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.
This article presents a novel methodology to design swash plate type axial piston machines based on computationally based approach. The methodology focuses on the design of the main lubricating interfaces present in a swash plate type unit: the cylinder block/valve plate, the piston/cylinder, and the slipper/swash plate interface. These interfaces determine the behavior of the machine in term of energy efficiency and durability. The proposed method couples for the first time the numerical models developed at the authors’ research center for each separated tribological interface in a single optimization framework. The paper details the optimization procedure, the geometry, and material considered for each part. A physical prototype was also built and tested from the optimal results found from the numerical model. Tests were performed at the authors’ lab, confirming the validity of the proposed method.
Ferrari, A., Novara, C., Paolucci, E., Vento, O., Violante, M., and Zhang, T.
Applied Energy, 2018, 232, C, 358.
Fuel injection system, Diesel engine, Injected mass control, and Rapid prototyping hardware
A closed-loop strategy that is capable of controlling the fuel injected mass in the combustion chamber of a Common Rail diesel engine has been set up. The pressure time histories measured along the rail-to-injector pipe have been used to evaluate the instantaneous mass flow-rate entering the injector. This flow-rate has then been integrated between two time instants, and the thus calculated fuel mass has resulted to correlate well with the injected mass.
András Poppe, Gábor Farkas, Lajos Gaál, Gusztáv Hantos, János Hegedüs, and Márta Rencz
Energies, 2019, 12, 10, 1.
light emitting diodes, power LEDs, multi-domain modelling, and LED luminaire design
This paper presents our approaches to chip level multi-domain LED (light emitting diode) modelling, targeting luminaire design in the Industry 4.0 era, to support virtual prototyping of LED luminaires through luminaire level multi-domain simulations. The primary goal of such virtual prototypes is to predict the light output characteristics of LED luminaires under different operating conditions. The key component in such digital twins of a luminaire is an appropriate multi-domain model for packaged LED devices that captures the electrical, thermal, and light output characteristics and their mutual dependence simultaneously and consistently. We developed two such models with this goal in mind that are presented in detail in this paper. The first model is a semi analytical, quasi black-box model that can be implemented on the basis of the built-in diode models of spice-like circuit simulators and a few added controlled sources. Our second presented model is derived from the physics of the operation of today’s power LEDs realized with multiple quantum well heterojunction structures. Both models have been implemented in the form of visual basic macros as well as circuit models suitable for usual spice circuit simulators. The primary test bench for the two circuit models was an LTspice simulation environment. Then, to support the design of different demonstrator luminaires of the Delphi4LED project, a spreadsheet application was developed, which ensured seamless integration of the two models with additional models representing the LED chips’ thermal environment in a luminaire. The usability of our proposed models is demonstrated by real design case studies during which simulated light output characteristics (such as hot lumens) were confirmed by luminaire level physical tests.
Abstract This paper describes a Grid-like Material Transportation Network (GMTN) in which several heterogeneous means of transportation (Automated Guided Vehicles (AGVs), hoists, lifts, etc.) interact with each other via common shared workstations to provide a variety of demand-responsive material handling operations. Different material handling transport modes provide movement of workpieces between workstations along their manufacturing routes in the GMTN and they can be seen as processes realized with synergic utilization of various local periodically acting unimodal processes. The main contribution of this research is the solution of a constraint satisfaction problem addressing AGVs fleet match-up scheduling subject to GMTN and fuzzy operation time constraints. In the presented case both production rate (production takt) and operations execution time are described by imprecise (fuzzy) data. In other words, the research’s objective concerns assessing grid-like networks of periodically acting local transportation modes from the perspective of possible mass-customized oriented requirements imposed on scheduling of multimodal flows of jobs assigned to certain technological routes passing through common shared workstations.
Amruta V. Kulkarni, Weiqiang Chen, and Ali M. Bazzi
Energies, 2016, 9, 7, 1.
rapid prototyping, design methodology, DC-DC converters, user centered design, user interface, and design optimization
In this paper, power loss and cost models of power electronic converters based on converter ratings and datasheet information are presented. These models aid in creating rapid prototypes which facilitate the component selection process. Through rapid prototyping, users can estimate power loss and cost which are essential in design decisions. The proposed approach treats main power electronic components of a converter as building blocks that can be arranged to obtain multiple topologies to facilitate rapid prototyping. In order to get system-level power loss and cost models, two processes are implemented. The first process automatically provides minimum power loss or cost estimates and identifies components for specific applications and ratings; the second process estimates power losses and costs of each component of interest as well as the whole system. Two examples are used to illustrate the proposed approaches—boost and buck converters in continuous conduction mode. Achieved cost and loss estimates are over 93% accurate when compared to measured losses and real cost data. This research presents derivations of the proposed models, experimental validation of the models and demonstration of a user friendly interface that integrates all the models. Tools presented in this paper are expected to be very useful for practicing engineers, designers, and researchers, and are flexible and adaptable with changing or new technologies and varying component prices.
Technological Forecasting and Social Change, 2016, 102, C, 214.
3D printing, Business models, Innovation, Rapid prototyping, Rapid tooling, Direct Digital manufacturing, Home fabrication, Value creation, and Value capture
There is a growing consensus that 3D printing technologies will be one of the next major technological revolutions. While a lot of work has already been carried out as to what these technologies will bring in terms of product and process innovation, little has been done on their impact on business models and business model innovation. Yet, history has shown that technological revolution without adequate business model evolution is a pitfall for many businesses. In the case of 3D printing, the matter is further complicated by the fact that adoption of these technologies has occurred in four successive phases (rapid prototyping, rapid tooling, digital manufacturing, home fabrication) that correspond to a different level of involvement of 3D printing in the production process. This article investigates the effect of each phase on the key business model components. While the impact of rapid prototyping and rapid tooling is found to be limited in extent, direct manufacturing and, even more so, home fabrication have the potential to be highly disruptive. While much more value can be created, capturing value can become extremely challenging. Hence, finding a suitable business model is critical. To this respect, this article shows that 3D printing technologies have the potential to change the way business model innovation is carried out, by enabling adaptive business models and by bringing the ‘rapid prototyping’ paradigm to business model innovation itself.