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Poli(4-klor naftil metakrilat)Na-montmorillonit nanokompozitlerin sentezi ve karakterizasyonu
Bu çalışmada, 4-Klor Naftil Metakrilat monomeri, 4-Klor Naftol ile Metakriloilklorür'ün Trietilaminli (NR3) ortamdaki reaksiyonundan sentezlenmiştir. 4-Klor Naftil Metakrilat monomerinin sodyum montmorillonit kil mineraliyle oluşturduğu kompozitleri sentezlenmiş ve karakterizasyonu yapılmıştır. Kompozitlerin sentezi; kilin saflaştırılması ve katyon değişim kapasitesinin belirlenmesi(KDK), organokil sentezi ve nanokompozit sentezi olmak üzere üç aşamada gerçekleştirilmiştir. Saf kil kurutularak KDK tayini yapılmış ve organokil sentezinde kullanılmıştır. Kilin KDK değeri ANSI/ASTM C837-76 standardına göre belirlenmiştir. Organokil sentezinde; uzun zincirli dimetil n-oktadesil amonyum klorür yüzey aktif madde kullanılmıştır. Sentezlenen organokil ve nanokompozitlerin tabakalar arası uzaklıkları X-Işını Kırınımı (XRD) analizleri ile belirlenmiştir. Nanokompozit sentezi yerinde (in-situ) polimerizasyonla yapılmış ve kütlece %33, %46 ve %67 kil içeren nanokompozitler; XRD, termogravimetrik analiz (TGA), atomik güç mikroskobu (AFM) ve taramalı elektron mikroskobu (SEM) analizleriyle karakterize edilmişlerdir.
Basınçlı infiltrasyon yöntemi ile üretilen AA2024 ve AA6061 matrisli, B4C ve SiC takviyeli kompozitlerin üretimi içyapı, fiziksel ve mekanik özelliklerin incelenmesi
Bu çalışmada, %50 oranlarında B4C ve SiC partikül takviyeli AA2024 ve AA6061 matrisli kompozit malzemelerin mikroyapı ve mekanik özelliklerine matris bileşimi ve basınç değerinin etkisi incelenmiştir. Çelik borular içerisine 50x8 mm ölçülerinde 48μm ortalama tane boyutuna sahip B4C tozları veya 37μm ortalama tane boyutuna sahip SiC tozları kullanılarak preformlar oluşturulmuştur. Hazırlanan preformlara, 800oC'de basınçlı infiltrasyon tekniği kullanılarak 7 bar ve 8 bar basınçlarda AA2024 ve AA6061 alüminyum matrisler infiltre edilmiştir. Üretilen kompozit malzemelerin mikroyapı incelemeleri EDS donanımlı taramalı elektron mikroskobu (SEM) kullanılarak gerçekleştirilmiştir. Porozite hesabı hassas teraziye entegre alkol içerisinde askı aparatlı cihaz kullanılarak yapılmıştır. Kompozit malzemelerin mikroyapı incelemeleri, porozitelerin B4C ve SiC takviye partiküllerinin çevresinde yoğunlaşarak meydana geldiği görülmüştür. Artan basınç miktarlarıyla porozite hacim oranında düşüş sağlanmıştır. Elde edilen görüntülerde SiC partiküllü kompozit malzemelerin B4C partiküllü kompozitlere göre daha çok poroziteye sahip olduğu görülmektedir. Bunun sebebinin ise toz tane boyutundan kaynaklandığı görülmektedir. Kompozit malzemelerinin EDS analizlerinde gri renkte intermetaliklerin oluştuğu tespit edilmiştir. Matris elemanında değişen takviye elamanı ile oluşan yapısal farklılıkların tayininde X-Işını difraksiyonu (XRD) kullanılmıştır. XRD analizinde kompozit malzemelerde Al4C3, Al3Ti, Al3BC, Al4SiC4, Al2O3, Al4C3, Mg2Cu, Al3Cu2, MgCuAl2, CuAl2, Al6Si2O13, Al2O3 ve Mg2Si gibi ikincil fazlar oluştuğu gözlemlenmiştir. Mekanik özellikler sertlik ve basma deneyleri ile belirlenmiştir. AA2024 veya AA6061 matrisli kompozit malzemelerin sertlik deneylerinde B4C veya SiC takviyeli kompozitlere uygulanan basınç değerlerinin artması ile sertlik değerinde büyük oranında artış gözlemlenmiştir. Basma deneyinde AA2024 veya AA6061 matrisli kompozit malzemelere takviye elemanı olarak kullanılan B4C veya SiC takviyelerine uygulanan basınç değerinin arttırılmasıyla basma mukavemetlerinin de arttığı gözlemlenmiştir. Bu durum sertlik sonuçlarıyla da uyumludur. Üretilen bu kompozitlerin basma mukavemetindeki bu artış porozitedeki %90'lara varan oranlardaki düşüş ve yapılarda meydana gelen ikincil fazların etkisidir. Yapılan karşılaştırmalara göre mekanik özelliklerdeki iyileşmeler basınç miktarı artması ile özelliklerin arttığı gözlemlenmiştir. Matris elemanı açısından kıyaslama yapıldığında AA6061 matrisli kompozit malzemelerin, AA2024 matrisli kompozit malzemelere göre daha iyi mekanik özelliklere sahip olduğu gözlemlenmiştir. Ayrıca takviye elemanları açısından kıyaslama yapıldığında ise B4C takviyeli kompozit malzemelerin, SiC takviyeli kompozit malzemelere göre daha iyi mikroyapı ve mekanik özelliklere sahip olduğu gözlemlenmiştir.
Krank kasnağına etki eden titreşimleri sönümlemek üzere kullanılan elastomer yapının, nano-malzemeler ile iyileştirerek mekanik davranışlarının deneysel ve sonlu elemanlar yöntemiyle incelenmesi
Ülkemizde gelişmekte olan otomotiv ve savunma sanayisine ilgi gün geçtikçe artmaktadır. Teknolojinin ilerlemesi bu sektörlerde kullanılan ürünlerin mühendislik tasarımlarıyla malzeme kullanımının ne kadar önemli olduğunu göstermektedir. Bu çalışmada doğal kauçuk ve EPDM kauçuğa homojen karıştırma, püskürtme ve el yatırma kompozit üretim yöntemleri kullanılarak çok duvarlı karbon nano tüpü, nano parçacıklı alümina ve nano parçacıklı zeolit takviye edilmiştir. Elde edilen numuneler reolojik, termal ve mekanik testlere tabi tutulmuştur. Yapılan bu çalışma verileri ile krank milinin matematiksel modellemesi çıkarılarak, modal analiz ile doğal frekansları ve mod şekilleri sonlu elemanlar yöntemi kullanılarak bulunmuştur. Krank milinde ortaya çıkan radyal ve burulma titreşimlerini absorbe etmek için bir krank kasnağı tasarlanmıştır. Krank kasnağının dayanımı deneysel verilerden elde edilen bilgiler ile sonlu elemanlar yöntemi kullanılarak hata oranı çıkarılmıştır. Krank kasnağının rezonans durumunda ki doğal frekansları FFT analizi ile bulunduktan sonra sonlu elemanlar programı kullanılarak modal analiz yöntemi ile doğrulanmaya gidilmiştir. Titreşim sönümleyen altı farklı kasnak motor simülasyon testine tabi tutulmuş ve akustik kontrollerden geçmiştir. Bu çalışmaların sonucunda, titreşim sönümlemesi açısından en iyi homojen karıştırılmış karbon tüpü takviyeli EPDM kauçuktan oluşan krank kasnağı olduğu bulunmuştur.
Doku benzeri fantomların fotoakustik görüntülenmesi için cmut dizin yongaların ölçeklenebilir mikro üretimi (2. bölüm)
In this thesis study, Capacitive Micromachined Ultrasound Transducer (CMUT) array chips are microfabricated with wafer-scale batch-compatible approaches as sensors for photoacoustic imaging (PAI) applications. Photoacoustic imaging (PAI) is a non-invasive medical imaging technology, free from X-ray radiation, that utilizes contrast data resulting from acoustic detection of optical stimulation to construct images. CMUT array devices are microelectromechanical systems (MEMS) devices that generate or detect acoustic or pressure waves within the ultrasonic frequency range. The CMUT devices function on the principle of vibrating parallel plate variable capacitors. Capacitance variations due to vibrating plate electrode create electrical current signals in CMUT cells, which are further processed to obtain meaningful results. In PAI, pulsed laser light is transmitted and absorbed by naturally occurring photo-absorber compounds or contrast agents in selective body-tissue or tissue-like materials. The laser pulses are converted into heat, resulting in thermoelastic expansion vibrations of the tissue or tissue-like materials (i.e., phantom material). These vibrations travel as pressure or acoustic waves through the tissue or tissue-like materials that may be detected by CMUT sensors. For the production of the CMUT array devices, borosilicate glass (Pyrex-7740) wafers were selected as transparent substrates. The bottom electrode and electrical insulation layer above the bottom electrode of the CMUT sensors are processed on the Pyrex substrates. Anodic wafer bonding is selected as one of the suitable CMUT gap formation and top electrode integration technologies. Clean and unprocessed SOI (silicon-on-insulator) wafers are used for the formation of the top electrode of the CMUT sensors. The silicon handle layer and buried oxide (SiO2) layer of the SOI wafer are removed in order to reveal the silicon device layer that is used as the vibrating top electrode for the CMUT sensors. Metallization stacks on the Silicon device layer have been deposited for electrical conductivity enhancement and wire bonding connections between CMUT top electrodes and printed circuit boards (PCBs). After the patterning of the vibrating top electrode layer, dicing saw processing is done to singulate the CMUT chips from 4-inch diameter wafers. Chip-scale sealing of the CMUT chips is done by conformal Parylene C deposition using UV-sensitive dicing tape as a manual mask to prevent the deposition of Paylene C on the electrical pad regions of the CMUT chips. After Parylene C deposition, UV-sensitive dicing tape is removed from chips to reveal the electrical connection pads. CMUT array devices are characterized by inspecting their capacitive gap height, measuring their resonance frequencies, and determining the integration process yield. The resonance frequency results obtained from impedance analyzer measurements of individual CMUT cells are around 5.7 MHz. Furthermore, change in the resonance frequency is clearly detectable when the applied DC bias voltage is increased during the small AC plus incremental DC excitation of CMUT cell membranes. Keywords: Microelectromechanical Systems (MEMS), Capacitive Micromachined Ultrasound Transducer (CMUT), Microfabrication, Wafer-scale Batch-Compatible Microfabrication, Dicing Saw, Fully Automated Dicing Saw Processing, Anodic Wafer Bonding, Photoacoustic Imaging (PAI).
Cam elyafların gelişmiş mekanik ve kimyasal özellikleri için metal oksit nanopartikül kaplamalar
Glass fibers are one of the most used reinforcement fibers in composites. They have highly demanded properties such as high mechanical properties, impact resistance, high strength-to-weight ratio, and cost-efficiency. Glass fiber composites are utilized in many fields such as aerospace, automotive, and maritime. Glass fibers are one of the components in the composite structure aside from the resin matrix and their properties heavily affect the overall properties of the composite material. Improving the properties of glass fiber reinforcement, the composite performance can also be improved. Industrial-scale fabrication of glass fiber requires the construction of a certain glass-type exclusive factory. This study aims to have an alternative solution to meet the strength demands of industry with a relatively simple modification to the production process of E-glass fibers. In this study, the mechanical, chemical, and dielectric properties of glass fibers are altered via metal oxide nanoparticle doping. A thin layer of ZnO coating is applied onto the E-glass fibers via the dip coating method. Through spectroscopic and SEM characterization, the presence of ZnO coating is confirmed and the effect of this coating on mechanical properties is investigated through micromechanical analysis. ZnO coating proved to increase the tensile strength of E-glass fibers by 15.65%. In addition to mechanical improvements, the ZnO nanoparticles proved to be effective in corrosion resistance. Their corrosion-resistant properties are investigated using an acidic environment. Coated fibers are then used to manufacture a glass fiber felt composite to investigate the effect of nanoparticles on signal transmittance properties of glass fiber composites. In addition to modification of common E-glass fibers, a novel pure silica fiber fabrication method for advanced aerospace composite application is developed. Principles of optical fiber production is utilized to fabricate structural high purity fiber with unconventional fuel gas heating source. This study aims to obtain know-how knowledge on the production of pure silica fiber. To fabricate the pure silica fiber, a novel custom fabrication setup is designed and manufactured. This setup includes a custom heating system, custom capstan tractor, and a custom feeding system.
In vıtro fare ve ın vıvo zebrafısh modelleri ile farklı diyetlerin anjiyogeneze etkisi
Cardiovascular disorders rank as the primary cause of global mortality. Being overweight or obese impacts the pathogenesis of cardiovascular disease, resulting in an imbalance in endothelial function, cell growth, and inflammatory activation (Shrestha et al. 2020). Disruption of these factors resulting from endothelial cell dysfunction serves as both an outcome and a catalyst for vascular disease processes. Endothelial cells (ECs) are a natural barrier between circulating blood and vessel components. They also play critical roles in multiple physiological and pathophysiological processes, such as angiogenesis, vascular permeability, and inflammation. Amelioration of endothelial dysfunction may be attained by weight loss; however, complementary in vitro and in vivo studies are needed to establish the effects of weight loss on endothelial function and angiogenesis. This study developed an in vitro model to understand better the diet-induced changes in angiogenesis for mouse endothelial cells. In addition, a novel in vivo model of diet-induced vascular dysfunction and its reversal with a regular diet in a zebrafish model was also studied. In this study, in vitro studies show that a high-fat diet (HFD) has a proliferative effect on endothelial cells and weight loss does not compensate for prior stress induced by HFD. In vivo studies showed that an egg yolk-based high-fat diet might affect hepatic and angiogenesis parameters, on which weight loss partially affects both larvae and adult zebrafish. These preclinical models can be helpful experimental models to study diet-induced changes in angiogenesis and regeneration under different dietary regimes.
Ws2'nin 1h, 1t ve 1t' fazları için optimize edilmiş stıllınger-weber potansiyelleri: termal taşıma örneği
The advent of graphene has poured numerous amount of research effort into the study 2D materials and utilizing it for device fabrication. Monolayer Transi- tion Metal Dichalcogenides are one such class of polymorphic material with high prospect in versatile device applications due to its unique properties exhibited across the various phases. Classical Molecular Dynamics is a powerful tool that can be utilized to study the thermal and mechanical properties of these phases. Considering this, we optimise Stillinger-Weber type Potential for the seperate 1H, 1T and 1T′ phases of WS2 using Particle Swarm Optimization. These potentials are validated by comparison of phonon dispersion curves, Density Functional The- ory (DFT) based target characteristic data and through an accuracy assessment conducted using Non-Equilibrium Molecular Dynamic (NEMD) simulations to evaluate thermal conductivity of the polymorphic structures. Thermal conduc- tivity results obtained for 1H and 1T′ are in good agreement with first principle predictions calculated using Boltzmann Transport Equation. NEMD simulation of 1T phase prove to be challenging due to its dynamic instability with incoherent buckle structure formation along the symmetric directions.
Glioblastom senesensinde alcam rolünün incelenmesi
Glioblastoma is a type of glioma that is the most common brain tumor in the Central Nervous System (CNS). Based on this classification, it is the highest-grade astrocytoma (grade IV), highly aggressive and invasive brain cancer. The primary treatment for GBM involves surgical resection to remove as much of the tumor as possible. This is typically followed by radiotherapy and concurrent temozolomide (TMZ) chemotherapy. Despite these multimodal approaches, the prognosis for GBM patients remains poor, with a median survival of approximately 12-16 months. It is already known that the high invasiveness causes the cancer to reach other tissues in the body. If the cells could migrate to other regions but couldn't proliferate, this would increase the lifespan following the diagnosis. Therefore, one of the most important reasons why these treatments are not effective is the fact that cells can escape senescence induced by TMZ. New genetic tools or targets are needed to help to keep the cells in senescence state or to induce senescence more effectively. Here, in this study, we wanted to investigate the role of Activated Cell Adhesion Molecule (ALCAM) in glioblastoma senescence. In the literature, it has been shown that glioblastoma patient survival decreases with the increased ALCAM level. Moreover, in patient-derived xenografts, cells with overexpressed soluble ALCAM showed more aggressiveness. On the contrary, when ALCAM was decreased in glioblastoma cell lines, the colony formation ability increased. Therefore, the role of ALCAM in senescence and especially in glioblastoma senescence, if there is, has remained elusive. To shed light on this unclarified relationship, we used ALCAM targeting siRNA and constructed plasmid overexpressing it to manipulate the ALCAM gene level in glioblastoma cells. Expression levels of senescence markers and SA-βgal staining percentage were investigated upon these manipulations. Although significant changes were observed in senescence markers, we cannot say they were consistent or relatable. There is a need for a more comprehensive study to understand the correct relationship. Moreover, conditions like tumor microenvironment, stem cell subpopulation percentage and combinatorial effects should be considered.
Biyohareket algılama ve sağlık uygulamaları için düşük boyutlu malzemeler entegre triboelektrik fiberlerin termal çizimi
The potential of flexible wearable devices and sensors to revolutionize healthcare lies in their ability to facilitate real-time monitoring. However, many of these wearable sensors are extensive energy consumers, and the requirement of bulky energy storage devices significantly hampers their acceptability. Currently available sensing devices mostly employ film-based devices, which lack breathability, reducing their applicability in widespread healthcare applications. Triboelectric nanogenerators (TENGs) are environmentally sustainable devices that convert mechanical and biomechanical energy into electrical output through the synergistic processes of triboelectrification and electrostatic induction. These devices effectively harvest low-frequency mechanical and biomechanical energy and enable self-powered sensing. TENG performance can be enhanced by incorporating low dimensional materials with high specific surface areas into flexible ferroelectric polymers. Ferroelectric polyvinylidene fluoride (PVDF) and its copolymers are particularly advantageous due to their high dielectric constant and abundance of highly electronegative fluorine ions. Various low dimensional materials can interact with the polar groups of PVDF and reorient them to conform to electroactive phases. Moreover, they can also form micro-capacitors and modulate the surface properties of nanocomposite. In this thesis, we aim to address the issue by preparing a triboelectric nanogenerator integrated textile fiber with self-energy generating ability and breathability as textiles. We employed the thermal drawing process as a fabrication platform for preparing continuous triboelectric fibers. Graphene nanoplatelet (GNP) and Molybdenum disulfide (MoS2) are added to the PVDF matrix to improve triboelectric properties. β phases of thermally drawn nanocomposite fibers demonstrate significant improvement and were increased to 37.6%, 39.5%, and 43.3% for 1, 3, 5% GNP integration. For the case of MoS2, β phase increases to 47.5% for 3 wt% MoS2; however, β phase decreases beyond 3 wt%. The nanocomposite TENG fibers demonstrate improved triboelectric properties. The fibers show superior sensitivity, flexibility and durability, enabling their applications in critical healthcare applications.
Kırım-Kongo kanamalı ateşine (KKKA) karşı tedavi stratejilerinin geliştirilmesi
Crimean-Congo Hemorrhagic Fever (CCHF) is a highly fatal and zoonotic arboviral infection in humans. It is caused by the CCHF virus, which precipitates severe hemorrhagic outbreaks with a mortality rate reaching up to 40%. CCHF is classified as an arboviral disease due to its transmission through tick vectors of the Hyalomma species, which are arthropods. Human infection occurs either via bites from infected ticks or through exposure to the bodily fluids of infected animals or patients. Since the initial reported case in Turkey in 2002, a total of 9,700 cases have been documented. The disease is endemic in Turkey, positioning it as one of the most affected countries by CCHF within the European region. Currently, there is no effective protective measure, such as a vaccine or specific antiviral treatment, for CCHF. This lack of effective countermeasures constitutes a significant public health threat and a serious sociological issue. The aim of this study is to develop virus-specific and host-safe strategies against CCHF to directly inhibit virus infection and/or subsequent treatment of the disease. For this purpose, the CRISPR/Cas13b genome editing tool will be utilized. RNA editing systems, such as CRISPR-Cas13b, offer the advantage of controlling gene expression without altering the underlying DNA sequence and can exert transient modifications at the RNA level, making them promising tools in combating RNA viruses. The two virus genome segments, the S segment, which encodes the nucleocapsid protein to protect and organize the viral genome, and the L segment, which encodes RNA polymerase for replication and transcription processes necessary for viral propagation, will be rendered ineffective using the CRISPR/Cas tool. Finally, to demonstrate the inhibition of CCHFV replication in HEK293 cells via the CRISPR/Cas13b system, recombinant adeno-associated virus (rAAV) will be used as the gene delivery agent. If the proposed hypothesis is confirmed, the project will significantly impact the country with the know-how generated.
Temas ve gerilim geri bildirimine sahip elastik baskılanmış elektronik devreler
Bu teknolojik devrim çağı, günlük insan yaşamında kullanılan elektronik ve ci hazlarım daha kişisel ve interaktif hale getirilmesinde daha fazla yenilik gerek tirmektedir. Esnek ve çok fonksiyonlu sensörlerin geliştirilmesine olan büyük ilgi ve arastirmalar, bu talebin bir sonucudur. Ancak, bu tür esnek giyilebilir ciha zları, kitlesel üretimde kullanılabilecek veya yüksek kaliteli laboratuvar teknolojisi gerektiren ek karmaşik adımlar gerektirmeyen basit ve maliyet etkin yaklaşimlar kullanarak üretmek hålá önemli bir xorluktar. Bu te, stencil baski gabi hal basit ve maliyet etkin bir teknoloji kullanarak kitlesel üretime uygun esnek ve giyilebilir sensörlerin geliştirilmesi ihtiyacnı ele almaktadır. u çalişmada, karbon siyahi parçacıklarımın grafen tabakaları arasında dolgu malzemesi olarak davranmasımı kullanarak mürekkebin elektriksel performansin arturan, grafen/karbon siyahı kompleksi bazlı bir iletken mürekkep geliştirilmistir. Polikarbonat kullamlarak yapilan polimer desdekli baglama işlemi, mürekkebin istenilen desenlerle kolayca basılabilmesini ve mükemmel yapişma ve stabilite sağlamasinı mümkün kılmıştır. Ilk olarak, farklı basınç seviyelerini algilayabilen fonksiyonel bir dövme geliştirilmiştir. Bu dövme, basınç degişimi ile iki boyutlu bir kapasitörün kapasitansındaki değişimi kullanarak çalişır. Kapasitif sensörün performansinı artıran, elektrotlar arasındaki etkileşim alanını artıran interdigi tated tarak geometrisi kullanılmistır. Kapasitif dokunmatik sensör, farkli basinç seviyelerini farkli zaman aralıklarında hizli ve tutarli performansla ayırt ede bilmistir. Avnica, pamuklu kumas althk üzerinde avm stencil baski mctodolojisi kullanılarak insan hareketi ve bükülmeyi algılayabilen esnek bir tekstil tabanlı gerinim sensörü geliştirilmiştir. Sensör, farklı bükülme seviyelerini tespit ede bilmiş ve ayrica hızli ve yavaş bükülme hareketleri arasında ayrim yapabilmiştir. ast, tekstil tabanli gerinim sensörü birden fazla yikama döngiistine dayan abilmiş ve gerinim algılama için benzer performans eğilimleri sergileyebilmiştir.
Doku mühendisligi ve çip-üstü-organ uygulamalari için hibrit GelMA tabanli mikrojellerin dinamik ortamlardaki iskelet özelliklerinin incelenmesi
Microgels have emerged as versatile materials in tissue engineering, drug delivery, and organ-on-chip (OoC) platforms due to their small scale, uniformity, and customizable properties. Their adaptability as injectable materials and dynamic scaffolds makes them promising candidates for a wide range of biomedical applications. However, traditional methods for characterizing their physical and mechanical behaviors, designed for bulk hydrogels, do not capture the unique properties of microgels, which differ significantly in terms of size and surface-to-volume ratio. This work explores the physical properties of Gelatin Methacryloyl (GelMA)-based Collagen and Hyaluronic Acid Methacrylate (HAMA) hybrid microgels produced via droplet microfluidics, employing novel assays tailored specifically to their micro-scale. Real-time observation of their swelling and degradation properties is carried out using a custom-made platform enabling the tracking of individual microgels, and electron microscopy provides insights into their internal structures, revealing previously unobserved behaviors. We have shown the interpenetrating network formation when GelMA and Collagen are used; and copolymer formation when GelMA and HAMA are used. Under the effect of Collagenase and Hyaluronidase, the individual microgels showed different degradation mechanisms, which have proven to be affected by crosslink densities, enzyme-substrate specificity, enzyme saturation, and properties of the individual network components. The work is extended by focusing more on the temporal profiling of GelMA and HAMA hybrid microgels' behaviors under enzymatic degradation, examining how volume, mechanical properties, and surface features evolve over time, simulating the dynamic conditions encountered in vivo during especially tissue engineering applications. We found that instead of carrying out separate assays to understand the changes, a more holistic approach to evaluating the aforementioned properties gives a more thorough discussion. This approach revealed that changing the ratios of GelMA against HAMA affects the crosslink densities, network formation, and ultimately degrative behaviors. We have observed, for the first time in droplet microfluidics, that a certain combination of GelMA HAMA results in microgels with a network gradient, getting denser towards the center, while the other combinations only increased the crosslink densities without altering the porous homogeneity. Furthermore, the number of microgels exposed to the same concentration of enzyme is altered to emulate different injection volumes into similar tissues, or the enzyme concentration is altered to emulate injection into different tissues. These assays showed the sensitivity of degradation profiles against enzyme saturation and competition. Meanwhile, the stiffness and surface morphology changes of microgels during degradation are examined, revealing the importance of network homogeneity in presenting stable mechanical properties during degradation. Lastly, drug release from these scaffolds is modeled for prospective applications, and their relation to scaffold properties is evaluated. Overall, this thesis is poised to discover the peculiar behaviors of GelMA hybrid microgels produced with droplet microfluidics uncovering the importance of carrying out investigations true to the sample at hand and the conditions that will be imposed upon them during application.
Biyogörüntüleme ve biyosensing için genetik olarak tasarlanmış mikroplar
The advantageous approach to the utilization of the microbes for bioimaging and biosensing underlies under their active motility and self-propulsion characteristics besides their easy bioengineering feature to gain multi-functional activities. The emerging developments make use of microorganisms as therapeutic agents in disease diagnosis and treatment. The dynamic nature of the habitat forces the microorganisms to acclimate themselves to changing living conditions via evolving exclusive bio-functionalities for their survival. Therefore, the living microorganisms producing functional materials serve as a biohybrid system with unprecedented potential for enhancing the detection of a disease biomarker molecule or meeting the great need in cancer diagnosis. The synthetic biology approach, a multidisciplinary field of science, gives the ability to engineer and modulate the microorganisms to redesign existing natural pathways, resulting in the gain of the desired function. Inspiring form nature, the biomineralization of iron-oxide materials is demanding for their potential usage in antitumor effect due to their easy modulation, stability, and magnetic properties. Furthermore, the certain respiratory capacities of electrochemically active microbes enable the respiration of diverse inorganic and organic molecules for their survival in redox-stratified environments. The ability of exchanging electrons with electrodes possesses several diverse biotechnological applications like the construction of microbial fuel cells, electro-fermentation, and electro-genetics. In this thesis, the microbes were engineered for their utilization in bioimaging and biosensing applications. Firstly, intracellular and extracellular magnetite accumulating Escherichia coli bacterial cell machineries were constructed as contrast agents for the MRI scanning, promising for a cancer diagnostic. Secondly, the intracellular magnetite accumulating bacterial cells, possessing all the redox reactions that readily take place in their cytoplasm via synthetically produced proteins, were further engineered to improve their targeting capability for breast cancer tumor cells by displaying a certain nanobody on the cell surface. Thirdly, electronic sentinel bacterial cells were designed utilizing the electron transfer modules for extracellular electron consumption by targeted acceptors for their wireless biomonitoring applications upon detecting a disease molecule. The methodologies described in this thesis are envisioned as promising tools for diagnostic applications.
Genetiği değiştirilmiş mikroorganizma kullanarak plastik degradasyonu
The usage of PET plastics in daily life have excessively increased in the last decade. The increased usage of PET is accompanied with the massive amount of PET waste accumulating rapidly. Environmental pollution caused by this waste has reached a critical point with pollutants being found even in the most remote parts of the world. Causing massive damage to ecosystems and even human health, PET plastic waste needs to be handled urgently. Although there are ongoing PET recycling and treatment efforts, the current methods in use are insufficient. The techniques currently used are either costly, leave a significant carbon footprint or are lacking in their ability to recycle microplastics. However, with the discovery of microorganisms which have the ability of degrading PET, biodegradation of PET products has emerged as a promising green alternative. In this thesis we designed bacterial tools to utilize the PET hydrolyzing enzyme, PETase. For this purpose, living bacterial platforms were engineered. The first system employed E. coli as the host to display PETase on the cellular surface. With PETase molecules anchored on its surface, aiding in the stability and the activity of the enzyme, the system will be a useful tool for PET degradation. For the surface display system, the Ag43 autotransporter protein is used. The system was cloned, and expression was analyzed using immunocytochemistry labeling. The activity of the system was analyzed with chromatography and mass spectrometry. The second system proposed uses E. coli once again as a workhorse for PETase secretion, creating a simple yet effective tool for the bioremediation of PET. For secretion of the enzyme, the disruption of Braun's lipoprotein to create a leaky outer membrane is exploited. The system was cloned, and the cloning was verified. Also, the activity of native PETase was analyzed with HPLC and mass spectrometry. With this analysis, the PET degrading activity of PETase was confirmed.
Dağıtık dalga kılavuzu tasarımı ile yüksek güçlü yarıiletken lazerlerde ısıl yükün azaltılması
Semiconductor lasers lead laser technology due to their high efficiency, compact size, and cost-effectiveness. Among these, GaAs-based laser diodes (LDs) are the most efficient light sources, but are still constrained by self-heating, which elevates internal temperatures and degrades performance, output power, and device lifetime. Traditionally, increasing the cavity length has mitigated this issue by improving thermal conductivity, facilitated by advances in epitaxial growth, design, and device packaging. However, the cavity lengths of high-power GaAs LDs are now limited to approximately 5 mm, beyond which the output power declines because of intrinsic physical constraints. This work presents a new type of waveguide design, called distributed waveguide (DWG), that overcomes conventional cavity-length limitations. The DWG integrates lasing and secondary sections along the waveguide, which are electrically isolated to control current injection, yet optically connected for efficient beam transport. The laser section is electrically pumped to generate output, while the secondary section operates near-threshold to dissipate heat effectively. Extending the cavity length from 4 to 8 mm, DWG LDs exhibit significantly improved thermal management with favorable device characteristics. Experimental results, corroborated by numerical analysis, demonstrate that DWGs achieve approximately 1.8× lower junction temperature change while delivering high output power. Additionally, the DWG platform and its fabrication process are fully compatible with standard semiconductor laser manufacturing techniques, ensuring industrial adoption. This work provides clear evidence that innovative waveguide designs can effectively mitigate self-heating, promising enhanced performance, output power, and reliability in semiconductor lasers.
Gaas(110) yüzeyi üzerinde geçiş metali dimerler: Bir yoğunluk fonksiyoneli (DFT) çalışması
Dilute magnetic semiconductors (DMSs) have gained appreciable interest in the past two decades. This is due to the perspectives of both fundamental physics and novel applications. They are useful in the context of single dopants (solotronics) because studying individual dopants and their interactions with the host provides rich physics. Here we carry out density functional theory calculations for transition metal element dimer dopants on GaAs (110) surface using Quantum Espresso software by employing ultra-soft pseudopotentials (USPP) and report properties such as exchange energy, spin-resolved density of states, spin-resolved projected density of states, structural and magnetic relaxations, and STM images of surface with dimers. We model the GaAs (110) surface with the BURAI software package, and we study 4 transition metal dimers on near and far configurations on the surface, Fe, Cr, V, and Co. Since the dopants are magnetic, we consider both the ferromagnetic and antiferromagnetic alignments. We show that magnetic configurations greatly alter the relaxed positions of dopants. We also report the exchange energy between ferromagnetic (triplet) and antiferromagnetic (singlet) states for near and far configurations. At the end of our calculations, we found the relationship between exchange energy and distance and reported a dramatic change in the magnitude of the exchange energy as a function of dimer separation. We also observe that except for the Co dimers, Fe, Cr, and V dimers have a reasonable exchange energy between ferromagnetic and antiferromagnetic alignments. This is due to nonzero magnetic moments on these transition metal dopants. For less than two percent of dopant ratio, we observed a metallic system for Fe dimer, a semiconducting system for Cr, and a half-metallic system for V dimers. Electronic structure calculations such as DOS and PDOS projections are in parallel with the expectations of ferromagnetic and antiferromagnetic alignments. We also study scanning tunneling microscopic images of these dimers on the surface showing a large contrast under a bias voltage of 1V. Semiconducting surfaces such as GaAs hosting transition metal dopants with d-orbitals in this thesis have the potential to be excellent platforms for novel quantum applications such as fast-switching qubits. Also, reported spin-resolved density of states (DOS) and spin-resolved projected density of states can be used to understand the hybridization of bands, exchange splitting on orbitals, and design materials for future spintronic and optical applications.
Havacılık metamalzemeleri ve fonksiyonel kaplamalar
Optically transparent and electrically conductive thin-film coatings are widely used to functionalize surfaces of various high-technology platforms, including mobile phones, displays, detectors, and LEDs. Their integration into aviation transparencies, such as canopies, windshields, and windows, is widely known and used for de-icing purposes. However, there are limited reports or information available about using such thin-film coatings for electromagnetic interference (EMI) shielding, low observability (LO), and solar irradiation protection features. This thesis aims to study and demonstrate optically transparent aviation structures possessing the properties of EMI shielding, LO features, and solar radiation protection altogether. To this end, in this thesis, we specifically addressed the problem of achieving high EMI shielding and solar protection, which require high electrical conductivity, resulting in a trade-off reducing the optical quality and LO performance. Transparent engineering polymers are widely used in structural parts in aviation thanks to their enhanced mechanical performance. However, good-quality films require high-temperature processes, which is not applicable to transparent aviation structures. Therefore, the architecture of layered films can be applied to meet the requirements of well-featured aviation transparencies. For these purposes, in the thesis we also designed monolithic and laminated aviation transparencies with surface modification based on stratified films and their patterned ones using numerical and experimental methods. We developed numerical approaches for the design of aircraft transparencies, including both the optical and electromagnetic requirements and validated our results. We successfully conducted experimental studies for uniform large-area thin-film coatings onto aviation transparencies. The results revealed that EMI shielding and solar control performance were achieved with minimal optical losses for planar structures. LO requirement was incorporated into prototypes built on curved or laminated transparent structures instead of monolithic ones to sustain optical, solar protection, and EMI shielding performance to a possible extent. We showed that the low observability performance of such patterned structures, the metamaterials, is enhanced in terms of bandwidth and attenuation compared to the planar thin-film-coated monolithic counterparts. These multi-functional thin-film coatings are essential in aviation, especially for high-performance 5th-generation fighter jets and other civil applications. This thesis paves the way for thin-film-coated transparent aviation structure designs across different domains, including visible, infrared, and microwaves, to enable their multi-functionality at large scales. The experimental large-area coating method guides the coating of a large and complex area to remove the limitation of metamaterial applications at the industrial level. We believe that our findings in this thesis will help to replace traditional planar thin film coatings with metamaterials at the industry scale, aiming to outperform traditional counterparts.
Hücre dışı veziküllerin gerçek zamanlı olarak yakalanması ve salınması için ısıya cevaplı polimer entegre metayüzey sensör
Extracellular vesicles (EVs) play pivotal tasks in intracellular communication, carrying biomolecules such as proteins, lipids, and nucleic acids that reflect the physiological state of their originating cells. Isolating EVs purely from complex and protein-rich matrixes is crucial for understanding cellular processes and disease progression. The gold standard method for isolating EVs is ultracentrifugation, yet it has severe obstacles in terms of requiring expensive equipment, non-vesicular impurities, and possible damage on the EV surface. Owing to these drawbacks, their further analyses, isolation and detection through their surface markers are challenging. This study aims to integrate a smart thermoresponsive polymer with a metasurface plasmonic sensor, which is further decorated with anti-CD63 antibodies to capture EVs derived from MCF-7 breast cancer cells as a model system. We later isolate (release) these EVs by simply altering the local temperature above the lower critical temperature (LCST) of the polymer. Basically, the thermoresponsive polymer exhibits hydrophilic characteristics below its LCST and becomes hydrophobic when the temperature is increased above the LCST. The optic plasmonic sensor has a well-defined nanoperiodic array, presenting surface plasmons while exciting the surface with a normal angle of incident light. Therefore, the metamaterial sensor denotes real-time and label-free detection of EV binding and release events. This enables the quantitative analysis of EVs. In a nutshell, leveraging the distinctive thermoresponsive characteristics of the polymer, we presented a novel methodology designed to selectively immobilize EVs through antibody interactions and subsequently release them by elevating the temperature. This process enables the isolation of EVs with a high degree of purity, free from non-specific molecular contaminants. Consequently, our pioneering approach opens a promising new way for studying EVs and their surface markers in great detail, unrestricted by the limitations of conventional separation techniques, and contributes to the understanding of complex cellular processes and the subtle development of illnesses.
Grup III monokalkojenür nanoşeritlerin yapısal, elektronik ve manyetik özellikleri
Owing to the promising optoelectronic and thermoelectric properties of two-dimensional (2D) group III–VI materials (MXs), their nanoribbons (NRs) have attracted notable attention as an emerging class of quasi-one-dimensional (quasi-1D) nanostructures. Due to the fact that the most stable 2D monolayer polymorph of MXs is the 1H phase, to date, existing studies in the literature have predominantly focused on the NRs formed from 1H phase MXs. Nevertheless, NRs of the 1T phase have received little to no attention. Employing ab initio simulations based on density functional theory, we systematically compared the thermodynamic stability of hydrogen-passivated and unpassivated 1T and 1H zigzag (ZNR) and armchair (ANR) edge NRs of GaS, GaSe, and InSe. Our results reveal that nonpolar 1T phase MX ZNRs are thermodynamically more favorable than polar 1H MX ZNRs at widths up to 34 nm, a range that is realizable through contemporary experimental fabrication techniques. On the other hand, as both 1H and 1T ANRs are nonpolar, 1T is more favorable only in unpassivated cases in very narrow widths of up to 3.3nm in the case of InSe ANRs. Furthermore, unlike metallic 1H ZNRs, 1T ZNRs remain semiconductors and retain Mexican-hat-shaped (MHS) top valence bands. Complementarily, hydrogenation energies of 1T InSe NRs are positive, and due to the edge-localized states, the 1T unpassivated ZNRs possess nearly flat top valence bands. These electronic properties present compelling opportunities for exploiting 1T MX NRs in spintronic applications. We demonstrate that, upon hole doping, these MX NRs develop itinerant magnetization across a broad range of carrier densities and display half-metallic behavior, with only one spin channel intersecting the Fermi level. Moreover, the spin-polarization energies (SPE) of these NRs increase remarkably relative to their 2D counterparts, indicating stronger stability of the ferromagnetic state. We elucidate that the SPE of NRs strongly depends on the degree of edge-localization of the carriers along the width of NRs, which in turn depends on the edge passivation, width, and edge shape of NRs. Overall, this study highlights the critical interplay between the thermodynamic favorability of the novel 1T phase MX NRs below certain critical widths and the resulting electronic and magnetic properties, which together enable their promising applications in spintronics and nanoelectronics.
Simplex kodlanmış OTDR-tabanlı dağıtık sıcaklık algılama
Temperature sensing for environmental and structural monitoring is of utmost importance for certain applications, e.g., monitoring of wildfires, gas pipelines, electric lines, temperature of facilities such as nuclear reactors, etc. Conventional devices to measure temperature along many kilometers are not cost-effective, and are impractical to install each measurement device. The solution heralded was to utilize the back-scattered Raman signal inside the optical fiber to measure the temperature, as the Raman scattering is a manifestation of the interaction of light with molecular vibrations (optical phonons). Each scattering point along the fiber serves as an individual sensing element, and for that reason, this technology is called 'Distributed Temperature Sensing' (DTS). However, the problem with Raman OTDR-based DTS originates due to the Raman signal being weak as much as 70dB below the launched optical power, resulting in a low signal-to-noise ratio (SNR). Increasing optical power is not viable because of optical nonlinearities. To overcome this problem, advanced noise filtering techniques and interrogation methods can be used. An interrogation method named Simplex coding is widely used in the literature, which involves the modulation of the amplitude of the laser, based on a predetermined code word. In this way, more than one pulse can be present during each interrogation, which then suppresses the uncorrelated additive white Gaussian noise. Optimizing the SNR enables longer sensing distances and higher temperature resolution performance in Raman OTDR-based DTS systems. In this thesis, first, a commonly used Wavelet-transformation-based denoising is experimentally demonstrated in a multi-mode fiber equipped RDTS system. The method has improved the temperature resolution from 0.45◦C to 0.10◦C at 5.5km. Finally, 7-bit Simplex coding is experimentally demonstrated in a single-mode fiber equipped RDTS system. The Simplex coding method has improved the temperature resolution from 1.3 ◦C to 0.8 ◦C at 5km.
Sağlikli ve hastalikli durumlarda nükleer laminanin yapisal ve dinamik özelliklerinin polimer temelli modellemesi
The nuclear lamina, composed of fibrous lamin proteins, forms a two-dimensional protein meshwork that preserves the structural integrity, elasticity, and morphology of the nucleus. These lamins—A/C-type and B-type—assemble into dynamic, mechanically responsive networks, much like semiflexible chains in polymer physics. In healthy nuclei, this network behaves as a random, isotropic meshwork, that can be disrupted in several diseases. An example is Progeria (HGPS), where a single point mutation in the LMNA gene (A-type lamins) results in a reduced exchange between peripheral lamins and nucleoplasmic ones. Mutated lamin A proteins (progerin) assemble into closely packed nematic phases at the nuclear periphery. These changes alter the B-type lamin network as well—enlarging mesh faces and disrupting overall organization—alongside affecting the mechanical properties and morphology of the nucleus. In other words, the structural properties of the lamina in health and disease affect 3D chromatin architecture and regulate the nucleus's ability to withstand mechanical stress. Despite these biological insights, the polymer physical mechanisms that govern lamin network formation, phase behavior, and mechanical response are largely unexplored. To address this, we present a coarse-grained molecular dynamics (MD) model that treats lamin filaments as rod-like polymers confined within the nucleus. Our model can recapitulate the lamina's nematic phase formation in disease with increasing lamin concentration in rigid nuclear confinement. Furthermore, at low inter-lamin attraction, lamins kinetically dissociate from the periphery, reminiscent of healthy nuclei. Under elastic nuclear confinement, surface adsorption of rod-like polymers alone is sufficient to control the shape of the elastic shell. This illustrates how polymer-surface interactions alone can independently influence nuclear morphology, irrespective of chromatin phase behavior. Furthermore, our results suggest that lamin adsorption to the elastic nucleus can affect the mechanical response in the short extension regime, acting as a determinant of nuclear stiffness in our model. This is unexpected, as experiments of isolated nuclei often attribute short-extension mechanics primarily to chromatin. We also find that the interplay of lamin intermolecular interactions yields diverse lamina topologies—from isotropic meshes to paracrystalline arrays— with varying face size, shape, and connectivity. Extending the model to include chromatin as a phase-separating polymeric component reveals a cooperative mechanism: self-assembled lamina can peripherally localize heterochromatin, establishing conventional nuclear architecture. Importantly, we find that lamin localization needs to precede lamin-heterochromatin attraction to encourage proper chromatin compartmentalization. Otherwise, chromatin fails to compartmentalize properly, and lamin fibers accumulate in the nuclear interior—disrupting both lamin and chromatin organization. Moreover, our analyses show that lamin-chromatin interactions are essential to generate a distinct mechanical response from the lamina when applying mechanical stress to the nucleus. This highlights the cooperative role of chromatin in lamina-mediated nuclear deformation. Introducing a meshless membrane to represent the nuclear envelope further captures dynamic nuclear deformations such as bleb formation and nuclear elongation, driven by distinct polymer-like behavior lamin fibers and chromatin networks. Together, this work frames nuclear lamina dysfunction in disease from a polymer physics perspective. Our results connect altered molecular interactions and lamina assembly to morphological and mechanical alterations of the eukaryotic nucleus in disease. It offers molecular dynamics framework to understand how altered lamin stoichiometry and phase behavior drive nuclear abnormalities in health and disease.
Sentetik biyoloji yaklaşımı ile anti-diyabetik yaşayan ilaç geliştirimi
Type 2 Diabetes Mellitus (T2DM) is a prevalent metabolic disorder characterized by insulin resistance and impaired glucose regulation. Peptide-based drugs such as GLP-1 and its analog Exendin-4 are widely used in clinical treatment due to their ability to enhance insulin secretion and improve glycemic control. However, frequent injections, enzymatic degradation in the gastrointestinal tract, and short half-life limit their therapeutic efficiency and patient compliance. To address these challenges, this study aims to develop a living therapeutic system that enables the dynamic, gut-responsive production of anti-diabetic peptides using engineered Escherichia coli Nissle 1917. In the first part of the study, whole-cell biosensors responsive to physiologically relevant stimuli such as fatty acids, bile salts, and aspirin were constructed using synthetic regulatory elements. These biosensors were initially characterized through the expression of a fluorescent reporter gene (sfGFP) to determine their dose-response behavior and functionality. Following successful characterization, the reporter gene was replaced with either GLP-1 or Exendin-4 coding sequences, fused to various signal peptides (PhoA, MalE, TorA, DsbA, PelB) to promote extracellular secretion. Gibson Assembly and classical cloning techniques were used throughout the construct designs. The functional activity of secreted peptides was evaluated through ELISA-based quantification and in vitro bioassays using MIN6 insulin-secreting cells. MTT assays were performed to assess cell viability, and glucose-stimulated insulin secretion assays were conducted to determine the biological activity of the secreted peptides. Among the tested constructs, signal peptide–fused versions of GLP-1 and Exendin-4 showed significant effects on cell viability and insulin secretion, indicating successful expression and functionality of the therapeutic peptides. This study demonstrates the feasibility of combining probiotic bacteria with metabolite-responsive gene circuits for targeted peptide delivery. The developed platform presents a promising strategy for designing next-generation living drugs capable of responding to the host environment and offering a self-regulated treatment for metabolic diseases like T2DM.
Nano-gözenekli zeolit a'nin ultrahizli lazer ile sentezi
Zeolites are microporous aluminosilicate self-assembled nanocrystals. Zeolite A is the first commercially synthesized zeolite, which has cubic unit cell that consist of alumina and silica tetrahedra together with the extra-framework cations like Na^+, K^+, Ca^2+. Zeolite A has been widely studied zeolite in the literature owing to the properties like high porosity, high surface area (~600 m^2/g), and high chemical and thermal stability, and high ion exchange capacity. All of these properties make Zeolite A used in various industrial applications like CO_2 adsorption, wastewater treatments, biosensor applications, etc. Although zeolites have a wide range of industrial uses, they have still been extensively investigated in academia as well. Accordingly, various zeolite synthesis methods have been developed, but all have limitations. While conventional hydrothermal synthesis offers benefits such as high-quality discrete crystals, ease of use, safety, and industrial scalability, it lacks precise control over nucleation and growth. A method that combines these advantages with the ability to produce defect-free crystals using low-energy photons within a short reaction time has not been developed yet. To address this, we introduce a new method for synthesizing zeolites (TPA-silicalite-1, zeolite Y, zeolite A, and hierarchical ZSM-5) using ultrafast laser energy deposition. In this approach, energy is deposited on a timescale comparable to the polymerization reactions that drive crystal formation. In this thesis study, we further investigate the ultrafast laser pulses on the synthesis mechanism and crystalline structure of nanoporous zeolite A. Utilizing a femtosecond laser at 1040 nm wavelength, we achieved controlled energy deposition in the precursor suspension, accelerating the reaction via multiphoton absorption and laser-induced flows for nearly uniform-sized zeolite A crystals (~260 nm). Through the controlled deposition of energy, this method achieves rapid crystallization of Zeolite A with high crystallinity (90-100 %) and a narrower particle size distribution compared to the crystals synthesized via the conventional hydrothermal method. Comprehensive characterizations, including Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDXS), X-Ray Diffraction (XRD), High Resolution Transmission Electron Microscopy (HR-TEM), Selected Area Electron Diffraction (SAED), Thermo-gravimetric Analysis (TGA), Brauener-Emmet-Teller (BET), and Fourier Transformed Infrared (FTIR) Spectroscopy, revealed that the laser-synthesized zeolites exhibit structural integrity and quality comparable to conventionally synthesized counterparts. Moreover, CO_2 adsorption capacity analysis was carried out to evaluate the gas capture performance and practical applicability of Zeolite A synthesized via the ultrafast laser synthesis method. The ultrafast laser synthesis method was successfully repeated over 80 times to enable various characterizations. This novel technique offers a rapid and alternative approach to synthesizing zeolites with precise control over structural and functional properties.
Rekombinant konak platformu olarak lactobacillus plantarum'un mühendisliği
Lactobacillus plantarum is a versatile lactic acid bacterium recognized for its probiotic properties and long-standing use in fermented foods. While traditional microbial chassis such as E. coli or S. cerevisiae have dominated recombinant bioproduction platforms, their limitations in food-grade and probiotic applications necessitate the development of alternative hosts. L. plantarum, with its GRAS status, genetic malleability, and resilience under gastrointestinal conditions, has emerged as a promising next-generation chassis, especially for the biosynthesis of health-related metabolites. The aim of this study is to engineer L. plantarum WCFS1 as a recombinant host platform for the production of functional molecules, with an emphasis on 2′-fucosyllactose (2′-FL), a key human milk oligosaccharide known for its prebiotic and immunomodulatory benefits. To achieve this, advanced synthetic biology tools such as markerless CRISPR/Cas9 editing, auxotrophic selection strategies, and modular expression systems will be employed to introduce and regulate heterologous gene pathways responsible for 2′-FL biosynthesis. The project will also focus on overcoming strain-specific challenges such as transformation efficiency, plasmid stability, and metabolic balancing within the host. If successful, the engineered L. plantarum strain will serve as a live, food-compatible cell factory capable of producing 2′-FL either in fermenters or directly in situ as part of synbiotic formulations. The outcome of this work is expected to contribute to the growing field of probiotic metabolic engineering, offering a scalable, safe, and consumer-friendly platform for functional food innovation.
Zayıf ve güçlü kuplaj rejimlerinde kavite-modifiye floresans
The modulation of fluorescence in optical microcavities provides a powerful route for engineering light–matter interactions, with applications in sensing, lasing, and photonic devices. Fabry–Pérot (FP) cavities, composed of planar metallic mirrors enclosing an active medium, enable controlled tuning of emission dynamics across weak and strong coupling regimes. In the weak coupling regimes, cavities reshape radiative decay rates via the Purcell effect. In contrast, in the strong coupling regime, coherent exciton–photon interactions produce vacuum Rabi splitting and exciton–polariton formation. While strong coupling has been extensively demonstrated using narrow-linewidth dyes, such as rhodamines, the behavior of broadband emitters, like fluorescein, under cavity confinement remains poorly understood. This thesis presents a systematic experimental investigation of fluorescein-doped poly(methyl-methacrylate) (PMMA) thin films embedded in FP microcavities. Two concentrations of fluorescein were used, low (20 µg/mL) and high (60 mg/mL), across multiple film thicknesses defined by spin coating speeds (1000–5000 rpm). The low-concentration series comprised films with the thickness of 486, 349, 291, 253, and 240 nm, while the high-concentration series comprised cavities with the film thickness of 669, 476, 380, 334, and 307 nm. Optical properties were characterized by spectroscopic ellipsometry, UV–Vis spectroscopy, steady-state fluorescence, and angle-resolved reflectance. Transfer matrix method (TMM) simulations, incorporating measured refractive indices and extinction coefficients, validated experimental results. At low dye concentrations, cavity confinement primarily induced significant spectral reshaping without mode splitting, consistent with the weak coupling regime. In contrast, high-concentration samples exhibited clear signatures of strong exciton–photon coupling. Angle-resolved ellipsometry revealed secondary loops in the complex-plane ρ trajectories, while reflectance dispersion maps displayed anticrossing behavior when cavity modes overlapped with the fluorescein excitonic transition near 467 nm. Angle-resolved dispersion was fitted with a three-coupled-oscillator model, yielding vacuum Rabi splittings ranging from 34.8 nm to 48.5 nm, and the dispersion shows back-bending of the cavity mode near 467 nm, consistent with exciton–photon coupling. These results demonstrate that, despite its broad linewidth, fluorescein can achieve strong coupling under optimized conditions of high concentration and tuned cavity thickness. The work provides a quantitative framework for extending cavity–emitter studies to broadband dyes and offers design principles for future cavity-enhanced light sources, lasers, and fluorescence-based sensors.
Mikroakışkan çip-üstü-organ modellerinde hücre tutunması için pdms yüzey fonksiyonelliği
The inherent hydrophobicity of Polydimethylsiloxane (PDMS) poses significant challenges for its use in cell culture applications, particularly in organ-on-chip technology. This study presents a novel, versatile, and biocompatible surface treatment method for polydimethylsiloxane (PDMS), designed to significantly improve its cytocompatibility and shear stability in organ-on-chip applications. Four tailored surface functionalization protocols were systematically explored using 3- (Trimethoxysilyl)propyl methacrylate (TMSPMA), optimized to enhance wettability, surface roughness, and chemical functionality, leading to robust and sustained cell adhesion. The efficacy of these treatments was confirmed via comprehensive surface characterizations of contact angle measurements, scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). The changed hydrophilicity supported robust cell adhesion, proliferation and viability that were determined using three distinct human cell types: HUVECs, MCF-7, and Humanderived induced pluripotent stem cells (iPSCs). Importantly, our findings show that the treated PDMS supports long-term adhesion and proliferation under both static and dynamic microfluidic conditions, with minimal cell detachment even under flow rates corresponding to physiological shear stress (~1.5 dyne/cm²). Numerical simulations further validate the experimental flow conditions, strengthening the model's physiological relevance. This study underscores the effectiveness of TMSPMA treatment in improving PDMS compatibility for cell culture, offering an accessible, tunable, and scalable solution for researchers aiming to create more reliable and biologically relevant microfluidic systems.
Lityum klorür ve dairesel RNA delesyonlarının caenorhabditis elegans yaşam ömrüne etkisinin araştırılması
Aging is defined as the defects that occur over time in the tissues and cells of the organism. These defects constitute the primary risk for neurodegenerative and cardiovascular diseases, cancer, diabetes, and many other diseases. Even though some common hallmarks are defined in aging organisms such as genomic instability, loss of proteostasis, cellular senescence and more, the reason behind aging is not completely understood. The aging field, therefore, research how and why do organisms age, and tries to delay or possibly revert this process. This is mostly done on model organisms, and the roundworm Caenorhabditis elegans (C. elegans) is one of the best models for aging research due to its short life cycle. In the first part of this study, the correlation between aging and lithium chloride treatment was aimed to be understood. This substance is commonly used as a drug in bipolar disorder, and an extension of lifespan upon lithium chloride treatment has been explored in multiple studies on different models. A pathway analysis was performed to determine what could be an unknown regulator of this process, and the worm ortholog of the human protein Rev-erb-α, NHR-85, was identified as a possible contributor. A loss-of-function mutation of this protein was found to extend lifespan in C. elegans when compared to its wild type, and lifespan was further extended by treatment with lithium chloride. A decay in brood size and locomotion functions was also observed upon treatment, but it is suggested that this may contribute to the extension of lifespan. Furthermore, it is suggested that this extension in lifespan could be caused by a developmental delay. In the second part of this study, it was aimed to understand whether some age-accumulated circular RNAs of C. elegans could be contributing to the aging process. Circular RNAs are covalently linked single-stranded RNA molecules joined at their ends, resulting in a loop shape. This covalent link is considered to contribute significantly to their stability, as most RNA-degrading enzymes require an open end to initiate degradation. Upon analysis of a circular RNA–specific RNA-seq study that sequenced RNA across different life stages until aging, four circular RNAs of two different genes were identified to accumulate extensively during aging. CRISPR/Cas9 was then utilized to specifically silence selected circular RNAs by targeting their circularization, and the effects of these deletions on C. elegans longevity were investigated.
İki-boyutlu yarı iletkenlere dayalı nano-cihazların tasarımı ve taşıma özellikleri
As the semiconductor industry approaches the fundamental physical and electrostatic limits of traditional silicon-based transistors, the transition toward atomically thin channel materials has become imperative to sustain technological scaling. This thesis presents a proof-of-concept study on the design and transport properties of nano-devices based on two-dimensional (2D) semiconductors by evaluating their feasibility as a modular platform for next-generation nanoelectronics. Utilizing a comprehensive first-principles and quantum transport-based computational methodology that combines Density Functional Theory (DFT) with the Non-Equilibrium Green's Function (NEGF) formalism, the research systematically evaluates device performance under the ballistic transport limit. This investigation starts with Metal-Semiconductor-Metal (MSM) systems to clarify how channel length and electrode doping govern current flow at nanometer scales. The analysis then advances to p-n junctions to capture the influence of built-in electrostatics on tunneling-driven rectification. The study is followed by p-i-n field-effect transistors as intermediate architectures where gate electrodes serve as active control elements. Finally, the study is finalized with the assessment of MOSFET architectures where the integrated effects of contacts, channel transport and electrostatic control are evaluated within a unified device concept. It is evaluated that architectural optimization is as critical as material selection in the deeply scaled 2D regime. In particular, underlap engineering is identified as a practical instrument to tune source and drain electrostatics and screen drain-induced field penetration without altering the intrinsic channel material. The results demonstrate that incorporating such optimized geometries significantly boosts on-state currents and improves energy efficiency. Furthermore, these improvements enable devices to meet or surpass ITRS-2028 high-performance targets. Ultimately, this thesis presents prototype devices that demonstrate the extraordinary potential of 2D semiconductors for high-performance transistor operation when their atomically thin nature is paired with precise electrostatic engineering.
Beyindeki kompleks ağları analiz etmek için graf teorisi
The brain is a large-scale, intricate web of neurons, known as the connectome. By representing the brain as a network i.e. a set of nodes connected by edges, one can study its organization by using concepts from graph theory to evaluate various measures. We have developed BRAPH - BRain Analysis using graPH theory, a MatLab, object-oriented freeware that facilitates the connectivity analysis of brain networks. BRAPH provides user-friendly interfaces that guide the user through the various steps of the connectivity analysis, such as, calculating adjacency matrices, evaluating global and local measures, performing group comparisons by non-parametric permutations and assessing the communities in a network. To demonstrate its capabilities, we performed connectivity analyses of structural and functional data in two separate studies. Furthermore, using graph theory, we showed that structural magnetic resonance imaging (MRI) undirected networks of stable mild cognitive impairment (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and Alzheimer's Disease (AD) patients show abnormal organization. This is indicated, at global level, by decreases in clustering and transitivity accompanied by increases in path length and modularity and, at nodal level, by changes in nodal clustering and closeness centrality in patient groups when compared to controls. In samples that do not exhibit differences in the undirected analysis, we propose the usage of directed networks to assess any topological changes due to a neurodegenerative disease. We demonstrate that such changes can be identified in Alzheimer's and Parkinson's patients by using directed networks built by delayed correlation coefficients. Finally, we put forward a method that improves the reconstruction of the brain connectome by utilizing the delays in the dynamic behavior of the neurons. We show that this delayed correlation method correctly identifies 70% to 80% of the real connections in simulated networks and performs well in the identification of their global and nodal properties.
Kademeli-indeks çok modlu fiberlerde uzaysal-zamansal doğrusal olmayan dinamikler
Spatiotemporal pulse propagation in multimode fibers is generally considered as chaotic. Graded-index multimode fibers reduce the complexity due to its equal spacing of the modal wave numbers which also introduces a periodic self-imaging to the propagating beam. This unique phenomenon affects the coupling between the modes thus graded-index multimode fibers are an ideal testbed to study spa- tiotemporal pulse propagation. In this thesis, various spatiotemporal nonlinear dynamics studied in graded-index multimode fibers to achieve wavelength con- version, supercontinuum generation triggered by cascaded Raman scattering and to develop a novel all-fiber all-normal dispersion mode-locked laser cavity. In normal dispersion regime, spatiotemporal instability of femtosecond pulses discovered numerically and experimentally by exciting a graded-index multimode fiber with a Ti:Sapphire laser capable to generate 200 fs pulses at 800 nm. With 90 THz frequency shift, Stokes and anti-Stokes sidebands are observed. The signature of spatiotemporal instability which allows the sidebands to inherit the spatial distribution of the pump pulse is observed with the spatial characterization of the generated sidebands. Later a high power laser system with adjustable output parameters is devel- oped as a pump source for spatiotemporal nonlinear pulse propagation studies. By employing this source, with MHz pump pulse repetition rate high power octave- spanning supercontinuum generation triggered by cascaded Raman scattering is demonstrated. The results obtained with this novel method is the highest aver- age power and repetition supercontinuum source with a standard graded-index multimode fiber in the literature. Additional spatiotemporal wavelength conversion mechanisms, a small graded- index multimode fiber between single mode fiber segments can be used as a bandpass filter and saturable absorber. These effects are combined in an all- fiber all normal dispersion laser cavity for the first time in the literature. In the demonstrated cavity design, mode-locking is achieved by nonlinear multimodal interference in graded-index multimode fiber segment. All-normal cavity design supports dissipative soliton pulse formation but it requires bandpass filtering. This requirement is satisfied with multimode interference reimaging thus a unique and simple all-fiber cavity design is constructed to generate ultrashort dissipative soliton pulses. The developed oscillator generates 5 ps pulses at 1030 nm with 44 MHz repetition rate. These pulses are externally compressed to 276 fs. All-fiber cavity design ensures stability and 70 dB sideband suppression is measured in radio frequency domain.
Koloidal kuantum kuyularının sentezi ve karakterizasyonu: Basit boyutları ayarlanabilir çekirdekliden karmaşık çoklu taçlı yapılara
As a new class of semiconductor nanocrystals, colloidal quantum wells (CQWs), also commonly known as nanoplatelets (NPLs), exhibit remarkable electronic and optical properties that will potentially find a wide range of use from nanophotonics to optoelectronics. NPLs feature step-like absorption profiles and discrete emission spectra with giant oscillator strength resulting in high recombination rates. All these features make these atomically-flat structures highly attractive for light-harvesting and -generating applications. In this thesis, to understand the size-tuned properties of their two-dimensional architecture, we conducted a systematic study on the core-only NPLs by using a set of 4 monolayer (ML) CdSe cores as our working model and carefully altered their aspect ratio while keeping their lateral area constant. In such a core-only NPL structure, electron and hole are both confined in the core resulting in type-I electronic band alignment. By decreasing the width of these NPLs to a value comparable to or less than their exciton Bohr radius, we observe additional confinement effects emerge. Subsequently, by growing CdSe1−xT ex alloyed crown around these starting 4 ML CdSe cores, we find type-II electronic band alignment is obtained. Thanks to their spatially indirect excitons, these core crown NPLs show extraordinarily long radiative lifetimes. Moreover, with the increased absorption cross-section owing to their added crown, high-performance optical gain is achieved via their core/crown heterostructure. However, in this form, their usage is limited since they are unstable in solution forming gels and they exhibit strong tendency to form stacks in films. To address this problem, here we proposed and developed a multi-crown architecture by additionally growing a CdS crown around the periphery of the typeII heterostructure, enabling excellent optical gain media with enhanced stability. The structural and optical characterizations of the synthesized multi-crown NPLs indicate that this complex architecture holds great promise for making devices in colloidal nanophotonics and optoelectronics.
Motor kayganlaştırıcı yağların bozunma izlenimi için triboelektrik şarj etkisinin kullanılması
Lubrication of machine parts is necessary to prevent friction and wear in machine operation. Even the slightest reduction of friction and wear cause a huge positive impact in the economy since almost all machines in our current industry suffer from the energy and material losses caused by these events. Therefore, maintaining good and stabilized lubrication is vital for this purpose. However, oxidation of lubricants upon operation brings about unwanted changes in its chemical and physical properties and causes lubrication performance to deteriorate. Thus, a better understanding of lubricant condition and its variation under different parameters can enable technologists to make informed decisions to ensure lubrication excellence and optimization of the lubricant's renewal time. However, current methods for detection of oil deterioration lack practicality and flexibility. In this study, a novel method was put forward to estimate the remaining service life of several types of commercially available engine lubricants using triboelectric cation. A Triboelectric sensor (TES) was developed and this TES was given different open circuit voltage (Voc) values according to the different oxidation time of lubricant oils. These results were then correlated with FTIR-ATR analyses of the oils. Additionally, we reported the dynamic viscosity changes of engine oil samples upon oxidation. We believe the results presented in this thesis convey the basis for establishing a TES for straightforward detection of deterioration of engine oil.
Yüklü nanoparçacıkların elektrostatik kuvvetler ile akışkan ortamda yönlendirilmesi
Deposition of nanoparticles in a controlled manner is suitable for the application of unique properties of nanoparticles in designing novel electronic devices. Printing different types of nanoparticles on the same surface generates multifunctional surfaces and opens up possibilities to elaborate future devices. Electrostatic forces can potentially be utilized to manipulate different types of materials such as magnetic, insulating, conducting, semiconducting, organic and inorganic materials. Moreover, chemistry of materials and the surface is not altered. Herein, we applied these forces to direct and position charged nanoparticles on desired areas of the surface from nonpolar and aqueous dispersions. Assemblies of particles are obtained on both nonconductive surface with charged patterns and on metallic nano- and microstructured electrodes. Arrays of gold electrodes of sizes from 500 nm to 50 µm were prepared by using the conventional fabrication techniques such as photolithography, electron beam lithography, thermal evaporation and lift off. Charge patterns are formed on 100 nm PMMA surface which is coated on the electrodes to provide electrical contact. An external voltage was applied and substrate was immersed into desired aqueous negatively charged colloidal gold dispersion to direct nanoparticles on aforementioned charge patterns. The next step was to attract two different charged nanoparticles towards different locations on the same substrate by means of electrophoretic deposition. Assemblies formed from positively charged silver nanoparticles and negatively charged fluorescent latex and silica nanoparticles are demonstrated. Last but not least, composite structures were obtained with similar techniques in order to increase the functionality of the structured surface. To achieve this goal, different types of nanoparticles were coated on top of each other without changing the location of electrodes. The shape of these composite structures is controlled by the electrode geometry.
Vo 2 kristal büyütmesı ve hidrojen ile katkılanmasının üzerine incelemeler
Vanadium Dioxide(VO 2) has been studied extensively for its interesting electronic structure that allows it to go through Metal-Insulator Transition(MIT) at 65◦C. The nature of this phenomena is not entirely clear and more research is needed to firmly establish the science behind it and to realize possible applications; such as ultra-fast electrical and optical switching, sensor devices and Mott-Field Effect Transistors. One of the important experiments to understand the electronic structure of a material is Hall-effect measurements but due to acicular (needle like) nature of VO 2 crystals, this subject is only studied either on millimeter sized samples which are not suitable for many device applications or on poly crystalline thin films that are under non-uniform stress due to the substrate effects which gives unsatisfactory results when performing experiments. This thesis suggest a new method of chemical vapour deposition(CVD) growth for low aspect ratio VO 2 crystals that have lengths between 50-100 μm and thicknesses between 40-170 nm. These crystals can be mechanically removed from the substrate and transferred to use in different applications such as Hall-effect measurements or Transmission Electron Microscope(TEM) studies. Additionaly this work shows some aspects of the surface chemistry of the widely used Silica, Si, quartz and Sapphire substrates; relating with the control of oxygen saturation on the surface. Another VO 2 growth method for c-plane sapphire that leads to considerably more crystal yield is shown. Hydrogenation of the VO 2 crystals suppresses the MIT so understanding this phenomena might help us better understand the effects lying behind the transition. To study this phenomena a crystal is doped only from half by blocking the passage of hydrogen to other half so the interplay between the insulating phase and hydrogenated conductive phase can be observed. As the analysis tool, TEM is used on this sample. Using a two-terminal device of a VO 2 crystal, the effects of hydrogenation on the electronic properties have also been studied. Overall this thesis introduces a new method for CVD growth of VO 2 which is used in various applications such as Hall-effect experiments, two terminal devices and TEM studies. To control the growth process the interplay between oxygen and surface chemistry of sapphire, silica, Si and quartz substrates have been investigated. With these studies a better understanding of the mechanics of growth is intended.
Biyomedikal ve yenileyici tıp uygulamalarında kullanılan nanomalzemelerin moleküler seviyede incelenmesi
Molecular mechanisms are inspiration source for effective nanomaterial synthesis through minimalist bottom-up approaches. Mimicking functional bio-physicochemical properties of biomacromolecules can give new insights for design and synthesis of nanomaterials used in biomedical and regenerative medicine applications. In this thesis, rationally-designed nanomaterials and their biomedical applications as oral ketone delivery and biomineralization and long-term potential toxicities were investigated. In the first chapter, basic concepts of nanomaterial design, synthesis, characterization, and nano-bio interface were explained. In the second chapter, a novel long-term nanoparticle accumulation model was developed to understand active regulation of nanoparticle uptake, nanoparticle accumulation behavior and the impact of long-term exposure on cellular machineries (e.g. ER stress). In the third chapter, the role of ketone body betahydroxybutryrate (βOHB) generated by a metabolic enzyme, hydroxymethylglutaryl CoA synthase 2 (HMGCS2), on intestinal stem cell maintenance and regeneration after radiation injury was investigated. Consequences of βOHB depletion in intestine were rectified by oral delivery of PLGA-encapsulated and oligomer forms of βOHB. The last chapter, acidic epitopes of enamel proteins (e.g. amelogenin) were integrated into self-assembling peptides to remineralize eroded enamel. Overall these studies show potential of nature-inspired engineered nanomaterials in vast range of biomedical and regenerative medicine applications.
Koloidal atomik katman kaplama ve sıcak enjeksiyon kabuk kaplama yöntemlerinin birleşimiyle geliştirilen yarı iletken nanolevha heteroyapıları
One of the most promising families of semiconductor nanocrystals in colloidal optoelectronics and nanophotonics is considered to be colloidal quantum wells, also commonly referred to as nanoplatelets (NPLs). Possessing an atomically flat structure, NPLs feature unique properties including spectrally-resolved and tunable light-hole- and heavy-hole transitions accompanied by their respective giant oscillator strengths. CdSe, CdS and CdTe, making the first colloidal NPLs synthesized in core-only structure, portray distinct qualities necessary for light-harvesting and -generating applications. However, going beyond the core structure, there are many properties that are highly enhanced by growing crown and/or shell layers around core NPLs. While the crown growth takes place anisotropically in lateral directions, the shell layer covers the entire NPL surface, combinations of which enable NPL heterostructures in new architectures. Depending on the electronic alignment of parts of the NPL heterostructure and the resulting confinement of electron-hole wave functions, these hetero-NPLs can be type-I or type-II. In type-I electron-hole pairs are confined in the core-NPL and recombination occurs in a direct pathway. In type-II electron-hole wave function is separated into different semiconductor layers, resulting in spatially indirect recombination. In this thesis, we synthesized and showed thin- and thick-shell grown heterostructures of type-I CdSe/ZnS NPLs using hot-injection (HI) for the first time particularly for these semiconductor NPLs. Unlike the typical colloidal atomic layer deposition (c-ALD) technique, which produces NPL heterostructures with low quantum yield (QY) and low chemical and optical stability, our approach yields CdSe/ZnS NPLs of almost unity (100%) quantum yield (QY) and improved chemical stability, tested by washing the same samples rigorously up to 6 times with ethanol with little change observed in the QY. Additionally, unparalleled thermal and optical aging endurances is achieved in aging tests. These tests experimentally demonstrated that, elevated to 400 K, HI thick-shelled NPLs can retain up to 65% of their emission intensity in the colloidal form and 52% of that in the film. This level of high stability creates a great opportunity for employing these NPLs for high-temperature applications. Also, in the thesis, we synthesized and studied CdS/CdSe core/crown, CdS/CdZnS core/c-ALD shell-grown and CdS/CdSe/CdZnS core/crown/c-ALD shell-grown heterostructures of NPLs. Here the starting-template CdS NPLs are considered to be unique in terms of their emission in the blue region, which may open up new opportunities for NPL lasing in this spectral region. Nominally CdS NPLs are folded due to great lateral sizes. However, in this research work, when coated with crown and shell layer, these particles unfold. The unrolled CdS/CdSe core/crown NPLs are found to exhibit relatively higher QY up to 15-20% in its class of CdS core-seeded NPLs. The findings of this thesis reveal that such heterostructures of the NPLs are very rich in terms of variety of the quantum architectures one can achieve using them as working model systems.
Dengeden uzak, dinamik, adaptif kolloidalkristaller
Self-assembly has been the center of attention of many researchers from all branches of science. Self-assembly of static structures such as crystals often forms through energy minimization, while dynamic ones need constant energy flow to maintain their state. Most of the studies on self-assembly are limited to static self-assembly, and despite its ubiquity in nature, our comprehensions of dynamic self-assembly are still in its infancy due to lack of experimental settings that can keep the system in its dynamical state. In 2017 a state-of-the-art dissipative (dynamic) self-assembly method was introduced by S. Ilday, and co-workers (Nature Commun., 2017). Here, using this method, we studied the formation of dynamic adaptive colloidal crystals far from equilibrium. We use a femtosecond laser as an energy source to drive a quasi-2D confined colloidal system far from thermodynamic equilibrium, and for the first time, we observed the formation of a rich set of dynamic adaptive colloidal crystals of tens to hundreds of units of polystyrene spheres, which interact through hydrodynamic and hard-sphere interactions. We report formation of periodic 2D Bravais lattices, Moiré patterns, honeycomb lattices and aperiodic quasicrystals. Furthermore, we identify, analyze, and verify some of the key experimental parameters, e.g., physical boundaries, thickness of the liquid film, and the average velocity of Brownian motion, affecting the formation of such a variety of colloidal crystals. We anticipate this study to be a starting point to uncover the physical principles behind the emergence of patterns from simple parts.
Antibakteriyel fotodinamik tedaviye yönelik hibrit çekirdek-kabuk nanoparçacıklarının tek adımda sentezi
Multidrug resistance (MDR) in Escherichia coli (E. coli) has become a worrying issue that is not only increasingly observed in humans but also is widespread in veterinary medicine worldwide. Therefore, developing new and effective alternatives to conventional antibiotics has become an imperative need. The idea of using photodynamic therapy (PDT) for bacterial eradication is a solution for the cases that the bacteria are resisting to conventional antibiotics. Although in these cases, PDT can be an option, PDT-killing efficiency might still not be sufficient, and some enhancements are necessary. Metal-enhanced singlet oxygen generation (ME1O2) is one of the ways to enhance the PDT-killing efficiency of the E. coli. Hybrid core-shell structures can serve conveniently for this purpose. These structures can combine the flexible and tailorable features of polymers (shell) with the photophysical properties of plasmonic metals (core). In this work, using gold as a core and conjugated oligomer as a shell produced a novel hybrid core-shell nanoparticles which can enhance the singlet oxygen generation capacity and subsequently, improve the PDT-killing efficiency of the E. coli. In this structure, the shell is responsible for the spontaneous reduction of gold ions, forming gold nanoparticles and protecting them from the aggregation. With further investigation and optimization, the hybrid core-shell nanoparticles with the help of ME1O2 successfully improved the killing efficiency of E. coli bacteria by 40%.
Biyomedikal uygulamalar için teşhis ve tedavi biyo-aracı
Biological systems are programmable by their nature. With using the abilities of these systems, scientists have designed, engineered and repurposed living machines for various tasks including biological sensing, recording of cellular events, drug production and disease treatment. Compared to the current methodology for these tasks, engineering biological systems provide a promising tool for the future of medicine, especially in the case of disease treatment. Type II Diabetes Mellitus (T2DM) is a medical condition which occurs by the deficiency of insulinotropic hormones inside the body and affects nearly half a billion people worldwide. Treatment strategies for this disease include monitoring patient for blood glucose levels, fine production of insulinotropic hormones and providing dose-controlled treatment for the patients. All these operations increase the cost of the treatment and cause a global problem for both medical professionals and patients. In this thesis, we propose novel systems for developing theranostic strategies for T2DM by using synthetic biology principles and genetically controlled sense-and-response cascades inside living cells. Proposed systems include a whole-cell glucose biosensor module, which can detect glucose concentrations by using internal glycolysis machinery of a probiotic Escherichia coli (E. coli) bacteria, and a release module, which can controllably secrete therapeutic molecules from the E. coli cell surface. To do that, we engineered an enzyme-based biosensor module which takes the pyruvate synthesized as a result of glycolysis and turns that molecule into hydrogen peroxide via SpxB pyruvate oxidase enzyme to later detect that signal with an optimized hydrogen peroxide biosensor. In order to later incorporate this biosensor with a release mechanism, we designed and engineered an Antigen-43 (Ag43) autotransporter based peptide release system. In that system, we used Ag43 autotransporter fused GLP-1 peptide, an insulinotropic hormone for the type II diabetes treatment that is controllably displayed on the cell surface. Another Ag43 fused protein, TEV protease, with a different control mechanism is also cooperated in the system to release GLP-1 from the surface by cutting the peptide from its recognition site. Taking the ability of glucose sensing and the successfully engineered release mechanisms, our proposed system has a huge potential to be used as an alternative system for treatment of the T2DM.
Glikozilasyon: Protein tabanlı malzeme geliştirmede yeni bir araç
Biofilms are bacterial communities formed by adhesion of cells to each other via extracellular matrix. Proteins, one of the components of biofilm matrix, can form fibers and have properties enabling their use as materials. Bacillus subtilis biofilm major protein TasA is a fiber forming non-amyloidogenic protein providing biofilm rigidity. Glycosylation is a post-translational modification observed in all domains of life where sugar groups are added on proteins covalently. Campylobacter jejuni glycosylation is the first bacterial N-linked glycosylation discovered and the most studied system where a heptasaccharide is attached to protein. C. jejuni glycosylation has variety of functions among adhesion, protease resistance and thermal stability. Glycosylation may become an additional method for engineering biofilm proteins as materials with unique properties. For this purpose, we examined effect of glycosylation on structure of natively non-glycosylated proteins by glycosylating alkaline phosphatase enzyme (ALP) at different locations on the protein. Interestingly, phosphatase activity assay showed slight increase in ALP activity on pure proteins glycosylated at the C-terminus. Next, TasA protein was glycosylated at the C-terminus. Glycosylation had no significant effect on fibrillation of TasA in vitro. Secondary structure analysis using circular dichroism data revealed shift from antiparallel to helix structure with glycosylation. Quartz crystal microbalance experiments indicated increased adhesive properties on glycosylated TasA protein on gold. Its application possibility as cell adhesive was assessed by visualizing surface coverage of polystyrene cell culture plate under scanning electron microscope. As a consequence, glycosylation was used as an engineering method for protein-based material development for the first time.
Patojenik amiloidler için aday ilaç peptitleri
Amyloid fibrils are very stable, ordered cross-β structured, resistant to protease degradation, proteinaceous composits. All amyloids have different peptide/protein sequences although they express similar structural properties. Some of amyloids possess advantageous functionalities such as protection, cell-cell communication, protein storage. However, most of amyloids are associated with various severe diseases such as neurodegenerative diseases. Although amyloids follow similar formation pathway, pathogenic amyloids are challenging since their formations are supported with secondary pathways. Up to now, there were several therapeutic approaches that are only effective in symptoms of disease conditions by masking or slowing down the symptom developments. Nonetheless, different approaches are developed for inhibiting amyloid aggregation. Today, most of the strategies are aiming to inhibit secondary nucleation, which is not fully understood yet. So, such approaches can be faced with lots of challenge in terms of secondary nucleation kinetics and formation mechanism. Thus, inhibition of monomeric amyloid units, which are developed into amyloid aggregates, can be another novel approach for halting disease-condition developments. In this thesis, candidate ligand peptides that cease aggregation of huntingtin, α-synuclein and amyloid-β were selected by using different types of display systems, which are bacterial surface display, yeast surface display and phage display. The monomeric amyloid units of these proteins were expressed on surfaces of bacterial cells and yeast cells in order to expressing monomeric units with a proper folding and avoiding aggregation after expression without interacting with each other. Candidate ligand peptides were selected against neurodegenerative amyloids by M13 phage display library. First, M13 phage display library was tried to be produced from using wild type M13 bacteriophage by basic cloning methods as well as commercially available M13 phage display library kit was used for peptide selection since the minor coat protein pIII of M13 is widely used for peptide display and ligand peptide selection studies. Thus, 12 amino acid-long peptides displayed on the minor coat protein pIII were selected against neurodegenerative amyloids for inhibiting protein aggregation purpose in the very first step of aggregation pathway.
Mikroakışkan akış sitometrisi uygulamarında viskoelastik parçacık hizalama tekniğinin geliştirilmesi
Advances in cell biology, quantification, and identification procedures are essential to develop novel particle characterization tools on the diagnostics, biotechnology, pharmaceutical industry, and material science. Flow cytometry is a pivotal technology and meets the need for almost a century. An increase in today's demand for fast, precise, accurate, and low-cost point-of-care diagnostic tools and cell counting technologies necessitate further improvements for state-of-the-art flow cytometry platforms. These improvements are achievable using novel and precise particle focusing techniques, multiple detection methods, integrated fluidic, optical, and electronic units in the same workflow. Thanks to its indisputable advantages in such integrities, microfluidic flow cytometry platforms are attractive and promising tool for the future of next-generation flow cytometry technologies. In this thesis, we developed viscoelastic focusing technique compatible with optical, impedimetric, and imaging-based microfluidic flow cytometry methods. Elastic nature of the viscoelastic fluids induces lateral migration for suspended particles into a single streamline and meets the requirement for central particle focusing on flow cytometry devices. Viscoelastic focusing is a passive particle manipulation technique and eliminates the need for sheath flow or any other active actuation mechanism. Firstly, we developed viscoelastic focusing technique for optical microfluidic flow cytometry in a palm-sized glass capillary device. Optical detection was performed by fiber-coupled laser source and photodetectors. We demonstrated the detection of polystyrene (PS) cytometry calibration beads suspended in three viscoelastic solutions: Polyethylene oxide (PEO), Hyaluronic acid (HA), and Polyvinylpyrrolidone (PVP). Secondly, we investigated the viscoelastic focusing efficiency of PEO-based viscoelastic solutions at varying ionic concentrations to demonstrate their use in impedance-based microfluidic flow cytometry. We performed cytometry measurements using PS beads and human red blood cells (RBCs). We showed that elasto-inertial focusing of PS beads is possible with the combination of inertial and viscoelastic effects for high-throughput flow cytometry applications. Additionally, non-spherical shape RBCs were aligned along the channel centerline in parachute shape, which yielded to decrease the non-spherical shape-based signal variations in impedance cytometry devices consistent impedimetric signals. Our results showed that proposed flow cytometry devices give similar performance to state-of-the-art systems in terms of throughput and measurement accuracy. Optical- and impedance-based flow cytometry applications were demonstrated using only pressure-driven flow. Under the simultaneous use of pressure-driven flow and DC electric field, particles inside microfluidic channels exhibit intricate migration behavior at different particle equilibrium positions. Available experimental and analytical studies fall short in giving a thorough explanation to particle equilibrium states. Also, the understanding is so far limited to the results based on Newtonian and neutral viscoelastic fluids. Thirdly in this thesis study, a holistic approach is taken to elaborate the interplay of governing electrophoretic and slip-induced/elastic/shear gradient lift forces. Experimental studies were carried on particle migration in Newtonian, neutral viscoelastic, and polyelectrolyte viscoelastic media to provide a comprehensive understanding of particle migration. Our experiments with the viscoelastic media led to contradictory results with the existing explanations. Then, we introduced the Electro-Viscoelastic Migration (EVM) theory to provide a unifying explanation for particle migration in Newtonian and viscoelastic solutions. Additionally, we performed confocal imaging experiments with fluorescent-labeled polymer solutions to explore the underlying migration behavior in the EVM technique. We observed the formation of cross-sectionally non-uniform viscoelastic solution would pave the way for undiscovered unique applications in the microfluidic community. In summary, presented devices were demonstrated with straightforward fabrication techniques on a single straight microcapillary or microchannel. It is possible to couple fluidics, optical, and impedimetric detection units into the same workflow. Our approach in microfluidic flow cytometry applications proved that viscoelastic fluids are good candidates for the development of integrated, portable, and cost-efficient next-generation cytometry platforms and low resource settings. Additionally, the unifying EVM technique has a strong potential to precisely focusing and separating cells, polyelectrolytes, DNA fractions, and proteins according to their charge and size with a comparable resolution and measurement time as a replacement for gel electrophoresis or chromatography applications.
Gıda katkı maddeleri ve ilaçların elektroeğirme yöntemi kullanılarak üretilen ve siklodekstrin molekülü ile fonksiyonlaştırılmış nanolifler ile enkapsülasyonu
Electrospun nanofibers attract attention of many areas including food and pharmaceutical industries thanks to their unique physical/mechanical properties like large surface area-to-volume ratio, nanoporous structure, design flexibility and lightweight. Although, in general polymers are used for fabrication of electrospun nanofibers, it is also possible to obtain electrospun nanofibers purely from cyclodextrins (CDs). CDs with truncated cone shape structure are attractive host molecules for the formation of host-guest type inclusion complexes (ICs) with variety of appropriate guest molecules. Creating ICs with CDs causes remarkable enhancement at the properties of the guest molecule, and so CDs have wide range of applications in many areas including food and pharmaceutical industries. In this thesis, polymer-free electrospun nanofibers from CD-ICs of some food additives and drugs were produced. Firstly, four food additives, menthol, carvacrol, cinnamaldehyde and beta-carotene were encapsulated by electrospun CD nanofibers. Afterwards, the solubility, heat/light stability, antibacterial/antioxidant activity of the materials were investigated to observe the effects of encapsulation by CD nanofibers on the food additives. Secondly, electrospun CD-IC nanofibers of three types of drugs, sulfisoxazole, paracetamol and catechin were produced. Since one of the most critical point for drug bioavailability is its solubility in water, the obtained electrospun drug/CD-IC nanofibers were mainly investigated in terms of change in their solubility. In the light of analyses, it can be concluded that, main drawbacks of food additives and drugs like high volatility, low solubility and low stability were reduced or removed; besides, their properties such as antioxidant and antibacterial activities were enhanced or preserved.
Çeşitli nanotıp uygulamaları için kükürbitüril tabanlı supramoleküler yapılar
The supramolecular chemistry of cucurbiturils (CBs) has been rapidly advancing to span wide range of nanomedicine applications including but not limited to pharmaceutical drug formulation and delivery, bio/medical imaging and sensing, cancer therapy, tissue engineering, development of antibacterial/antiviral agents and protein modification. Owing to unique recognition properties and low cytotoxicity, the supramolecular assemblies of CBs are particular promises for biomedicine tasks. Inspired by these developments, three multifunctional supramolecular constructs of CBs containing photoactive conjugated compounds were prepared to be utilized in nanomedicine applications covering antimicrobial and anticancer photodynamic therapy (PDT), combined PDT and photothermal therapy (PTT) for the inactivation of bacteria, drug delivery and cellular imaging. A stable rotaxane, namely [5]-rotaxane, based on photoactive alkyne-substituted porphyrin and azide-substituted stopper group was synthesized through 1,3-dipolar cycloaddition reaction. Herein, cucurbit[6]uril (CB6) acts as both macrocycle and catalysis for the reaction and encapsulates formed triazole ring inside its cavity. [5]-rotaxane was further investigated and results revealed that it has ability to generate reactive oxygen species (ROS) including singlet oxygens in high yield even under quite low fluence of light and short exposure time and this, in turn, renders it ideal photosensitizer which remains stable at physiological pH (7.4) for prolonged times. By taking the advantages of aforementioned properties, [5]-rotaxane was employed as a broad-spectrum antibacterial agent against Gram-negative and Gram-positive bacteria as well as anticancer agent against human breast cancer cell line (MCF-7) via visible-light-induced generation of ROS. [5]-rotaxane possess negligible dark cytotoxicity upon complexation with CB6 and it can afford efficacious PDT of cancer and infectious diseases caused by bacteria. Another multifunctional photoactive supramolecular assembly was built through covalently binding of four cucurbit[7]uril (CB7) molecules, functioning as receptor, to a tetraphenyl porphyrin core using suitable linkers. In addition to its light-promoted antibacterial property, here, main objective was to combine chemo- and photodynamic cancer therapy which makes this study novel. Presence of CB7, enables host-guest interactions with anticancer drug, doxorubicin hydrochloride (DOX), and therefore this system was used to carry drug molecules achieving synergistic PDT and chemotherapy. Finally, CB7-capped hybrid nanoparticles (NPs) made up of red-emitting conjugated oligomer (COL) and gold nanoparticles (Au-NPs) were obtained through one-pot synthetic method. These hybrid NPs were found to own high photostability, thermal reversibility and high ROS generation capacity. Benefitting from these properties, combined photodynamic and photothermal killing efficiency of NPs towards Gram-positive and Gram-negative bacteria was verified. Additionally, cellular imaging capability of them was shown owing to their inherently fluorescent characteristics and this feature could be utilized for image-guided PDT applications.
Geçiş metal dikalkojenitlerinin optoelektronik ve termal özellikleri
After the successful isolation of graphene from its bulky counterpart, there has been tremendous advancement in the fi eld of 2D material. Transition metal dichalcogenides(TMDCs) is family of 2D materials comprising of a transition metal atom sandwiched between two chalcogen atoms. Photoresponse of semiconducting TMDCs has been studied extensively in literature. However, photoresponse from metallic TMDCs is unprecedented and hence has not been studied to explore which mechanism might prevail. Among our fi ndings, we discovered that photocurrent generation through metallic TMDCs is possible and has a photo-thermal origin. Using scanning photo-current microscopy, we were able to obtain spatial photocurrent maps for both, zero biased and biased samples. At zero applied bias, the photocurrent generation is localized to metal-metal junction and governed by Seebeck effect. At fi nite applied bias, photocurrent from the whole crystal is observed and is due to photobolometric effect. As Photo-bolometric effect relies on photo-thermally induced resistance change of the material, we extended our study to extract thermal conductivity of metallic TMDCs via bolometric effect. As contact of crystal with substrate act as a heat sink, we used suspended crystals over a hole to thermally isolate it from any heat sink. Resistance change via laser induced heating is experimentally measured at the center of the suspended part of crystal. Measured resistance change is matched with expected resistance change which is calculated using thermal conductivity(k) as a fitting parameter via commercially available fi nite element method package(COMSOL). This way, thermal conductivity of the metallic TMDCs is calculated with very high accuracy and precision.
Eşdağılımlı mikroakıskan damlacık olusumunun analizi ve biyokimyasal uygulamaları
Droplet fluidic systems have dramatically improved precision in many applications, such as polymerase chain reaction, biochemical analysis, and particle synthesis in which accurate control of sample volume plays a significant role. Despite the well-understood physics of squeezing regime droplet formation in two-phase flow systems, the long-sought-after goal of generating identical, equal size droplets is challenging. Although the individual parameters that affect the droplet size were identified as channel dimension, wettability, viscosity, and flow rate or pressure ratio of the two immiscible fluids, the governing mechanism of droplet size variation is not completely analyzed. More importantly, the limit of monodispersity for droplet generation systems is still unknown. This is due to the difficulty in analytical modeling of droplet formation that is usually compensated by experimental approaches, which fall short in leading to universal conclusions. In this thesis, depending on the flow source used for driving fluids we present an analytical approach that takes into account all the system dynamics and internal and external factors that disturb monodispersity. We use the analogy between fluidic and electrical circuits to analyze the factors that influence droplet monodispersity. Interestingly, we enable to model the dynamics of a segmented two-phase flow system using a single-phase flow analogy, electron flow, in electrical circuits. Doing so, we reveal the sources of disturbances that lead to variation in droplet volume. We offered a unique solution and designed guidelines to ensure ultramonodisperse droplet generation. Our analytical conclusions are experimentally verified using a T-junction and flow-focusing droplet generator design driven by a pressure supply. Equally importantly, we show the limiting experimental factors for reaching the theoretical maximum of monodispersity. For the displacement pump case, we propose a more effective and widely applicable solution to improve flow stability, by controlling off-chip compliances to minimize fluctuations due to the flow source. Eventually, we compare the performance of the two common drive units (pressure-driven and displacement pump) in terms of droplet monodispersity, while using our proposed methods and guidelines. Finally, we did study in reaction kinetics of poly dopamine and hydrogen peroxide and synthesize silica and polyethylene glycol (PEG) particles and supramolecular polymer capsules with high monodispersity using ultra-monodisperse droplets.
Tek tabaka grup V sistem ve bileşiklerinin fonksiyonelleştirilmesi: Alaşım, katkı ve yüzey modifikasyonu
There has been growing interest during the last decade in two-dimensional (2D)materials due to their important roles in various scientific and technological applications such as detectors, lasers and light emitting diodes. In this thesis we present a theoretical investigation of a couple of such 2D materials from group V monolayers and their compounds. Firstly, ordered alloys of GaxAl1−xN hexagonal monolayer are studied and the effect of Al content on mechanical, electronic, thermal and optical properties are investigated. The optimized lattice constants and band gaps change in accordance to Vegard's Law. Low barrier energies and favorable substitution of Ga by Al may show feasibility of fabrication. Segregation is also checked with mixing energy calculations. The dynamical stability of alloys is shown by phonon spectrum analysis and MD simulations. GaxAl1−xN alloys give lower in-plane stiffness than h-BN or graphene, but higher Poisson's ratio than most realized 2D systems. Heat capacity of alloys delivers a decrease with Al content at low temperatures but it converges to the classical limit at high temperatures. The absorption onset of GaxAl1−xN alloys remain in the near UV range and prominent absorption peaks blue-shifts with increasing x in compliance with the variation of the band gap. The considered systems, in regard to their stability and tunable fundamental properties seem to be very promising 2D semiconductors for wide range of applications at reduced scales. Then, the interaction of alkali metal atoms (Li, Na, and K) with single layer and periodic structures of hb-As and sw-As phases are revealed by first-principles methods. Arsenene phases are considered to be used as electrodes (anode) for ion-batteries. Strong alkali-electrode binding and low diffusion energy barriers gives out better cycling stability and faster diffusion, respectively. hb-As shows better storage capacity than sw-As. However, deviations from ordered pattern and decline of formation energy with increasing doping level point out a possible structural transformation. By MD calculations, crystalline to amorphous phase transition is seen even for low concentrations level at ambient temperature. The average open-circuit voltages of 0.68-0.88 V (0.65-0.98 V) with specific capacity up to 715 mAhg−1 (358 mAhg−1) are calculated for single layer (periodic) configurations. Overall, non-crystalline phases are calculated to offer more favorable structures than crystalline configurations and they provide more coherent results when compared with experimental data. The obtained voltage profile together with low diffusion barriers and strong metal-electrode binding suggests arsenene as a promising anode material to be used in for alkali-ion battery applications. Lastly, the formation of dumbbell (DB) geometry upon adsorption of Ga, N adatoms to GaN monolayer is investigated. While Ga-N DBs are unstable, Ga-Ga and N-N DB geometries are predicted to form in an exothermic and spontaneous scheme. Cohesive energy of hexagonal GaN monolayer decreases when a DB is formed on its surface. Electronic structures for Ga-Ga DBs for 2×2, 3×3, 4×4 and 5×5 phases show spinpolarized and degenerate bands mainly contributed by p-orbitals of the atoms in impurity zone. Degenarated bands are not observed for N-N dumbbell for HDP, TDP, 2×2 and 3×3 phases. Upon DB formation, semiconductor GaN monolayer become spin-polarized semiconductor with varying band gap, where this functionalization allows electronic structure to be tuned substantionally. This would be highly desired for nanoscale electronic and optical devices. These Ga-Ga and N-N DB geometries may also be used for the synthesis of layered GaN structures.
Yüksek yoğunluklu CMUT iletim dizilerinin ışın yönlendirme uygulamarı için tasarımı, üretimi ve kullanımı
Several studies have reported airborne ultrasound transmission systems focused on achieving beamforming. However, beam steering and beamforming for capacitive micromachined ultrasonic transducers (CMUTs) at high intensity remains to be accomplished. CMUTs, like other ultrasonic transducers, incorporate a loss mechanism to obtain a wide bandwidth. They are restricted to a limited amount of plate swing due to the gap between the radiating plate and the bottom electrode, along with a high dc bias operation. CMUTs can be designed to produce high-intensity ultrasound by employing an unbiased operation. This mode of operation allows the plate to swing the entire gap without collapsing, thus enabling higher intensity. In this study, we use an equivalent circuit-based model to design unbiased CMUT arrays driven at half the mechanical frequency. This model is cross verified using finite element analysis (FEA). CMUT arrays are produced in multiple configurations using a customized microfabrication process that involves anodic wafer bonding, a single lithographic mask, and a shadow mask. We use impedance measurements to characterize the microfabricated devices. We experimentally obtained the highest reported intensity of 144 dB // 20uPa referred to the array surface using a microfabricated 2×2 CMUT array driven at resonance in a pulsed configuration. This array is also capable of beam steering and beamforming at a high intensity such that it can steer the entire half-space. The beam obtained from the array is in excellent agreement with the theoretical predictions. The amplitude and phase compensation for the devices remain constant that makes these arrays attractive for applications involving park assist, gesture recognition, and tactile displays.
Böbrek hastalıklarının takibinde kullanılabilir çok katmanlı tüm hücre sensörleri ile oluşturulmuş biyoteşhis cihazları
Development of accurate, inexpensive and fast-screening devices has been a big vacancy in the field of medical diagnostics. Close monitoring and diagnosis of various diseases are generally conducted by typical analytical techniques which require intensive efforts and qualified personnel. Therefore, there is an urgent need for more convenient and reliable alternatives that are highly specific, cost-efficient and rapid. One of the approaches in solving this problem is using naturally-derived proteins and nucleic acid molecules that can respond to various types of metabolites. Synthetic biology utilizes these components to assemble biological systems that can probe and control metabolic state of a host. In this context, biosensors can be considered highly specific, cost-effective and can be implemented in point-of-care bioanalytical tools for effective healthcare. Here, we have developed biosensors that are responsive to medically relevant biomarkers namely; urea and uric acid. Furthermore, a multi-input version that can sense and respond to both biomarkers simultenously and another multiplexed biosensor that can mimic the AND-logic were developed. Biosensors were designed to respond to their respective target analyte presence through an increase in the fluorescence intensity which can be measured with spectrophotometric devices. To do so, native promoter and transcription factors from different organisms were assembled inside a gene circuit to express a fluorescent protein in the presence of the respective biomarker. For urea biosensor, UreR transcriptional activator and the complete intergenic region inside the urease operon of the organism Proteus mirabilis were utilized. The system was optimized to have the desired dose- response curve using post trancriptional regulation elements and protein engineering. For the uric acid biosensor, transcriptional repressor HucR and the transcription factor binding site inside the uricase operon from the organism Deinococcus radiodurans were assembled in a gene circuit as well as a Uric Acid Transporter (UACT). Using promoter engineering and copy number modifications the response curve of the system was optimized. Next, biological components of the biomarkers were assembled in a multiplexed system to respond both molecules simultenously. Furthermore, a logic gate operating system was developed using promoter engineering that performs AND-logic to be implemented in a medically relevant algorithm A framework for stabilization of biosensors on low-cost portable paper discs through biofilm-cellulose interactions, and entrapment of whole-cell biosensors inside biocompatible, biodegradable and mechanically strong gelatin beads was provided for remote detection of the pathological biomarkers. Finally, the robustness of the developed whole cell biosensors was tested with human clinical samples.
Mikrobiyal amiloitlerin fonksiyonel biyomalzeme olarak kullanılması
Amyloids are fibrillar aggregations of proteins, dominated by β-sheets in the structure. They have high mechanical strength and rigidity that provides resistance to physical and chemical stress. In addition, amyloids can be easily functionalized with peptide groups for desired applications. These properties make them suitable candidates for biomaterial applications. Binding behavior of curli based amyloids on medically relevant surfaces are critical for their utilization controllable biomaterials. Furthermore, functionalization tor curli fibers too enhance their binding kinetics to surfaces and to organisms may hold great potentials for their desired applications as biomaterials. In this thesis, we characterized the binding kinetics of CsgA and CsgB curli proteins on silica, gold and hydroxyapatite surfaces to precisely control their surface adhesion. We showed that according to the physicochemical properties of surfaces, CsgA and CsgB displayed different binding behavior. Second, we hypothesized that glycosylation could enhance surface adhesiveness of curli fibers. For this purpose, TasA protein is engineered to obtain a glycosylation site and depicted that glycosylation increased adhesiveness of TasA fibers to gold surfaces. Finally, we functionalized CsgA curli fibers with RGD peptide to increase adhesiveness to living cells. Our results demonstrated that RGD peptide addition cause a significant increase in the number of cells adhered onto coated surfaces. In conclusion, amyloid proteins can serve as superior biomaterials with desired functionalities. Physicochemical properties of surfaces and proteins can have essential impacts on their interaction. In order to diversify those properties, amyloid fibers can be easily functionalized for specific purposes such as improved surface and cell adhesion. Functionalization with different peptide groups can extend their application capacity as superior biomaterials.