Optimisation of chemical lysis protocol for point-of-care leukocyte differentiation

The full blood cell (FBC) count is the most common indicator of diseases. At present hematology analyzers are used for the blood cell characterization, but, recently, there has been interest in using techniques that take advantage of microscale devices and intrinsic properties of cells for increased automation and decreased cost. Microfluidic technologies offer solutions to handling and processing small volumes of blood (2-50 uL taken by finger prick) for point-of-care(PoC) applications. Several PoC blood analyzers are in use and may have applications in the fields of telemedicine, out patient monitoring and medical care in resource limited settings. They have the advantage to be easy to move and much cheaper than traditional analyzers, which require bulky instruments and consume large amount of reagents. The development of miniaturized point-of-care diagnostic tests may be enabled by chip-based technologies for cell separation and sorting. Many current diagnostic tests depend on fractionated blood components: plasma, red blood cells (RBCs), white blood cells (WBCs), and platelets. Specifically, white blood cell differentiation and counting provide valuable information for diagnostic purposes. For example, a low number of WBCs, called leukopenia, may be an indicator of bone marrow deficiency or failure, collagen- vascular diseases, disease of the liver or spleen. The leukocytosis, a high number of WBCs, may be due to anemia, infectious diseases, leukemia or tissue damage. In the laboratory of hybrid biodevices, at the University of Southampton,it was developed a functioning micro impedance cytometer technology for WBC differentiation and counting. It is capable to classify cells and particles on the base of their dielectric properties, in addition to their size, without the need of labeling, in a flow format similar to that of a traditional flow cytometer. It was demonstrated that the micro impedance cytometer system can detect and differentiate monocytes, neutrophils and lymphocytes, which are the three major human leukocyte populations. The simplicity and portability of the microfluidic impedance chip offer a range of potential applications in cell analysis including point-of-care diagnostic systems. The microfluidic device has been integrated into a sample preparation cartridge that semi-automatically performs erythrocyte lysis before leukocyte analysis. Generally erythrocytes are manually lysed according to a specific chemical lysis protocol, but this process has been automated in the cartridge. In this research work the chemical lysis protocol, defined in the patent US 5155044 A, was optimized in order to improve white blood cell differentiation and count performed by the integrated cartridge.

Analysis and optimisation of books flow among branches through simulation: the case of Trondheim’s Public Library

Il presente lavoro di tesi verte sull’analisi e l’ottimizzazione dei flussi di libri generati tra le diverse sedi della biblioteca pubblica, Trondheim folkebibliotek, situata a Trondheim, città del nord norvegese. La ricerca si inserisce nell’ambito di un progetto pluriennale, SmartLIB, che questa sta intraprendendo con l’università NTNU - Norwegian University of Science and Technology. L’obiettivo di questa tesi è quello di analizzare possibili soluzioni per ottimizzare il flusso di libri generato dagli ordini dei cittadini. Una prima fase di raccolta ed analisi dei dati è servita per avere le informazioni necessarie per procedere nella ricerca. Successivamente è stata analizzata la possibilità di ridurre i flussi andando ad associare ad ogni dipartimento la quantità di copie necessarie per coprire il 90% della domanda, seguendo la distribuzione di Poisson. In seguito, sono state analizzate tre soluzioni per ottimizzare i flussi generati dai libri, il livello di riempimento dei box ed il percorso del camion che giornalmente visita tutte le sedi della libreria. Di supporto per questo secondo studio è stato il Vehicle Routing Problem (VRP). Un modello simulativo è stato creato su Anylogic ed utilizzato per validare le soluzioni proposte. I risultati hanno portato a proporre delle soluzioni per ottimizzare i flussi complessivi, riducendo il delay time di consegna dei libri del 50%, ad una riduzione del 53% del flusso di box e ad una conseguente aumento del 44% del tasso di riempimento di ogni box. Possibili future implementazioni delle soluzioni trovate corrispondono all’installazione di una nuova Sorting Machine nella sede centrale della libreria ed all’implementazione sempre in quest’ultima di un nuovo schedule giornaliero.

Regularization methods for the solution of a nonlinear least-squares problem in tomography

In this work we study a polyenergetic and multimaterial model for the breast image reconstruction in Digital Tomosynthesis, taking into consideration the variety of the materials forming the object and the polyenergetic nature of the X-rays beam. The modelling of the problem leads to the resolution of a high-dimensional nonlinear least-squares problem that, due to its nature of inverse ill-posed problem, needs some kind of regularization. We test two main classes of methods: the Levenberg-Marquardt method (together with the Conjugate Gradient method for the computation of the descent direction) and two limited-memory BFGS-like methods (L-BFGS). We perform some experiments for different values of the regularization parameter (constant or varying at each iteration), tolerances and stop conditions. Finally, we analyse the performance of the several methods comparing relative errors, iterations number, times and the qualities of the reconstructed images.

Catalytic decomposition of formic acid using supported metal nanoparticles

Upgrade of hydrogen to valuable fuel is a central topic in modern research due to its high availability and low price. For the difficulties in hydrogen storage, different pathways are still under investigation. A promising way is in the liquid-phase chemical hydrogen storage materials, because they can lead to greener transformation processes with the on line development of hydrogen for fuel cells. The aim of my work was the optimization of catalysts for the decomposition of formic acid made by sol immobilisation method (a typical colloidal method). Formic acid was selected because of the following features: it is a versatile renewable reagent for green synthesis studies. The first aim of my research was the synthesis and optimisation of Pd nanoparticles by sol-immobilisation to achieve better catalytic performances and investigate the effect of particle size, oxidation state, role of stabiliser and nature of the support. Palladium was chosen because it is a well-known active metal for the catalytic decomposition of formic acid. Noble metal nanoparticles of palladium were immobilized on carbon charcoal and on titania. In the second part the catalytic performance of the “homemade” catalyst Pd/C to a commercial Pd/C and the effect of different monometallic and bimetallic systems (AuxPdy) in the catalytic formic acid decomposition was investigated. The training period for the production of this work was carried out at the University of Cardiff (Group of Dr. N. Dimitratos).

A multi-objective genetic algorithm optimisation using variable speed pumps in water distribution systems

Due to its practical importance and inherent complexity, the optimisation of distribution networks for supplying drinking water has been the subject of extensive study for the past 30 years. The optimization is governed by sizing the pipes in the water distribution network (WDN) and / or optimises specific parts of the network such as pumps, tanks etc. or try to analyse and optimise the reliability of a WDN. In this thesis, the author has analysed two different WDNs (Anytown City and Cabrera city networks), trying to solve and optimise a multi-objective optimisation problem (MOOP). The main two objectives in both cases were the minimisation of Energy Cost (€) or Energy consumption (kWh), along with the total Number of pump switches (TNps) during a day. For this purpose, a decision support system generator for Multi-objective optimisation used. Its name is GANetXL and has been developed by the Center of Water System in the University of Exeter. GANetXL, works by calling the EPANET hydraulic solver, each time a hydraulic analysis has been fulfilled. The main algorithm used, was a second-generation algorithm for multi-objective optimisation called NSGA_II that gave us the Pareto fronts of each configuration. The first experiment that has been carried out was the network of Anytown city. It is a big network with a pump station of four fixed speed parallel pumps that are boosting the water dynamics. The main intervention was to change these pumps to new Variable speed driven pumps (VSDPs), by installing inverters capable to diverse their velocity during the day. Hence, it’s been achieved great Energy and cost savings along with minimisation in the number of pump switches. The results of the research are thoroughly illustrated in chapter 7, with comments and a variety of graphs and different configurations. The second experiment was about the network of Cabrera city. The smaller WDN had a unique FS pump in the system. The problem was the same as far as the optimisation process was concerned, thus, the minimisation of the energy consumption and in parallel the minimisation of TNps. The same optimisation tool has been used (GANetXL).The main scope was to carry out several and different experiments regarding a vast variety of configurations, using different pump (but this time keeping the FS mode), different tank levels, different pipe diameters and different emitters coefficient. All these different modes came up with a large number of results that were compared in the chapter 8. Concluding, it should be said that the optimisation of WDNs is a very interested field that has a vast space of options to deal with. This includes a large number of algorithms to choose from, different techniques and configurations to be made and different support system generators. The researcher has to be ready to “roam” between these choices, till a satisfactory result will convince him/her that has reached a good optimisation point.

Morphological and optical properties of SiON thin films for photovoltaic applications

In the last years technologies related to photovoltaic energy have rapidly developed and the interest on renewable energy power source substantially increased. In particular, cost reduction and appropriate feed-in tariff contributed to the increase of photovoltaic installation, especially in Germany and Italy. However, for several technologies, the observed experimental efficiency of solar cells is still far from the theoretical maximum efficiency, and thus there is still room for improvement. In this framework the research and development of new materials and new solar devices is mandatory. In this thesis the morphological and optical properties of thin films of nanocrystalline silicon oxynitride (nc-SiON) have been investigated. This material has been studied in view of its application in Si based heterojunction solar cells (HIT). Actually, a-Si:H is used now in these cells as emitter layer. Amorphous SiO_x N_y has already shown excellent properties, such as: electrical conductivity, optical energy gap and transmittance higher than the ones of a-Si:H. Nc-SiO_x N_y has never been investigated up to now, but its properties can surpass the ones of amorphous SiON. The films of nc-SiON have been deposited at the University of Konstanz (Germany). The properties of these films have been studied using of atomic force microscopy and optical spectroscopy methods. This material is highly complex as it is made by different coexisting phases. The main purpose of this thesis is the development of methods for the analyses of morphological and optical properties of nc-SiON and the study of the reliability of those methods to the measurement of the characteristics of these silicon films. The collected data will be used to understand the evolution of the properties of nc-SiON, as a function of the deposition parameters. The results here obtained show that nc-SiON films have better properties with respect to both a-Si:H and a-SiON, i. e. higher optical band-gap and transmittance. In addition, the analysis of the variation of the observed properties as a function of the deposition parameters allows for the optimization of deposition conditions for obtaining optimal efficiency of a HIT cell with SiON layer.

Development of an impedance based biosensor for studies of spheroids formation

Three-dimensional (3D) multicellular spheroids are exceptional in vitro cell models for their ability to accurately mimic real cell-cell interaction processes. However, the challenges in producing well-defined spheroids with controlled size together with the deficiency of techniques to monitor them significantly restrict their use. Herein, a novel device to study spheroid formation in real time is presented. By exploiting electrochemical impedance spectroscopy, a multi-electrode array (MEA) attached to a calcium alginate scaffold is able to monitor the behaviour of 36 different hydrogel wells. The scaffold contains inverted shape pyramidal microwells, which guide the aggregation of cells into spheroids with controlled dimensions. Preliminar studies on calcium alginate, optimisation of fabrication strategy are shown, together with testing of the device in the presence and the absence of the hydrogel. Lastly, the device was tested for its intended aim, i.e. to monitor the formation of a spheroid, proving its potential as an impedance biosensor.