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.

CrowdProcess: design numa startup de computação distribuída

Este estágio, realizado na CrowdProcess, consistiu em integrar a equipa da empresa, trabalhando na área do Design de Comunicação, Web e Gráfico, integrado no Departamento de Comunicação da empresa. A CrowdProcess é uma plataforma de computação distribuída que utiliza o poder de processamento dos browsers ligados para correr tarefas de computação distribuída. Uma vez que se trata de um produto online, a maioria do trabalho desenvolvido diz respeito a design e desenvolvimento web e apenas uma pequena parte dedicada a design gráfico. O trabalho foi desenvolvido com as linguagens HTML, CSS e JavaScript. Foram tidos em consideração os princípios de Design, Usabilidade e Arquitectura de Informação, com principal foco na prototipagem dos vários objectos desenvolvidos.

Proceedings of the eighth International Conference on Axiomatic Design (ICAD 2014)

ICAD2014, Campus de Caparica, Portugal

New visualization model for large scale biosignals analysis

Benefits of long-term monitoring have drawn considerable attention in healthcare. Since the acquired data provides an important source of information to clinicians and researchers, the choice for long-term monitoring studies has become frequent. However, long-term monitoring can result in massive datasets, which makes the analysis of the acquired biosignals a challenge. In this case, visualization, which is a key point in signal analysis, presents several limitations and the annotations handling in which some machine learning algorithms depend on, turn out to be a complex task. In order to overcome these problems a novel web-based application for biosignals visualization and annotation in a fast and user friendly way was developed. This was possible through the study and implementation of a visualization model. The main process of this model, the visualization process, comprised the constitution of the domain problem, the abstraction design, the development of a multilevel visualization and the study and choice of the visualization techniques that better communicate the information carried by the data. In a second process, the visual encoding variables were the study target. Finally, the improved interaction exploration techniques were implemented where the annotation handling stands out. Three case studies are presented and discussed and a usability study supports the reliability of the implemented work.

Technology transition towards electric mobility - technology assessment as a tool for policy design

Paper presented at the Colloquium Gerpisa 2013, Paris (http://gerpisa.org/node/2085), Session n°: 19 New kinds of mobility: old and new business models

Design e fabrico de novos eléctrodos impressos em papel para desenvolvimento de biossensores enzimáticos com aplicações biomédicas

Num mundo em crescente evolução é necessário tentar melhorar as condições de saúde global. Um factor importante para a prevenção e tratamento de doenças é o seu correcto diagnóstico. Uma vez que nem todos os países têm a mesma capacidade económica, existe a necessidade de se criar testes rápidos e baratos que possam ser acessíveis no mundo inteiro. Os point-of-care tests, como é o caso dos biossensores de glucose vastamente utilizados na monitorização da diabetes, apresentam uma solução para este problema. Os biossensores impressos em papel, em particular, são uma ferramenta que pode vir a ser muito útil na construção destes testes rápidos tornando-os mais “amigos do ambiente” e reduzindo os seus custos. O objectivo deste trabalho foi desenvolver biossensores enzimáticos, de segunda geração, impressos em papel e baseados na enzima glucose oxidase, para a detecção da glucose. Inicialmente foi feito um estudo de possíveis mediadores a utilizar, tendo-se escolhido o ferroceno por apresentar um limite de detecção adequado, ter apresentado um valor de potencial de redução relativamente baixo, 0.232 V vs pseudo ref. Ag/AgCl, ser um composto fácil de obter e com custos reduzidos. Os dispositivos baseiam-se em canais microfluídicos, eléctrodos e ligações eléctricas fabricadas em substrato de papel, utilizando as técnicas de impressão a cera, screen printing e inkjet printing. O circuito constituinte destes dispositivos foi feito recorrendo a tintas condutoras, sendo que, à tinta utilizada para o eléctrodo de trabalho foi incorporado o ferroceno. Sobre o eléctrodo de trabalho foi impressa glucose oxidase, utilizando a técnica de inkjet printing. Os eléctrodos fabricados apresentaram resposta à glucose, muito embora com baixa reprodutibilidade, podendo esta ser causada pela falta de controlo na preparação dos mesmos (manufactura manual e variabilidade da viscosidade da pasta usada no eléctrodo de trabalho). A técnica de inkjet printing em enzimas é ainda muito recente, existindo ainda alguns aspectos, como o seu efeito na actividade da enzima, que não foram avaliados neste projecto, mas que no futuro deverão ser estudados. Podemos concluir que, os eléctrodos deram uma resposta electroquímica consistente à adição de glucose, 8 mM- 30 mM, sendo que os mesmos foram reconhecidos no glucómetro comercial TRUETrackTM blood glucometer; no entanto, os valores de corrente dos dispositivos estavam abaixo do limite de detecção do instrumento.

Learning facial-expression models with crowdsourcing

The computational power is increasing day by day. Despite that, there are some tasks that are still difficult or even impossible for a computer to perform. For example, while identifying a facial expression is easy for a human, for a computer it is an area in development. To tackle this and similar issues, crowdsourcing has grown as a way to use human computation in a large scale. Crowdsourcing is a novel approach to collect labels in a fast and cheap manner, by sourcing the labels from the crowds. However, these labels lack reliability since annotators are not guaranteed to have any expertise in the field. This fact has led to a new research area where we must create or adapt annotation models to handle these weaklylabeled data. Current techniques explore the annotators’ expertise and the task difficulty as variables that influences labels’ correction. Other specific aspects are also considered by noisy-labels analysis techniques. The main contribution of this thesis is the process to collect reliable crowdsourcing labels for a facial expressions dataset. This process consists in two steps: first, we design our crowdsourcing tasks to collect annotators labels; next, we infer the true label from the collected labels by applying state-of-art crowdsourcing algorithms. At the same time, a facial expression dataset is created, containing 40.000 images and respective labels. At the end, we publish the resulting dataset.

Design of a CMOS amplifier for breast cancer detection

A transimpedance amplifier (TIA) is used, in radiation detectors like the positron emission tomography(PET), to transform the current pulse produced by a photo-sensitive device into an output voltage pulse with a desired amplitude and shape. The TIA must have the lowest noise possible to maximize the output. To achieve a low noise, a circuit topology is proposed where an auxiliary path is added to the feedback TIA input, In this auxiliary path a differential transconductance block is used to transform the node voltage in to a current, this current is then converted to a voltage pulse by a second feedback TIA complementary to the first one, with the same amplitude but 180º out of phase with the first feedback TIA. With this circuit the input signal of the TIA appears differential at the output, this is used to try an reduced the circuit noise. The circuit is tested with two different devices, the Avalanche photodiodes (APD) and the Silicon photomultiplier (SIPMs). From the simulations we find that when using s SIPM with Rx=20kΩ and Cx=50fF the signal to noise ratio is increased from 59 when using only one feedback TIA to 68.3 when we use an auxiliary path in conjunction with the feedback TIA. This values where achieved with a total power consumption of 4.82mv. While the signal to noise ratio in the case of the SIPM is increased with some penalty in power consumption.

Design of a low-voltage CMOS RF receiver for energy harvesting sensor node

In this thesis a CMOS low-power and low-voltage RF receiver front-end is presented. The main objective is to design this RF receiver so that it can be powered by a piezoelectric energy harvesting power source, included in a Wireless Sensor Node application. For this type of applications the major requirements are: the low-power and low-voltage operation, the reduced area and cost and the simplicity of the architecture. The system key blocks are the LNA and the mixer, which are studied and optimized with greater detail, achieving a good linearity, a wideband operation and a reduced introduction of noise. A wideband balun LNA with noise and distortion cancelling is designed to work at a 0.6 V supply voltage, in conjunction with a double-balanced passive mixer and subsequent TIA block. The passive mixer operates in current mode, allowing a minimal introduction of voltage noise and a good linearity. The receiver analog front-end has a total voltage conversion gain of 31.5 dB, a 0.1 - 4.3 GHz bandwidth, an IIP3 value of -1.35 dBm, and a noise figure lower than 9 dB. The total power consumption is 1.9 mW and the die area is 305x134.5 m2, using a standard 130 nm CMOS technology.

Design, implementation, and performance of a distributed and scalable sensor system for critical distance measurements in the CMS detector at LHC

The “CMS Safety Closing Sensors System” (SCSS, or CSS for brevity) is a remote monitoring system design to control safety clearance and tight mechanical movements of parts of the CMS detector, especially during CMS assembly phases. We present the different systems that makes SCSS: its sensor technologies, the readout system, the data acquisition and control software. We also report on calibration and installation details, which determine the resolution and limits of the system. We present as well our experience from the operation of the system and the analysis of the data collected since 2008. Special emphasis is given to study positioning reproducibility during detector assembly and understanding how the magnetic fields influence the detector structure.

Bioprocess design of canine adenovirus vectors for gene therapy applications

The potential of human adenovirus vectors as vehicles for gene transfer with clinical applications in vaccination, cancer treatment and in many monogenic and acquired diseases has been demonstrated in several studies and clinical trials. However, the clinical use of these vectors can be limited by pre-existing humoral and cellular anti-capsid immunity. One way to circumvent this bottleneck while keeping the advantages of using adenovirus vectors is using non-human viruses such as Canine Adenovirus type 2 (CAV-2). Moreover, CAV-2 vectors present attractive features to develop potential treatment of neurodegenerative and ocular disorders. While the interest in CAV-2 vectors increases, scalable and robust production processes are required to meet the need for preclinical and possibly clinical uses.(...)

Web Design como ferramenta de Comunicação Digital

WEB DESIGN COMO FERRAMENTA DE COMUNICAÇÃO DIGITAL: DESIGN E DESENVOLVIMENTO DE SITES, UTILIZANDO O GESTOR DE CONTEÚDOS WORDPRESS; DESIGN DE CONTEÚDOS VISUAIS PARA O FACEBOOK DE UMA MARCA

Business concept design of an innovative product: Partnership between Nmusic and Rovio Entertainment Ltd.

Field Lab in Entrepreneurial Innovative Ventures

Machine ethics via logic programming

Machine ethics is an interdisciplinary field of inquiry that emerges from the need of imbuing autonomous agents with the capacity of moral decision-making. While some approaches provide implementations in Logic Programming (LP) systems, they have not exploited LP-based reasoning features that appear essential for moral reasoning. This PhD thesis aims at investigating further the appropriateness of LP, notably a combination of LP-based reasoning features, including techniques available in LP systems, to machine ethics. Moral facets, as studied in moral philosophy and psychology, that are amenable to computational modeling are identified, and mapped to appropriate LP concepts for representing and reasoning about them. The main contributions of the thesis are twofold. First, novel approaches are proposed for employing tabling in contextual abduction and updating – individually and combined – plus a LP approach of counterfactual reasoning; the latter being implemented on top of the aforementioned combined abduction and updating technique with tabling. They are all important to model various issues of the aforementioned moral facets. Second, a variety of LP-based reasoning features are applied to model the identified moral facets, through moral examples taken off-the-shelf from the morality literature. These applications include: (1) Modeling moral permissibility according to the Doctrines of Double Effect (DDE) and Triple Effect (DTE), demonstrating deontological and utilitarian judgments via integrity constraints (in abduction) and preferences over abductive scenarios; (2) Modeling moral reasoning under uncertainty of actions, via abduction and probabilistic LP; (3) Modeling moral updating (that allows other – possibly overriding – moral rules to be adopted by an agent, on top of those it currently follows) via the integration of tabling in contextual abduction and updating; and (4) Modeling moral permissibility and its justification via counterfactuals, where counterfactuals are used for formulating DDE.

Strategic design of There App’s business model: From product to multi-sided platform

The following work project illustrates the strategic issues There App, a mobile application, faces regarding the opportunity to expand from its current state as a product to a multisided platform. Initially, a market analysis is performed to identify the ideal customer groups to be integrated in the platform. Strategic design issues are then discussed on how to best match its value proposition with the identified market opportunity. Suggestions on how the company should organize its resources and operational processes to best deliver on its value proposition complete the work.