Compact simulated countercurrent chromatography for downstream processing of (bio)pharmaceuticals

Dissertação para obtenção do Grau de Doutor em Engenharia Química e Bioquímica

Fractionation of hydro-ethanolic extracts from grape pomace through membrane processing: the effect of membrane and extracting media on process performance

The EM3E Master is an Education Programme supported by the European Commission, the European Membrane Society (EMS), the European Membrane House (EMH), and a large international network of industrial companies, research centers and universities

Optimization of breast tomosynthesis image reconstruction using parallel computing

Breast cancer is the most common cancer among women, being a major public health problem. Worldwide, X-ray mammography is the current gold-standard for medical imaging of breast cancer. However, it has associated some well-known limitations. The false-negative rates, up to 66% in symptomatic women, and the false-positive rates, up to 60%, are a continued source of concern and debate. These drawbacks prompt the development of other imaging techniques for breast cancer detection, in which Digital Breast Tomosynthesis (DBT) is included. DBT is a 3D radiographic technique that reduces the obscuring effect of tissue overlap and appears to address both issues of false-negative and false-positive rates. The 3D images in DBT are only achieved through image reconstruction methods. These methods play an important role in a clinical setting since there is a need to implement a reconstruction process that is both accurate and fast. This dissertation deals with the optimization of iterative algorithms, with parallel computing through an implementation on Graphics Processing Units (GPUs) to make the 3D reconstruction faster using Compute Unified Device Architecture (CUDA). Iterative algorithms have shown to produce the highest quality DBT images, but since they are computationally intensive, their clinical use is currently rejected. These algorithms have the potential to reduce patient dose in DBT scans. A method of integrating CUDA in Interactive Data Language (IDL) is proposed in order to accelerate the DBT image reconstructions. This method has never been attempted before for DBT. In this work the system matrix calculation, the most computationally expensive part of iterative algorithms, is accelerated. A speedup of 1.6 is achieved proving the fact that GPUs can accelerate the IDL implementation.

Microwave imaging of the axilla to aid breast cancer diagnosis

Breast cancer is the most common type of cancer among women all over the world. An important issue that is not commonly addressed in breast cancer imaging literature is the importance of imaging the underarm region—where up to 80% of breast cancer cells can metastasise to. The first axillary lymph nodes to receive drainage from the primary tumour in the breast are called Sentinel Node. If cancer cells are found in the Sentinel Node, there is an increased risk of metastatic breast cancer which makes this evaluation crucial to decide what follow-up exams and therapy to follow. However, non-invasive detection of cancer cells in the lymph nodes is often inconclusive, leading to the surgical removal of too many nodes which causes adverse side-effects for patients. Microwave Imaging is one of the most promising non-invasive imaging modalities for breast cancer early screening and monitoring. This novel study tests the feasibility of imaging the axilla region by means of the simulation of an Ultra-Wideband Microwave Imaging system. Simulations of such system are completed in several 2D underarm models that mimic the axilla. Initial imaging results are obtained by means of processing the simulated backscattered signals by eliminating artefacts caused by the skin and beamforming the processed signals in order to time-align all the signals recorded at each antenna. In this dissertation several image formation algorithms are implemented and compared by visual inspection of the resulting images and through a range of performance metrics, such as Signal-to-Clutter Ratio and FullWidth Half Maximum calculations. The results in this study showed that Microwave Imaging is a promising technique that might allow to identify the presence and location of metastasised cancer cells in axillary lymph nodes, enabling the non-invasive evaluation of breast cancer staging.

Ionic liquids as catalysts of lignocellulosic biomass processing

The present work is devoted to study the pre-treatment of lignocellulosic biomass, especially wheat straw, by the application of the acidic ionic liquid (IL) such as 1-butyl-3-methylimidazolium hydrogen sulphate. The ability of this IL to hydrolysis and conversion of biomass was scrutinised. The pre-treatment with hydrogen sulphate-based IL allowed to obtain a liquor rich in hemicellulosic sugars, furans and organic acids, and a solid fraction mainly constituted by cellulose and lignin. Quantitative and qualitative analyses of the produced liquors were made by capillary electrophoresis and high-performance liquid chromatography. Pre-treatment conditions were set to produce xylose or furfural. Specific range of temperatures from 70 to 175 °C and residence times from 20.0 to 163.3 min were studied by fixing parameters such as biomass/IL ratio (10 % (w/w)) and water content (1.25 % (w/w)) in the pre-treatment process. Statistical modelling was applied to maximise the xylose and furfural concentrations. For the purpose of reaction condition comparison the severity factor for studied ionic liquid was proposed and applied in this work. Optimum conditions for xylose production were identified to be at 125 °C and 82.1 min, at which 16.7 % (w/w) xylose yield was attained. Furfural was preferably formed at higher pre-treatment temperatures and longer reaction time (161 °C and 104.5 min) reaching 30.7 % (w/w) maximum yield. The influence of water content on the optimum xylose formation was also studied. Pre-treatments with 5 and 10 % (w/w) water content were performed and an increase of 100 % and 140 % of xylose yield was observed, respectively, while the conversion into furfural maintained unchanged.

A built-in self-test technique for high speed analog-to-digital converters

Fundação para a Ciência e a Tecnologia (FCT) - PhD grant (SFRH/BD/62568/2009)

UAV - based imagery processing using structure from motion and remote sensing technology

With the recent advances in technology and miniaturization of devices such as GPS or IMU, Unmanned Aerial Vehicles became a feasible platform for a Remote Sensing applications. The use of UAVs compared to the conventional aerial platforms provides a set of advantages such as higher spatial resolution of the derived products. UAV - based imagery obtained by a user grade cameras introduces a set of problems which have to be solved, e. g. rotational or angular differences or unknown or insufficiently precise IO and EO camera parameters. In this work, UAV - based imagery of RGB and CIR type was processed using two different workflows based on PhotoScan and VisualSfM software solutions resulting in the DSM and orthophoto products. Feature detection and matching parameters influence on the result quality as well as a processing time was examined and the optimal parameter setup was presented. Products of the both workflows were compared in terms of a quality and a spatial accuracy. Both workflows were compared by presenting the processing times and quality of the results. Finally, the obtained products were used in order to demonstrate vegetation classification. Contribution of the IHS transformations was examined with respect to the classification accuracy.

Image processing for displacement measurements

Since the invention of photography humans have been using images to capture, store and analyse the act that they are interested in. With the developments in this field, assisted by better computers, it is possible to use image processing technology as an accurate method of analysis and measurement. Image processing's principal qualities are flexibility, adaptability and the ability to easily and quickly process a large amount of information. Successful examples of applications can be seen in several areas of human life, such as biomedical, industry, surveillance, military and mapping. This is so true that there are several Nobel prizes related to imaging. The accurate measurement of deformations, displacements, strain fields and surface defects are challenging in many material tests in Civil Engineering because traditionally these measurements require complex and expensive equipment, plus time consuming calibration. Image processing can be an inexpensive and effective tool for load displacement measurements. Using an adequate image acquisition system and taking advantage of the computation power of modern computers it is possible to accurately measure very small displacements with high precision. On the market there are already several commercial software packages. However they are commercialized at high cost. In this work block-matching algorithms will be used in order to compare the results from image processing with the data obtained with physical transducers during laboratory load tests. In order to test the proposed solutions several load tests were carried out in partnership with researchers from the Civil Engineering Department at Universidade Nova de Lisboa (UNL).

Mobile image processing to support educational geometry games

The mobile IT era is here, it is still growing and expanding at a steady rate and, most of all, it is entertaining. Mobile devices are used for entertainment, whether social through the so-called social networks, or private through web browsing, video watching or gaming. Youngsters make heavy use of these devices, and even small children show impressive adaptability and skill. However not much attention is directed towards education, especially in the case of young children. Too much time is usually spent in games which only purpose is to keep children entertained, time that could be put to better use such as developing elementary geometric notions. Taking advantage of this pocket computer scenario, it is proposed an application geared towards small children in the 6 – 9 age group that allows them to consolidate knowledge regarding geometric shapes, forming a stepping stone that leads to some fundamental mathematical knowledge to be exercised later on. To achieve this goal, the application will detect simple geometric shapes like squares, circles and triangles using the device’s camera. The novelty of this application will be a core real-time detection system designed and developed from the ground up for mobile devices, taking into account their characteristic limitations such as reduced processing power, memory and battery. User feedback was be gathered, aggregated and studied to assess the educational factor of the application.

Improving downstream processing for viral vectors and viral vaccines

Viral vectors are playing an increasingly important role in the vaccine and gene therapy elds. The broad spectrum of potential applications, together with expanding medical markets, drives the e orts to improve the production processes for viral vaccines and viral vectors. Developing countries, in particular, are becoming the main vaccine market. It is thus critical to decrease the cost per dose, which is only achievable by improving the production process. In particular advances in the upstream processing have substantially increased bioreactor yields, shifting the bioprocess bottlenecks towards the downstream processing. The work presented in this thesis aimed to develop new processes for adenoviruses puri cation. The use of state-of-the-art technology combined with innovative continuous processes contributed to build robust and cost-e ective strategies for puri cation of complex biopharmaceuticals.(...)

Digital microfluidics on paper

This thesis is one of the first reports of digital microfluidics on paper and the first in which the chip’s circuit was screen printed unto the paper. The use of the screen printing technique, being a low cost and fast method for electrodes deposition, makes the all chip processing much more aligned with the low cost choice of paper as a substrate. Functioning chips were developed that were capable of working at as low as 50 V, performing all the digital microfluidics operations: movement, dispensing, merging and splitting of the droplets. Silver ink electrodes were screen printed unto paper substrates, covered by Parylene-C (through vapor deposition) as dielectric and Teflon AF 1600 (through spin coating) as hydrophobic layer. The morphology of different paper substrates, silver inks (with different annealing conditions) and Parylene deposition conditions were studied by optical microscopy, AFM, SEM and 3D profilometry. Resolution tests for the printing process and electrical characterization of the silver electrodes were also made. As a showcase of the applications potential of these chips as a biosensing device, a colorimetric peroxidase detection test was successfully done on chip, using 200 nL to 350 nL droplets dispensed from 1 μL drops.

Automated quantitative analysis of MCC-IMS spectra

Ion Mobility Spectrometry coupled with Multi Capillary Columns (MCC -IMS) is a fast analytical technique working at atmospheric pressure with high sensitivity and selectivity making it suitable for the analysis of complex biological matrices. MCC-IMS analysis generates its information through a 3D spectrum with peaks, corresponding to each of the substances detected, providing quantitative and qualitative information. Sometimes peaks of different substances overlap, making the quantification of substances present in the biological matrices a difficult process. In the present work we use peaks of isoprene and acetone as a model for this problem. These two volatile organic compounds (VOCs) that when detected by MCC-IMS produce two overlapping peaks. In this work it’s proposed an algorithm to identify and quantify these two peaks. This algorithm uses image processing techniques to treat the spectra and to detect the position of the peaks, and then fits the data to a custom model in order to separate the peaks. Once the peaks are separated it calculates the contribution of each peak to the data.

Functional MRI of stimulus interference on auditory processing in normal listeners and tinnitus patients

We are constantly immersed in stimuli. Upon reaching our senses, stimuli are processed within various brain systems along various pathways into the brain, and eventually turned into a percept. However, there are percepts that do not result from responses to external source stimuli. A particular case of this situation is the auditory percept known as tinnitus. Tinnitus can be seen as a task-irrelevant auditory percept, commonly reported to interfere with normal daily tasks. This is known from reports made by tinnitus sufferers that refer to their phantom percept as distracting, and that it diverts their focus from the task-relevant stimuli.(...)

Visual and verbal processing effects on human memory

In this study in the field of Consumer Behavior, brand name memory of consumers with regard to verbal and visual incongruent and congruent information such as memory structure of brands was tested. Hence, four experimental groups with different constellations of verbal and visual congruity and incongruity were created to compare their brand name memory performance. The experiment was conducted in several classes with 128 students, each group with 32 participants. It was found that brands, which are presented in a congruent or moderately incongruent relation to their brand schema, result in a better brand recall than their incongruent counterparts. A difference between visual congruity and moderately incongruity could not be confirmed. In contrast to visual incongruent information, verbal incongruent information does not result in a worse brand recall performance.

Integration of speech-processing technologies into Activobank's client interaction process

This dissertation analyzes the possibilities of utilizing speech-processing technologies to transform the user experience of ActivoBank’s customers while using remote banking solutions. The technologies are examined through different criteria to determine if they support the bank’s goals and strategy and whether they should be incorporated in the bank’s offering. These criteria include the alignment with ActivoBank’s values, the suitability of the technology providers, the benefits these technologies entail, potential risks, appeal to the customers and impact on customer satisfaction. The analysis suggests that ActivoBank might not be in a position to adopt these technologies at this point in time.