Browsing by master's degree program "Materiaalitutkimuksen maisteriohjelma (Materials Research)"

Eye plaque radiotherapy is a treatment method of ocular tumors: A sealed radiation source is temporarily placed on the surface of the eye in day surgery. Compared to externally delivered conventional radiation treatments, more precisely targeted brachytherapy allows a higher dose in the target tissue while keeping the dose to healthy tissue relatively low. In Finland, all eye plaque treatments are centralised in Helsinki and brachytherapy of the eye is performed annually on approximately 70 patients. Patient specific anatomy takes into account determination of specific location and shape of the tumor in respect of radio-biologically critical structures of the eye. Until now, this has not been systematically modeled in dose calculation of eye plaque brachytherapy at HUS. The new version of Plaque Simulator, a 3D treatment simulation and modeling package for I-125, Pd-103, Ir-192 and Ru-106 plaque therapy of ocular tumors, enables importation and digitisation of patient imaging data (fundus imaging, CT and MRI) which consequently allows for systematically accurate estimation of dose distribution not only in the tumor but also in surrounding healthy tissues. The aim of this Master’s thesis is to prepare the new version of Plaque Simulator simulation and modeling package for clinical use in patient dose calculation at HUS. A comparison is done between the dose calculation method of the old and the new version of Plaque Simulator, and the dose calculation parameters as well as the plaque modeling parameters are reviewed. The function of the image-based dose calculation method is also tested with an anonymised patient treated for a tumor of a more peculiar shape. The absorbed dose to water on the central axis of the radiation source is measured experimentally for two individual I-125-seed along with Ru-106-CCB-, I-125-CCB-, and two I-125-COB-plaques. Experimental results are compared with the results obtained from Plaque Simulator. Individual I-125-seed is used to calibrate the detector at a distance of 10 mm, yielding to a calibration factor of 0.808. The use of the gold parameter in the dose calculation is justified, and a dosimetry modifier of Plaque Simulator is found to be 1.226 for I-125-plaques. Ru-106-plaque measurements are not calibrated, making them only relative. However, an excellent correspondence is observed between Ru-106-plaque dose calculations in Plaque Simulator and the manufacturer’s certificate. The measurements are normalized to the manufacturer’s certificate with a normalisation factor of 1.117.

Nanoformation of an active pharmaceutical ingredient (API) in controlled expansion of supercritical solution (CESS®) was studied in situ with a schlieren imaging technique in wide range of pre-expansion and expansion conditions, involving pressures up to 1000 bars. The optical methods allowed measurements on solvent state in the first micro and milliseconds of the expansion. Quantitative values on jet shape and solvent thermodynamic state were obtained for different nozzle configurations. These values, combined with mathematical modelling, enabled tracking the nanoparticle formation along the flow. We also report on the importance of solvent phase behavior demonstrated by three fundamentally different expansion schemes: supercritical (SC) to liquid/gas, SC to gas/liquid, and SC to SC. Scanning electron microscope images of the nanosized API are presented. This shows that one can have controlled particle formation by altering the thermodynamic conditions at the nozzle and changing the expansion path. The results guide the in-house process optimization and offer insight into the physics of supercritical fluid processing.

Nanodiscs are a synthetic model system for studying the behavior of cell membranes. They are used in experimental biological research to understand structural and functional properties of membrane proteins. Their utility is chiefly due to their water solubility and a relative native lipid environment for membrane proteins compared to other synthetic membrane systems. Though membrane proteins are frequently solubilized and stabilized in a nanodisc environment, the physical conditions that they are exposed to in a nanodisc have not been studied in detail. Additionally, the dynamic behavior of transmembrane proteins in a nanodisc environment has not been characterized with respect to a more typical planar bilayer environment. The results presented in this thesis formulate an answer to these open questions through atomistic molecular dynamics simulations and machine learning methods. Nanodiscs and bilayer systems with identical lipid compositions are systematically studied, and separately, both types of systems with adenosine receptor A2AR to understand the differences between the model systems. The membrane environment in the two systems is characterized by two well understood physical properties: the order parameter, and the diffusion of lipids in the membrane. The results not only affirm previous studies of nanodiscs but also provide novel insights into the membrane environment of the nanodisc systems. Finally, with the help of machine learning methods, the dynamical behaviour of the protein is shown to be significantly altered in the nanodisc system when compared to a planar bilayer environment. Specifically, it is shown that the activation behavior of A2AR is dependent on model system used to reconstitute the protein.

Monienerginen röntgensäde kokee kovenenemista aineessa. Yleisimmin röntgenpaneelien kalibroinnissa käytetty flat-field (FF)-korjaus on riittämätön säteen kovenemisen aiheuttamien kuvavääristymien korjaamiseen. Signal-to-thickness Calibration (STC)-menetelmässä kuvataan useita paksuuksia väliainetta ja luodaan pikselikohtainen sovitus säteen havaitun intensiteetin ja väliaineen välillä.Tämä sovitus ottaa sekä pikselikohtaiset vaste-erot, että säteen kovenemisen huomioon. Tässä tutkimuksessa arvioitiin STC-menetelmän kykyä parantaa kuvanlaatua verrattuna FF-korjattuun rekonstruktioon käyttäen kliinistä pään alueen kartiokeilatomografialaitetta. Kalibrointimateriaalina toimi akryylimuovi (PMMA). Kuvanlaatua arvioitiin kontrastin, kontrasti-kohina-suhteen, paikallisen kohinan ja cupping-ilmiön voimakkuuden sekä rengaskuvavääristymien arvioinnin avulla. Tutkimus avaa STC-menetelmän toimivuutta eri kudoskohteille hyväksikäyttäen fantomia ja kudosekvivalentteja materiaaleja. Tutkimuksessa tarkasteltiin sekä kovia että pehmeitä kudoksia. Kovina kudoksina käytettiin neljää eri konsentraatiota kalsiumhydroksiapatiittia (CaHA) sekä kolmea konsentraatiota jodia. Pehmeitä kudosekvivalentteja materiaaleja olivat aivot, imusolmukkeet, veri,rasvakudos, maksa, keuhko ja lihas. Fantomina toimi QRM Spectral Phantom II. Kun vertaillaan STC-korjattuja rekonstruktioita FF-korjattuihin, sekä kontrastin että kontrasti-kohina-suhteen havaittiin paranevan noin 27-30% aivo-, imusolmuke- ja lihaskudoksilla. Suurin kasvu tapahtui 80 kV:n putkijännitteellä. Ainoa kudosekvivalentti materiaali, jolle ei havaittu systemaattista kontrastin paranemista oli rasvakudos. Muissa pehmeissä kudoksissa kasvua tapahtui n.5%:sta 20%:iin. Koville kohtioille STC-menetelmän havaittiin myös kohentavan kontrastia n.4% - 9%. Cupping-ilmiön voimakkuuden heikkenemistä havaittiin systemaattisesti kaikilla kuvausparametreilla. Suurin heikkeneminen tapahtui kuitenkin intuitiivisesti matalimmalla putkijännitteellä 80 kV. Rengaskuvavääristymien voimakkuutta arvioitiin subjektiivisesti, eikä niiden havaittu heikkenevän merkittävästi. Tulokset antavat viitteitä kohenneesta pehmeän kudoksen kontrastista, joka on yksi suurimmista rajoittavista tekijöistä kartiokeilatietokonetomografiassa. Kudosten HU-arvoissa päästiin STC-korjatuilla rekonstruktoilla lähemmäksi todellisia kudosten HU-arvoja.

Lentoaika-rekyylispektrometria (TOF-ERDA) on materiaalin tutkimusmenetelmä, minkä avulla kyetään selvittämään näytteen alkuainepitoisuudet syvyyden funktiona. Menetelmässä on huomattu esiintyvän systemaattista poikkeamaa teoriasta. Poikkeaman syy on toistaiseksi epäselvä. Tutkielmassa tutkittiin poikkeaman syytä sekä suuruutta. Tutkimiseen käytettiin Helsingin yliopiston kiihdytinlaboratorion 5 MV EPG-10-II-tandemkiihdyttimeen liitettyä TOF-ERDA-laitteistoa. Laitteistolla tutkittiin ilmiön esiintymistä eri hiukkasilla, eri energioilla ja eri näytteillä. Kokeiden tuloksia verrattiin teorian ehdottamiin tuloksiin. Suurimmat poikkeamat kokeiden ja teorian välillä esiintyi pienienergisillä ja keveillä ammusioneilla, kun tutkittiin raskasalkuaineista näytettä. Kokeissa käytettyjen hiukkasten sirontaa TOF-ERDA-laitteiston lentoaikaporteista selvitettiin simuloinneilla. Simulointityökaluna työssä käytettiin SRIM-ohjelmistoa. Simulointien pohjalta hiukkasille laskettiin korjauskertoimet. Korjauskertoimen suuruuden huomattiin olevan riippuvainen hiukkasen energiasta sekä järjestysluvusta. Korjauskertoimista luotiin malli, jonka avulla kyetään arvioimaan ja korjaamaan kokeissa tapahtuvaa sirontaa lentoaikaporteista. Myös varjostumisen vaikutusta tuloksiin tutkittiin. Varjostumista tutkittiin jo olemassa olevan Andersenin mallin avulla. Andersenin mallin mukaan varjostumisen vaikutus tuloksiin on hyvin vähäistä sekä ilmiötä pienentävää, ei ilmiötä selittävää. Huomioitavaa kuitenkin on mallin soveltumattomuus kyseisiin vuorovaikutuksiin, täten varjostumisen vaikutusta ilmiöön ei voida kokonaan poissulkea. Tutkielman tulokset valottavat TOF-ERDA:n systemaattisen poikkeaman syitä. Lentoaikaporttisironnan vaikutus tuloksiin on merkittävä, selittäen noin puolet ilmiöstä. Tulosten pohjalta luotu malli on voimassa vain kyseiselle TOF-ERDA-laitteistolle, sillä sironnan suuruus on riippuvainen lentoaikaporttien materiaalista, paksuuksista sekä laitteiston geometriasta. Kuitenkin mille tahansa TOF-ERDA-laitteistolle on mahdollista luoda vastaava malli, noudattamalla tämän tutkielman prosesseja. Jäljelle jäävän selittämättömän poikkeaman huomattiin olevan myös riippuvainen energiasta sekä järjestysluvuista. Tämä viittaisi jäljelle jäävän poikkeaman aiheutuvan mahdollisesta monikertasironnasta näytteessä, ja tai varjostumisesta, jota Andersenin malli ei kykene huomioimaan.

In the field of cryogenics and superconducting technology, the effect of eddy currents presents a significant challenge, as large inductive currents can affect the performance and stability of cryogenic components. In our work, we examine how the magnitude of eddy current effects varies with different samples when placed within a changing magnetic field. In high magnetic field applications, any deviation in the magnetic field induces currents within low-resistivity components, leading to eddy current heating and Lorentz forces. This thesis focuses on how to simulate the eddy current phenomena in an accurate way through methods of finite element analysis, utilizing the commercial software of COMSOL Multiphysics. To provide a comprehensive simulation of the effects of eddy currents, our work involves the coupling of three distinct physical fields: solid mechanics, heat transfer, and electromagnetic fields. To solve multiphysical problem in an efficient way, we explain different strategies on how the coupled fields can be solved in a simplified, but effective way. The simulation was examined for two different time scale scenarios: 1. Turning on the magnet, where the time scale of the phenomena is in the order of several hours, and 2. The more demanding scenario of the quench of a superconducting magnet, where the time scale is in the order of several seconds. We found that during the ramping of the magnet the electromagnetic heating of the sample can reach the scales of milliwatts, which is significant head load in a cryogenic setting. During magnet quench, we found that the Lorentz forces can reach up to scales of kilonewtons. The results indicate that the volume of the sample has significant impact to effects of eddy currents, but when considering the magnitude of the Lorentz force the length and spatial location of the sample has significant effect. Hence, it is crucial to pay attention to the appropriate design of the sample that is placed into the magnetic field.

Scanning probe microscopy (SPM), which includes atomic force microscopy (AFM), is an affordable and powerful tool for investigating surfaces. However, to ensure accuracy, a metrologically informed approach is required. In this thesis, a commercial Jupiter XR AFM was used for calibration experiments testing its reliability and accuracy. AFMs can further be improved by the use of active probes with added capabilities that allow for faster scanning speeds and other improvements. Efforts have been made to enable their broader use. At VTT MIKES, the commercial Jupiter XR AFM is being modified to use active probes capable of self-sensing and self-actuation. A simple AFM was first built as a test setup to better understand the probes and to split their integration into the Jupiter AFM into a step-by-step process where the mechanical, electronic, and software changes necessary could be separated into distinct parts. In this thesis, I describe experiments done to test the reliability of the commercial AFM, and the process of constructing and using the test setup AFM, after which I present some results obtained using them, and discuss the experiments and the integration process. Included is also an overview of metrology and some of the physics and other theory relevant to AFM, and a summary of the principles of AFM and its role in microscopy. This work is part of the MetExSPM project, which seeks to develop traceable high speed scanning probe microscopy, for example by achieving higher scanning speeds and larger scanning areas, while maintaining good resolution and metrologically traceable high accuracy. This will greatly increase the utility of SPMs, especially for industrial applications.

Imaging done with conventional microscopes is diffraction-limited, which sets a lower limit to the resolution. Features smaller than the resolution cannot be distinguished in images. This limit of the diffraction-limit can be overcome with different setups, such as with imaging through a dielectric microcylinder. With this setup it is possible to reach smaller resolution than with a diffraction-limited system, which is called super-resolution. Propagation of light can be modelled with various simulation methods, such as finite-difference time-domain and ray tracing methods. Finitedifference time-domain method simulates the light as waves which is useful for modelling the propagation of light accurately and take into account the interactions between different waves. Ray tracing method simulates the light as rays which requires approximations to the light’s behaviour. This means that some phenomena cannot be taken into account, which can affect the accuracy of the results. In this thesis the model for simulating super-resolution imaging with microcylinder is studied. The model utilizes the finite-difference timedomain method for modelling the near-field effects of the light propagating through the microcylinder and reflecting back from a sample. The reflected light is recorded on the simulation domain boundaries and a near-field-to-far-field transformation is performed to obtain the far-field corresponding to the recorded fields. The far-field is backward propagated to focus a virtual image of the sample, and the virtual image is then used in ray tracing simulation as a light source to focus it to a real image on a detector.

Energy is an essential input for any non-spontaneous mechanism. In biological organisms, the process of producing energy currency, adenosine triphosphate, is called cellular respiration. It is made of three smaller steps, out of which the last one is oxidative phosphorylation that is responsible for the largest production of adenosine triphosphate molecules in the whole process. Oxidative phosphorylation is performed by the electron transport chain made of five protein complexes, named respiratory complex I-V. Complex I is the first and largest protein complex in the electron transport chain, and it is the least understood. Its primary function is to transfer electrons from nicotinamide adenine dinucleotide to ubiquinone, which is coupled to the pumping of four protons across the mitochondrial inner membrane. Although the overall reaction of complex I is understood, the intricate detail of the mechanism is still largely unknown. There is significance in the details because there are numerous point mutations, which have been strongly correlated with neurogenerative diseases, such as Leigh’s syndrome, and aging. Therefore, a more thorough understanding of its mechanism can give insight into potential target drug development. Complex I is made of 14 highly conserved subunits that can be found in most species that use the electron transport chain. They create an L-shape, where seven subunits are embedded in the inner membrane, the membrane domain, and the others are floating in the mitochondrial matrix, the peripheral arm. In mitochondrial complex I, however, there are in addition around 30 accessory subunits. It has been previously thought that the main mechanism is conducted by the 14 subunits that are found in all species. However, in the past couple of years, it has been shown that accessory subunits can play an important role in the mechanism of mitochondrial complex I. The work presented in this thesis uses a multiscale computational approach to study the effect of three mutations, F89A, Y43A and L42A, from an accessory subunit LYRM6 on the function of complex I. Previous experiments demonstrated that the mutations decreased the overall activity of complex I by 76-86 %. The LYRM6 subunit is located at the pivot of the membrane and periplasmic domains. The results of this study show that the point mutations have a long-range effect on the conformations of three loops from three conserved subunits in this region. The shift in the loop dynamics causes a drop in water occupancy. The observed water pathway is tested for the capability of proton transfer. The findings are demonstrated with the help of molecular dynamics and quantum mechanics/molecular mechanics simulations.

Ensuring adequate air quality is integral to healthy living. Since in modern societies the majority of time is spent indoors, understanding indoor air pollution and the means of air purification are of great importance. Adverse health effects are induced by volatile organic compounds (VOC) that originate from everyday activities and our surroundings. Photocatalysis is a radiation-activated chemical transformation that can be used to decompose organic pollutants into harmless constituents. However, existing air purification solutions employing photocatalysis often rely on UV light limiting the use of solar radiation. Titanium dioxide is a popular photocatalyst material, but it requires modification to its electronic properties to respond to visible light. An established approach is to introduce atoms of other dopant elements into the titania lattice. Atomic layer deposition (ALD) is a thin film deposition technique widely studied especially in metal and metal oxide research. Following from the principle of sequential saturation of the surface, control over the size and composition of the film may reach atomic level. Since the chemical configuration of a doped TiO2 film is of utmost importance to successful modification, ALD is an excellent tool to examine suitable photocatalytic TiO2 chemistries. Furthermore, thin solid films of catalytically active material would have a distinguished advantage for deployment in real-life settings over their powderous counterparts. The literature review of this thesis explores the semiconductor photocatalysis with an eye on its suitability to indoor air purification. The motivation is to give the reader a view on the air quality issue, the existing technological solutions and how a thin film photocatalyst could supplement the field. Titanium dioxide doping concepts are introduced to elucidate the rationale behind the experimental efforts. The experimental part describes a development project to deposit visible-light responding photocatalysts. Titanium dioxide thin films co-doped with nitrogen and zinc/fluorine were grown on steel plates. An in-house built reactor system was used to study acetaldehyde degradation under irradiation. Unfortunately, the reactor experienced a malfunction, rendering a large part of the results futile. Moreover, months of valuable time were lost in chasing a mirage of fallacious data. In the end an ALD grown photocatalyst responding to visible light could not be materialized.