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

Monoenergetic neutron reference fields are used in neutron metrology for the calibration of different neutron detectors, including dose rate meters. The International Standardization Organization ISO has composed guidelines and requirements for the production of narrow energy spread neutron fields using a particle accelerator. The objective of this Thesis was to investigate a target material that could be used to produce a monoenergetic neutron field by irradiating it with protons. A broader energy distribution was deemed satisfactory in regard to the initial phase of the station’s development, as significant modifications to the beamline would be necessary to acquire more precise beam current values and to achieve proton energies closer to the reaction threshold energy. The target material was chosen to be lithium fluoride (LiF) based on a literature review and Monte Carlo simulations. The simulations were executed with the proton energy of 2.5 MeV, which is close to the threshold energy of the 7Li(p, n)7Be reaction, and with the fixed energy 10 MeV of the IBA cyclotron used to conduct the experiment. The simulations were executed with the MCNP6 code, and the results were compared to those obtained from equivalent Geant4 simulations. The simulations suggested two wide peaks around 3 MeV and 0.6 MeV at the proton energy of 10 MeV. The irradiation experiment included two phases, one of which entailed the use of a shadow cone to estimate the number of scattered neutrons in the neutron yield. The maximum neutron fluence of (2.62 ± 0.78)∙109 s-1 was measured at the pop-up probe current of (8.3 ± 0.8) µA. Gamma spectrometry was utilized after the experiment to further evaluate the number of 7Li(p,n)7Be reactions taken place in the target by calculating the number of 7Be nuclei in the LiF plate. Altogether, lithium fluoride exhibits promising characteristics as a target material for accelerator-based monoenergetic neutron production, although its application demands further considerations regarding for instance, the decrement of the proton energy and the aiming and measurement of the proton beam. These results contribute to the future development of a neutron irradiation station at the University of Helsinki.

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.

Tietokonetomografialla (TT) on ollut jo usean vuosikymmenen ajan tärkeä asema lääketieteellisenä kuvantamismenetelmänä, jolla pystytään tuottamaan tarkkoja leikekuvia kehon rakenteista. TT on historiansa aikana muuttunut ja kehittynyt menetelmänä teknologisten harppausten ansiosta. Kuvauksista on tullut nopeampia ja entistä tarkempia. Kaksoisenergiatietokonetomografia (KETT) on yksi TT-kuvantamisen kehitysaskel, jonka teoreettiset perusteet ovat olleet jo pitkään tiedossa, mutta joka on vasta viime vuosikymmenenä saanut enemmän sovelluskohteita. KETT lisää TT-kuvauksen materiaalierottelukykyä, mikä mahdollistaa tarkemman diagnostiikan ja vähentää jatkotutkimusten tarvetta. Laajempi KETT:n kliininen käyttö vaatii kuitenkin toimintatapojen muutosta ja pysyvän laadunvalvontaprotokollan muodostamista. Tämän maisterintutkielman tarkoituksena oli auttaa laadunvalvonnan kehittämistä HUS:n Diagnostiikkakeskuksessa kartoittamalla KETT-kuvausten toimintaa, kuvausparametrien vaikutusta tuloksiin ja laitekohtaisia eroja. Työhön kuuluvat mittaukset suunniteltiin ja toteutettiin yhdessä HUS:n Diagnostiikkakeskuksen Meilahden Tornisairaalan radiologian yksikön kanssa. Kuvauksissa käytettiin Siemens Healthineersin valmistamia SOMATOM Definition Flash - ja SOMATOM Force -laitteita sekä KETT-kuvantamiseen soveltuvaa testikappaletta. Mittauksissa tutkittiin testikappaleen pystysuuntaisen asettelun vaikutusta kuvauksista saataviin tuloksiin, materiaalien elektronitiheyden ja efektiivisen järjestysluvun määritystarkkuutta, varjoaineena käytetyn jodin pitoisuuden määritystarkkuutta ja kuvauksen annostason merkitystä. Työssä käytetyllä menetelmällä määritettiin testikappaleen materiaalien koostumuksellisia eroja. Tutkimuksen avulla voitiin havaita jodipitoisuuden määrittämisen olevan haasteellisempaa hyvin pienillä alueilla, mutta halkaisijaltaan 5 mm:n kokoisilla alueilla määritystarkkuus oli jo kohtalainen. Potilaan oikeanlaisen keskityksen ja kuvanlaadun havaittiin olevan erityisen tärkeää pehmytkudoksia kuvattaessa. Laitteiden välisten erojen todettiin olevan merkittävämpää eri laitemallien välillä kuin samanmallisten laitteiden välillä. Laadunvalvonnassa tulee ottaa huomioon laitteiden kalibraatio, jotta laitteiden välisiä eroja pystytään vähentämään. Jatkossa mittauksia tulee toteuttaa lisää mittausten välisen toistettavuuden varmistamiseksi.

This thesis focuses on the initial measurements and development of a 1.5K target temperature cryostat to contain all quantum standards in the quantum metrological triangle. Currently, the cryostat can reach 4.2K end temperature with a cryocooler to liquefy helium for cooling experiments related to the quantum standards of SI-units which require 1.5K end temperature and the 1.5K cooling circuit is one of the research questions of the thesis for future development of the cryostat. Measurements included cooling cycles in a helium environment for liquefaction, as well as no load conditions. Results of the experimentation conclude that liquefaction was unsuccessful at this stage, but could be achieved with improved temperature control. The thesis is based on experimental work carried out in VTT technical research center of Finland, during the course of which the cryostat was progressively developed towards the future utility of combining experiments that realize the quantum standards of Ampere, voltage and resistance under a single low temperature experimental platform, the unified quantum standard cryostat.

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.

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.

In this project, poly(2-methyl-2-oxazoline)-block-poly(2-n-butyl-2-oxazine)-block-poly(2-methyl-2- oxazoline) (PMeOx-b-PnBuOzi-b-PMeOx) and poly(2-methyl-2-oxazoline)-block-poly(2-n-propyl-2- oxazine) (PMeOx-b-PnPrOzi) with block lengths of 35-20-35 and 100-100, respectively, were synthesized. When dispersed in water these thermoresponsive polymers aggregate into micellar aggregates or form hydrogels. Polymers were characterized with 1H-NMR, GPC, and DLS. Age-related macular edema and diabetic macular edema are the most common reasons for blindness in industrialized countries. The triamcinolone acetonide, a corticosteroid used to treat both of these macular edemas, was loaded into the polymeric micelles or hydrogel of synthesized polymers using the thin film method. The loading efficiency for a triblock copolymer ((PMeOx35-b-PnBuOzi20- b-PMeOx35) polymeric micelles was 4 % at the polymer/drug ratio of 10/4 and for a hydrogel (PMeOx100-b-PnPrOzi100) it was 48 % with the same polymer/drug ratio. The properties of the PMeOx100-b-PnPrOzi100 hydrogel formulations with the drug were studied with rheological measurements, DSC, DLS, and GPC of formulations. The formulation showed storage modulus of 3 kPa and the gelation temperature at 16 °C. From the DSC two glass transition temperatures were obtained, Tg1 at around 12 °C and Tg2 at around 74 °C. The particle size distribution of the formulation obtained with DLS showed that there were assumingly micelles or vesicles with a hydrodynamic radius between 20 and 80 nm. The drug release from the hydrogel formulation was studied with the dialysis membrane method and all the drug was released within 24 hours. Both copolymers formed quite unstable formulations with the drug. The results from this study gives information how polyoxazoline- and polyoxazine-based materials can be used to encapsulate and release corticosteroids, such as triamcinolone acetonide. To increase the drug loading capacity and to stabilize formulations, some surfactants for the drug could be tested in the future.

Radiation therapy is one of the key treatments for cancer, utilizing ionizing radiation to destroy cancer cells. Proton therapy uses high-energy proton beams since protons have a favorable depth-dose curve. Clinical proton beams must meet strict quality standards in order to maximise the efficacy of the treatment while ensuring the patient safety. Real-time knowledge of the beam’s intensity profile is essential for an accurate beam delivery. While gas-filled ionization chambers have traditionally been used as the standard beam monitor, the swift development of the beam delivery techniques demands for more accurate beam monitors. Semiconductor detectors potentially offer more accurate and efficient alternative for ionization chambers. In this study, the feasibility of using a silicon pixel detector in proton beams was investigated. The detector was originally designed for tracking minimum ionizing particles at the CMS experiment at CERN. Two experiments — one with an alpha source and one in a proton beam — were carried out to characterize the detector. The response to protons with different intensities and energies was investigated more closely in the proton beam. The results show that the detector response to different proton energies agrees with theoretical expectations. The saturation of the pixels limits measuring the full energy of the protons, however measuring the full energy is not essential in beam profile measurements. The detector also has a linear response to the beam intensity, although, the counting efficiency of the detector should be improved with new readout electronics. With different readout electronics, the detector might be a viable option for the beam profile measurements in clinical proton beams.

Lipid-based solid-fat substitutes (such as oleogels) structurally modified using ultrasonic standing waves (USW), have recently been shown to potentially increase oleogel storage-stability. To enable their potential application in food products, pharmaceuticals, and cosmetics, practical and economical production methods are needed compared to previous work, where USW treated oleogel production was limited to 50-500 µL. The purpose of this work is to improve upon the previous procedure of producing structurally modified oleogels via the use of USW by developing a scaled up and convenient approach. To this aim, three different USW chamber prototypes were designed and developed, with common features in mind to: (i) increase process volumes to 10-100 mL, (ii) make the sample extractable from the treatment chamber, (iii) avoid contact between the sample and the ultrasonic transducer. Imaging of the internal structure of USW treated oleogels was used as the determining factor of successful chamber design. The best design was subsequently used to produce USW treated oleogels, of which the bulk mechanical properties were studied using uniaxial compression tests, along with local mechanical properties, investigated using scanning acoustic microscopy. Results elucidated the mechanical behaviour of oleogels as foam-like. Finally, the stability of treated oleogels was compared to control samples using an automated image analysis oil release test. This work enables the effective mechanical-structural manipulation of oleogels in volumes of 10-100 mL, paving the way to possible large-scale lipid-based materials USW treatments.