. Se trata de un dispositivo compuesto por pilares de oro en 3D fabricados mediante la técnica de Resumen XXV electroplating. Estos electrodos tienen 100 µm de diámetro y una altura de 25 µm que aseguran el contacto en el caso de cultivos de tejidos. Se ha demostrado una mejora significativa, traducida tanto en una impedancia más baja, como en una línea base de ruido menor con respecto a la MEA con hilos de oro. Asimismo, se han obtenido patrones de actividad eléctrica en las células PC-3 muy similares a los obtenidos con el chip de silicio y oro empleado en la estancia. Como mejora de la MEA 3D se ha cambiado el sustrato por otro transparente, como vidrio o PMMA, para permitir su uso en aplicaciones ópticas. Dichas MEAs integran electrodos planares fabricados mediante la técnica de sputtering de oro sobre su superficie. Estas MEAs están en una fase preliminar de desarrollo, y se está probando en primer lugar su biocompatibilidad y viabilidad para el desarrollo de cultivos celulares. Para finalizar, se exponen las conclusiones de esta tesis doctoral, entre las que destacan: el proceso de fabricación del LOP con electrodos de oro y la aplicación del sistema completo para desarrollar cultivos organotípicos, monitorizarlos y aplicar electroestimulación, logrando la neuro-protección de retinas de ratón con la retinosis pigmentaria; la transición hacia el desarrollo de una plataforma para cultivos celulares mejorando la MEA y su fabricación usando diferentes sustratos; la caracterización de la actividad eléctrica de las células PC-3. También se incluyen las líneas de investigación abiertas para continuar lo que se ha empezado en esta tesis doctoral. Para facilitar la comprensión del lector, se adjuntan los apéndices complementarios a esta tesis doctoral.The presented thesis is focused on the development and validation of lab on chip (LOC) platforms for their application on Biology, Medicine and Biomedicine, particularly those related with cells and tissues cultures, as well as their treatment through electrostimulation and their electrical behavior. Nowadays, research works focused on the development of LOCs have significantly increased, mostly thanks to its high versatility, which involves countless applications. Among all this applications, those related with Biology and Medicine are becoming more and more important. The integration of sensors, actuators, microfluidic circuits and electronic circuits in the same platform allows the fabrication of systems with lots of applications. This thesis is focused on the development of platforms for in vitro cultures of cells and tissues, to monitor their behavior and interact with the biological samples. The importance of in vitro cultures lies on the study of cells and tissues proliferation and morphology or performing drug delivery experiments. In this respect, through LOC technologies, it would be possible to model human diseases in vitro, in order to improve the development of new drugs and advance personalized medicine. Thus, the possibility of carrying out medium-long term cultures on platforms without the need of any expensive equipment, such as CO2 incubators, with software and monitoring, implies a qualitative step forward in the development of in vitro cultures. Within this framework, the work related to this thesis is presented. This PhD has been undertaken in the Microsystem group of the High School Engineering of the University of Seville. The structure of this thesis is organized in such a way that, all along the text, the different aspects previously described are explained in detail. Firstly, a brief introduction about MEMS technology and the basic principles of Microfluidics is presented. Due to this work has been developed in a multidisciplinary environment, this section becomes necessary in order to give a wide view to those non XXVII XXVIII Abstract directly familiarized with these fields. Subsequently, a description of the state of the art is presented, including LOC systems and their applications in Biology, Medicine and Biomedicine, taking special attention to those applications related to organotypic and cell cultures. After the introduction and the state of the art of the framework of this thesis, the results obtained are presented. In the first part of this PhD, the development, fabrication and characterization of the autonomous system for culture and electrostimulation of tissues is described. This system includes a lab on PCB (LOP) composed of a 3D microelectrode array (MEA), with gold wires of 25 µm on transparent substrate, sensors and actuators, together with a microfluidic platform made of PMMA and PDMS. This LOP allows to maintain the appropriate temperature conditions to carry out medium-long term cultures without using a CO2 incubator, as well as its continuous monitoring through an inverted microscope, thanks to the transparent materials used for its fabrication. This system is connected to an external electronic circuit and a software to control the whole system, including the electrostimulation of the biological sample. After explaining the design and the innovative fabrication process of the LOP, the experimental results are presented. Firstly, it has been demonstrated the suitability of this system to perform organotypic cultures of mice retinas for longer than 7 days, obtaining similar results to the same samples, but cultured through traditional methods. In addition, it has been provided neuroprotection to mice retinal explants with the retinitis pigmentosa (RP) disease through the electrostimulation of the samples, being able to slowdown the degeneration of the retinas caused by RP

INVESTIGATION OF PYROELECTRIC EFFECT GENERATED BY LITHIUM NIOBATE CRYSTALS INDUCED BY INTEGRATED MICROHEATERS

This thesis work focuses on the investigation of the pyroelectric effect from the –Z surface of Lithium (LiNbO3) crystal using different microheater (µH) designs fabricated on the +Z surface of the crystal. Thermal analyses of the microheater designs were performed both theoretically and experimentally using COMSOL™ Multiphysics and FLIR SC7000 thermocamera respectively. The pyroelectric effect was investigated analysing the current impulses detected using a metallic probe detector connected to an oscilloscope. The temperature variation induced by the microheater causes a spontaneous polarization in the crystal resulting in the formation surface bound charges. The electric field generated between the probe and the crystal surface causes the charge emission that appears as a voltage impulse on the oscilloscope. In an ambient condition, the air layer act as a dielectric thin film layer at few hundreds of microns between the detector probe and crystal surface gap spacing. It was demonstrated and validated that the threshold field strength require to generate the PE was near the dielectric breakdown of air. The pyroelectric emission shows a higher dependency on the rate of thermalization of the microheater and also the electric field generated between the probes to surface gap spacing’s of crystal. The deep characterization of µHs is investigated, in order to demonstrate the reliability and the effectiveness of these microdevices for all those applications where compact and low-power consuming electrical field sources are highly desirable

Impact of thermal material properties and local ion concentration on Ti/HfOx-based analog devices

The realization of adaptive oxides for neuromorphic computing hinges on repeatable and predicable analog changes of electrical resistance, which is fundamentally controlled by the materials in and around the device. This work focuses on filamentary memristors which exhibit a non-volatile change in resistance by modulating the concentration of oxygen vacancies within a small (filamentary) region of an otherwise insulating oxide layer in a metal-insulator-metal (MIM) stack. Under an applied electric field, these devices experience localized temperature rises over 1000 K on picosecond timescales, with drift, diffusion, and thermophoresis causing the migration of oxygen ions and oxygen vacancies. All three of these mechanisms have a strong dependence on temperature. Therefore, the management of the thermal field is crucial to successful implementation of these materials and devices. This dissertation independently establishes the impact of the substrate and electrode thermal conductivity both experimentally and computationally. For biologically realistic pulse widths, low substrate thermal conductivities led to increased resistance changes in RRAM devices. Furthermore, scanning thermal microscopy was used to compare the in-situ temperature rise of the top electrode directly above the filament with the estimated value from the model. This established a method to estimate the filament temperature during biasing with an accuracy ~30 K. Computational results demonstrated the temperature of the capping layer (between the oxide and the top electrode) had the greatest impact on the resistance change. Thus, a low thermal conductivity capping layer led to significantly higher resistance changes. Further work exploring the importance of the capping layer revealed that slightly higher initial oxygen concentrations (~2 - 3%) caused larger resistance changes compared to lower concentrations. In summary, this work establishes the importance of the thermal properties not only in contact with the filament, but also far away (substrate and electrodes) and establishes the importance of understanding the interplay between the filament and the capping layer to further improve the analog resistance change of filamentary RRAMs.Ph.D

Liquid Metal Printing with Scanning Probe Lithography for Printed Electronics

In den letzten Jahren hat das „Internet der Dinge“ (Englisch Internet of Things, abgekürzt IoT), das auch als Internet of Everything (Deutsch frei „Internet von Allem“) bezeichnet wird, mit dem Aufkommen der „Industrie 4.0“ einen Strom innovativer und intelligenter sensorgestützter Elektronik der neuen Generation in den Alltag gebracht. Dies erfordert auch die Herstellung einer riesigen Anzahl von elektronischen Bauteilen, einschließlich Sensoren, Aktoren und anderen Komponenten. Gleichzeitig ist die herkömmliche Elektronikfertigung zu einem hochkomplexen und investitionsintensiven Prozess geworden. In dem Maße, wie die Zahl der elektronischen Bauteile und die Nachfrage nach neuen, fortschrittlicheren elektronischen Bauteilen zunimmt, steigt auch die Notwendigkeit, effizientere und nachhaltigere Wege zur Herstellung dieser Bauteile zu finden. Die gedruckte Elektronik ist ein wachsender Markt, der diese Nachfrage befriedigen und die Zukunft der Herstellung von elektronischen Geräten neu gestalten könnte. Sie erlaubt eine einfache und kostengünstige Produktion und ermöglicht die Herstellung von Geräten auf Papier- oder Kunststoffsubstraten. Für die Herstellung gibt es dabei eine Vielzahl von Methoden. Techniken auf der Grundlage der Rastersondenlithografie waren dabei schon immer Teil der gedruckten Elektronik und haben zu Innovationen in diesem Bereich geführt. Obwohl die Technologie noch jung ist und der derzeitige Stand der gedruckten Elektronik im industriellen Maßstab, wie z. B. die Herstellung kompletter integrierter Schaltkreise, stark limitiert ist, sind die potenziellen Anwendungen enorm. Im Mittelpunkt der Entwicklung gedruckter elektronischer Schaltungen steht der Druck leitfähiger und anderer funktionaler Materialien. Die meisten der derzeit verfügbaren Arbeiten haben sich dabei auf die Verwendung von Tinten auf Nanopartikelbasis konzentriert. Die Herstellungsschritte auf der Grundlage von Tinten auf Nanopartikelbasis sind komplizierte Prozesse, da sie das Ausglühen (Englisch Annealing) und weitere Nachbearbeitungsschritte umfassen, um die gedruckten Muster leitfähig zu machen. Die Verwendung von Gallium-basierten, bei/nahe Raumtemperatur flüssigen Metallen und deren direktes Schreiben für vollständig gedruckte Elektronik ist immer noch ungewöhnlich, da die Kombination aus dem Vorhandensein einer Oxidschicht, hohen Oberflächenspannungen und Viskosität ihre Handhabung erschwert. Zu diesem Zweck zielt diese Arbeit darauf ab, Methoden zum Drucken von Materialien, einschließlich Flüssigmetallen, zu entwickeln, die mit den verfügbaren Druckmethoden nicht oder nur schwer gedruckt werden können und diese Methoden zur Herstellung vollständig gedruckter elektronischer Bauteile zu verwenden. Weiter werden Lösungen für Probleme während des Druckprozesses untersucht, wie z. B. die Haftung der Tinte auf dem Substrat und andere abscheidungsrelevante Aspekte. Es wird auch versucht, wissenschaftliche Fragen zur Stabilität von gedruckten elektronischen Bauelementen auf Flüssigmetallbasis zu beantworten. Im Rahmen der vorliegenden Arbeit wurde eine auf Glaskapillaren basierenden Direktschreibmethode für das Drucken von Flüssigmetallen, hier Galinstan, entwickelt. Die Methode wurde auf zwei unterschiedlichen Wegen implementiert: Einmal in einer „Hochleistungsversion“, basierend auf einem angepassten Nanolithographiegerät, aber ebenfalls in einer hochflexiblen, auf Mikromanipulatoren basierenden Version. Dieser Aufbau erlaubt einen on-the-fly („im Fluge“) kapillarbasierten Druck auf einer breiten Palette von Geometrien, wie am Beispiel von vertikalen, vertieften Oberflächen sowie gestapelten 3D-Gerüsten als schwer zugängliche Oberflächen gezeigt wird. Die Arbeit erkundet den potenziellen Einsatz dieser Methode für die Herstellung von vollständig gedruckten durch Flüssigmetall ermöglichten Bauteilen, einschließlich Widerständen, Mikroheizer, p-n-Dioden und Feldeffekttransistoren. Alle diese elektronischen Bauelemente werden ausführlich charakterisiert. Die hergestellten Mikroheizerstrukturen werden für temperaturgeschaltete Mikroventile eingesetzt, um den Flüssigkeitsstrom in einem Mikrokanal zu kontrollieren. Diese Demonstration und die einfache Herstellung zeigt, dass das Konzept auch auf andere Anwendungen, wie z.B. die bedarfsgerechte Herstellung von Mikroheizern für in-situ Rasterelektronenmikroskop-Experimente, ausgeweitet werden kann. Darüber hinaus zeigt diese Arbeit, wie PMMA-Verkapselung als effektive Barriere gegen Sauerstoff und Feuchtigkeit fungiert und zusätzlich als brauchbarer mechanischer Schutz der auf Flüssigmetall basierenden gedruckten elektronischen Bauteile wirken kann. Insgesamt zeigen der alleinstehende, integrierte Herstellungsablauf und die Funktionalität der Geräte, dass das Potenzial des Flüssigmetall-Drucks in der gedruckten Elektronik viel größer ist als einzig die Verwendung zur Verbindung konventioneller elektronischer Bauteile. Neben der Entwicklung von Druckverfahren und der Herstellung elektronischer Bauteile befasst sich die Arbeit auch mit der Korrosion und der zusätzlichen Legierung von konventionellen Metallelektroden in Kontakt mit Flüssigmetallen, welche die Stabilität der Bauteil beinträchtigen könnten. Zu diesem Zweck wurde eine korrelierte Materialinteraktionsstudie von gedruckten Galinstan- und Goldelektroden durchgeführt. Durch die kombinierte Anwendung von optischer Mikroskopie, vertikaler Rasterinterferometrie, Rasterelektronenmikroskopie, Röntgenphotonenspektroskopie und Rasterkraftmikroskopie konnte der Ausbreitungsprozess von Flüssigmetalllinien auf Goldfilmen eingehend charakterisiert werden. Diese Studie zeigt eine unterschiedliche Ausbreitung der verschiedenen Komponenten des Flüssigmetalls sowie die Bildung von intermetallischen Nanostrukturen auf der umgebenden Goldfilmoberfläche. Auf der Grundlage der erhaltenen zeitabhängigen, korrelierten Charakterisierungsergebnisse wird ein Modell für den Ausbreitungsprozess vorgeschlagen, das auf dem Eindringen des Flüssigmetalls in den Goldfilm basiert. Um eine ergänzende Perspektive auf die interne Nanostruktur zu erhalten, wurde die Röntgen-Nanotomographie eingesetzt, um die Verteilung von Gold, Galinstan und intermetallischen Phasen in einem in das Flüssigmetall getauchten Golddraht zu untersuchen. Schlussendlich werden Langzeitmessungen des Widerstands an Flüssigmetallleitungen, die Goldelektroden verbinden, durchgeführt, was dazu beiträgt, die Auswirkungen von Materialwechselwirkungen auf elektronische Anwendungen zu bewerten

Pressure and thermal effects on superhydrophobic friction reduction in a microchannel flow

textAs the fluidic devices are miniaturized to improve portability, the friction of the microchannel becomes intrinsically high and a high pumping power will be required to drive the fluid. Since the pumping power delivered by portable devices is limited, one method to reduce this is to render the surface to become slippery. This can be achieved by roughening up the microchannel wall and form a bed of air pockets between the roughness elements, which is known as the superhydrophobic Cassie-Baxter state. While the study on superhydrophobic microchannels are focused mainly in maximizing the friction reduction effects and maintaining the stability of the air pockets, less attention has been given to characterizing the microchannel friction under a metastable state, where partial flooding of the micro-textures may be present, and under heated conditions, where the air pockets are trapped between the micro-textures. In order to quantify the frictional characteristics, microchannels with micron-sized trenches on the side walls were fabricated and tested under varying inlet pressures and heating conditions. By measuring the hydrodynamic resistance and comparing with numerical simulations, results suggest that (1) the air-water interface behaves close to a no-slip boundary condition, (2) friction becomes insensitive to the wetting degree once the micro-trenches become highly wetting, (3) the fully wetted micro-trench may be beneficial over the de-wetted ones in order to achieve friction reduction effects and (4) heating the micro-trenches to induce a highly de-wetting state may actually be detrimental to the microchannel flow due the excessive growth of the air layer. As part of the future work to characterize heat transfer in superhydrophobic microchannels, a rectangular microchannel with microheaters embedded close to the side walls was fabricated and the corresponding heat transfer rates were measured through dual fluorescence thermometry. Results suggested that significant heat is lost through the environment despite the high thermal resistance of the microchannel material. An extra insulation is suggested prior to characterizing the convective heat transfer coefficients in the superhydrophobic microchannel flow.Mechanical Engineerin

Developing integrated optical structures, with special respect to applications in medical diagnostics

In my dissertation, I described two label-free optical biosensors based on integrated optical (IO) structures for the sensitive, rapid detection of pathogens - bacterial cells, viral proteins - from fluid samples, which can serve as a basis for rapid clinical tests. These types of devices provide a specific, cost-effective, user-friendly and portable way of detection with sufficient sensitivity by changing the optical signal. Thus, in practice, they could potentially be used as point-of-care (POC) or home rapid diagnostic tests, offering a promising alternative to traditional laboratory assays. Their realization is supported by their integration with microfluidic channels in a lab-on-a-chip (LOC) device, for handling small volumes of fluid. Based on these aspects, biosensors were designed as waveguides, integrated in a microfluidic channel on a glass substrate, performing evanescent-field sensing. The detection method is based on the fact that the light, propagating in the waveguide with total internal reflections, penetrates into the surrounding media at a limited extent, which is called the evanescent field. Material can enter this space and become bound to the surface, which can change the phase of the light, propagating in the structure, or even scatter it into the surrounding medium. These phenomena offer the possibility of specific detection of pathogens, adhering to the surface, pre-coated with a biological recognition element, such as an antibody. As a first application, an electro-optical biosensor was developed with an evanescent field-based detection concept, aiming at label-free, rapid, selective and sensitive detection of bacteria from body fluids. The usability of the measurement principle, based on the processing of light-scattering patterns, caused by evanescent waves, scattered on target cells, was demonstrated by quantitative detection of Escherichia coli bacterial cells from their suspensions. One of the keys to the applicability of biosensors is their sensitivity. To increase it in case of this device, I applied the phenomenon of dielectrophoresis using the polarizability of the target cells. It provides the possibility to selectively collect cells on the surface of electrodes placed close to the waveguide and then detect them based on the evanescent field. To test this, I wanted to sense bacteria in an artificial urine sample containing somatic cells, in this case endothelial cells, mimicking urine in an inflammatory state. By optimizing the parameters of the measurements, a rapid, sensitive bacterial detection of about 10 minutes was achieved. The detection limit of the biosensor was comparable to the characteristic pathogen concentration in body fluids. Furthermore, selective bacterial detection was also achieved from a fluid sample containing somatic cells, mimicking inflammatory urine. In my dissertation, a second application is also presented, in this case a miniature IO Mach-Zehnder interferometer-based biosensor was developed for the specific quantitative detection of viral proteins. Thanks to the interferometric measurement principle, a fast and accurate detection of target proteins can be achieved. With this device, the aim was to investigate the potential neuroinvasion of coronavirus (SARS-CoV-2) infection, from which point of view the pathological effects of viral surface spike proteins on the blood-brain barrier are of great importance in the case of severe symptoms. Furthermore, infection may also cause adverse effects in the intestinal tract. Thus, the specific aim of this application was to evaluate the ability of the S1 subunit of the coronavirus surface spike protein to cross the human in vitro blood-brain barrier and intestinal epithelial biological barrier system models using the biosensor. Experiments were designed to use the sensor for specific, quantitative detection of spike proteins, that may have been passed through permeability assays on biological barrier models prepared by our collaborators. To reach the specific sensing of the target protein, the waveguide surface of the interferometer’s measuring arm was functionalized with specific S1 protein antibody. To achieve optimal, stable measurement conditions, the operating point of the interferometer was adjusted thermo-optically. The results of the experiments with the biosensor were in agreement with the ones of the conventional immunological tests (ELISA) carried out in parallel. It was possible to determine that S1 protein could pass through the two types of barriers in different amounts. The findings of the experiments with the integrated optical Mach-Zehnder interferometer biosensor demonstrate that this detection approach can be used for similar medical diagnostic purposes, and thus can contribute to the investigation of the adverse effects of SARS-CoV-2 on the human body

Design, Simulation and Modeling of a Micromachined High Temperature Microhotplate for Application in Trace Gas Detection

A microhotplate (MHP) is a basic Microelectromechanical System (MEMS) structure that is used in many applications such as a platform for metal oxide gas sensors, microfluidics and infrared emission. Semiconductor gas sensors usually require high power because of their elevated operating temperatures. The uniformity of the temperature distribution over the sensing area is an important factor in gas detection. There are several silicon micromachined MHP that can easily withstand temperatures between 200°C and 500°C for long periods. However there is no systematic study on the effect of the thickness of the various layers of the MHP on its characteristics at high operating temperatures of up to 700oC with lower power dissipation, lower mechanical displacement and good uniformity of the temperature distribution on the MHP. The MHP for the present study consists of a 100 μm × 100 μm membrane supported by four microbridges of length 113 μm and width 20 μm designed and simulated using CoventorWare. Tetrahedron mesh with 80μm element size is applied to the solid model, while the membrane area is meshed with 5μm element size to obtain accurate FEM simulation results. In the characterization of the MHP, the length and width of the various layers (membrane, heat distributor and sensing film) are fixed while their thicknesses are varied from 0.3 μm to 3 μm to investigate the effect of thickness on the MHP characteristics. At the fixed operation temperature of 700°C, it is shown that as membrane thickness increases, power dissipation, current density, time constant and heat transfer to the silicon substrate increases, while mechanical displacement of the membrane remains constant. When the SiC heat distributor thickness increases, a small increase in power dissipation is observed while the displacement decreases. The temperature gradient on the MHP is found to decrease with increasing thickness of the SiC and is a minimum with a value of 0.005°C/μm for a thickness of 2 μm and above. An optimized MHP device at an operating temperature of 700°C was found to have a low power dissipation of about 9.25 mW, maximum mechanical displacement of 1.2 μm, a temperature gradient of 0.005°C/μm and a short time constant of 0.17 ms