Despite the last 60 years have seen major advances in many scientific and technological inputs of drug Research and Development, the number of new molecules hitting the market per billion US dollars of R&D spending has been declined steadily during the same period. The current scenario highlights the need for new research tools to enable reduce costly animal and clinical trials while providing a better prediction about drug efficacy and security in humans A recent emerging approach to improve the current models is emerging from the field of microfluidics, which studies systems that process or manipulate tiny amounts of fluids using channels with dimensions of tens to hundreds of micrometers. Combining microfluidics with cell culture, scientists gave rise to a new field named “Organ-on-chip” (OOC). Microfluidic OOCs are advanced platforms designed to mimic physiological structures and continuous flow conditions, thus allowing the culture of cells in a friendlier microenvironment. This thesis, titled “Cell culture interfaces for different organ-on-chip applications: from photolithography to rapid-prototyping techniques with sensor embedding”, aims to design, simulate and test new OOC devices to reproduce cell culture interface under flow conditions. The work has a focus on the exploration of novel fabrication techniques which enable rapid prototyping of OOC devices, reducing costs, time and human labor associated to the fabrication process. The final objective is to demonstrate the viability of the devices as research tools for biological problems, applying them to the tubular kidney and the blood brain barrier (BBB). To achieve the objective, at least three device version have been developed: 1) OOCv1, fabricated by multilayer PDMS soft lithography; 2) OOCv2, fabricated in thermoplastic by layered object manufacturing using both a vinyl cutter and a laser cutter, integrating standard fluidic connectors alone (OOCv2.1) or together with embedded electrodes (OOCv2.2); 3) OOCv3 using a mixed technique of laser cut and 3D printing by stereolithography. All devices are fabricated using biocompatible materials with high optical quality and an embedded commercial membrane. The biological experiments with renal tubular epithelial cells, realized on OOCv1 and OOCv2.1 devices, demonstrated the viability of the device for culturing cells under flow conditions. The study realized on fatty acid oxidation and accumulation in cells exposed to physiological and diabetogenic oscillating levels of glucose suggest a possible positive role of shear stress in activation of fatty acid metabolism. The studies were performed using a compact experimental unit with embedded flow control which reduce significatively the complexity and cost of the fluidic experimental setup. The biological experiments on the BBB confirmed viability of OOCv2.1 and OOCv2.2 for compartmentalized co-culturing of endothelial cells and pericytes. The formation and recovery of the barrier after disruptive treatment has been assessed using different techniques, including immunostaining, fluorescence and live phase contrast imaging, and electrical impedance spectroscopy. The repeatability of measurements using electrodes was verified. A model to classify measurements from different timepoints has been developed, resulting in accuracy of 100% in learning and 90% in testing case. Results are confirmed by imaging data, which also suggest a critical role of pericytes in the development, maintenance, and regulation of BBB, in accordance with the literature.
Usó, Vanessa Ghiraldeli, Sandnes, Frode Eika, and Medola, Fausto Orsi
Usó, V.G., Sandnes, F.E. & Medola, F.O. (2020). Using virtual reality and rapid prototyping to co-create together with hospitalized children. In: M. Di Nicolantonio, E. Rossi & T. Alexander (Eds.). Advances in additive manufacturing, modeling systems and 3D prototyping: Proceedings of the AHFE 2019 International Conference on Additive Manufacturing, Modeling Systems and 3D Prototyping, 2020 (pp. 279-288) Cham: Springer
The present work addresses two different applications enabled by a specific and useful property of calcium phosphate cements (CPCs): injectability. On the one hand minimally invasive procedures involving the use of CPCs are based on the injectability of such biomaterials, and on the other hand extrusion-based additive manufacturing processes such as robocasting rely on this property to correctly manufacture personalized 3D-printed scaffolds for the treatment of large bone defects. The present thesis is divided in three different sections. The first one consists in a study of the differences of injectability of aqueous pastes of the two allotropic forms of tricalcium phosphate, namely a- and ß-TCP. The reactivity of the powder was shown to play a significant role in the injectability of TCP pastes. Significant differences were observed between the injection behaviour of non-hardening ß-TCP pastes and that of selfhardening a-TCP pastes. The differences were more marked at low liquid-to-powder ratios, using fine powders and injecting through thin needles. Although, as a general trend, faster-setting pastes were less injectable, some exceptions to this rule were found. For example, whereas in the absence of setting accelerants fine TCP powders were more injectable than the coarse ones, in spite of their shorter setting times, this trend was inverted when setting accelerants were added, and coarse powders were more injectable than the fine ones. In the second section thermoresponsive pastes are developed through the combination of CPCs with an inversethermoresponsive hydrogel. Although calcium phosphate cements (CPCs) are used for bone regeneration in a wide range of clinical applications, various physicochemical phenomena are known to hinder their potential use in minimally invasive surgery or in highly vascularized surgical sites, mainly because of their lack of injectability or their low washout resistance. The proposed strategy allowed to finely tune the cohesive and rheological properties of CPCs to achieve clinical acceptable injectability. It avoided phase separation during implantation and improved cohesion, avoiding washout of the paste. Using the knowledge acquired about the injectability behaviour of TCP pastes, the additive manufacturing of 3D printed scaffolds is studied in the last section. More precisely, this study dealt with the robocasting of alpha-tricalcium phosphate/gelatine reactive slurries as a bioinspired self-setting ink for the production of biomimetic hydroxyapatite/gelatine scaffolds. A controlled and totally interconnected pore network of approximately 300 µm was obtained after ink printing and setting, with the struts consisting of a micro/nanoporous matrix of needle-shaped calcium deficient hydroxyapatite crystals, with a high specific surface area. Gelatine was effectively retained by chemical crosslinking. The setting reaction of the ink resulted in a significant increase of both the elastic modulus and the compressive strength of the scaffolds, which were within the range of the human trabecular bone. In addition to delaying the onset of the setting reaction, thus providing enough time for printing, gelatine provided the viscoelastic properties to the strands to support their own weight, and additionally enhanced mesenchymal stem cell adhesion and proliferation on the surface of the scaffold. Altogether this new processing approach opens good perspectives for the design of hydroxyapatite scaffolds for bone tissue engineering with enhanced reactivity and resorption rate.
El objetivo de esta tesis es el de la mejora del rendimiento de dispositivos electroquímcos miniaturizados, con énfasis en pilas de combustible microbianas y sensores electroquímicos. Para conseguir este objetivo, está tesis está centrada en el desarrollo de nuevos materiales para electrodos, nuevas geometrías para microelectrodos y mejor fabricación y procesos de encapsulado. Un inconveniente muy importante en la miniaturización de dispositivos electroquímicos está en la reducción de al superficie activa de los electrodos resultado en señales más pequeñas. Sin embargo, la introducción de técnicas de micromecanizado de silicio como pueden ser fotolitografía grabados seco y húmedo, deposición de metales o dieléctricos por métodos físicos o químicos o procesos térmicos rápidos se han convertido en una vía real para solventar todos los problemas relacionados la manufacturación de dispositivos electroquímicos miniaturizados. Además el uso de herramientas computacionales basadas en métodos de elementos finitos ha ayudado extraordinariamente al diseño de estos dispositivos porque la quinética del electrodo y el transporte de masa pueden ser simulados y estudiados antes de su fabricación. El primer capítulo es una introducción a los fundamentos de la electroquímica, al diseño, a la fabricación y a las aplicaciones desarrolladas en esta tesis. La primera sección se centra en explicar los aspectos fundamentales de la electroquímica. La segunda sección introduce las pilas de combustible, porque estos son los dispositivos electroquímicos desarrollados en el capítulo 4. Finalmente la última sección cubre los materiales y métodos utilizados, incluyendo la microfabricación de los electrodos y las técnicas de prototipaje utilizadas para fabricar las pilas de combustible microbianas. El segundo capítulo comienza con la teoría del transporte de masa en micropilares totalmente conductores. A continuación, el modelo computacional de un único dominio de un micropilar es desarrollado utilizando COMSOL. La fabricación de electrodos con arrays de micropilares totalmente conductores fue conseguida por electrodeposición de oro y también por la combinación de grabado seco y metalización por deposición de oro mediante sputtering. El capítulo cierra con la caracterización electroquímica de los dos arrays, lo que permitió comparar su respuesta y averiguar que ruta era la mejor. El capítulo tres se dirige a la síntesis y fabricación de discos de electrodos de carbón para detectar mercurio en muestras acuosas. Estos electrodos de carbón están basados en la pirólisis de fotoresina. Esta técnica combina fotolitografía y procesos térmicos rápidos. Además las ventanas activas de esos electrodos fueron definidas por deposición química de dieléctricos, también los electrodos fueron físicamente y electroquímicamente caracterizados. Una vez estos electrodos fueron completamente estudiados se utilizaron para detectar mercurio en soluciones. El último capítulo se centra en encontrar una aplicación a los electrodos de arrays de micropilares totalmente conductores. La aplicación escogida fue una pila de combustible microbiana miniaturizada fabricada mediante técnicas de prototipaje rápido, donde en cada caso una geometría diferente con el objeto de averiguar si los arrays de micropilares ayudan a mejorar el rendimiento eléctrico de las pilas de combustible microbianas.
In the the last decades several performance walls were hit. The memory wall and the power wall are limiting the performance scaling of digital microprocessors. Homogeneous multicores rely on thread-level parallelism, which is challenging to exploit. New heterogeneous architectures promise higher performance per watt rates, but software simulators have limited capacity to research them. In this thesis we investigate the advantages of Field-Programmable Gate Array devices (FPGA) for multicore research. We developed three prototypes, implementing up to 24 cores in a single FPGA, showing their superior performance and precision compared to software simulators. Moreover, our prototypes perform full-system emulation and are totally modifiable. We use our prototypes to implement novel architectural extensions such as Transactional Memory (TM). This use case allowed us to research different needs that computer architects may have, and how to implement them on FPGAs. We developed several techniques to offer profiling, debugging and verification techniques in each stage of the design process. These solutions may bridge the gap between FPGA-based hardware design and computer architects. In particular, we place a special stress on non-obtrusive techniques, so that the precision of the emulation is not affected. Based on the current trends and the sustained growth in the high-level synthesis community, we expect FPGAs to become an integral part of computer architecture design in the next years.
Caballero Codina, Víctor, Vernet Bellet, David, Zaballos Diego, Agustín, Corral Torruella, Guiomar, and Universitat Ramon Llull. La Salle
RECERCAT (Dipòsit de la Recerca de Catalunya), 2018
Xarxes de sensors and Internet de les coses
Sensor networks and the Internet of Things have driven the evolution of traditional electric power distribution networks towards a new paradigm referred to as Smart Grid. However, the different elements that compose the Information and Communication Technologies (ICTs) layer of a Smart Grid are usually conceived as isolated systems that typically result in rigid hardware architectures which are hard to interoperate, manage, and to adapt to new situations. If the Smart Grid paradigm has to be presented as a solution to the demand for distributed and intelligent energy management system, it is necessary to deploy innovative IT infrastructures to support these smart functions. One of the main issues of Smart Grids is the heterogeneity of communication protocols used by the smart sensor devices that integrate them. The use of the concept of the Web of Things is proposed in this work to tackle this problem. More specifically, the implementation of a Smart Grid’sWeb of Things, coined as theWeb of Energy is introduced. The purpose of this paper is to propose the usage of Web of Energy by means of the Actor Model paradigm to address the latent deployment and management limitations of Smart Grids. Smart Grid designers can use the Actor Model as a design model for an infrastructure that supports the intelligent functions demanded and is capable of grouping and converting the heterogeneity of traditional infrastructures into the homogeneity feature of theWeb of Things. Conducted experimentations endorse the feasibility of this solution and encourage practitioners to point their efforts in this direction.