Graduate Program in Materials Science and Nanotechnology - Ph.D. / Sc.D.

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https://hdl.handle.net/11693/13950

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Colloidal synthetic pathways of atomically-flat complex nanocrystal heterostructures
(Bilkent University, 2024-01) Shabani, Farzan
Colloidal semiconductor nanocrystals (NCs) constitute one of the most important branches of nanoscience, with an increasingly high research interest, culminating with a Nobel Prize most recently. The nanometric size of these NCs allows for size-dependent optical properties, which provides an extra tool besides the composition to fine-tune these properties. Recent advancements in NC synthesis have been enabling important developments in the design and engineering of different shapes, compositions, and heterostructures of NCs. Accompanied by a deeper physical understanding and more sophisticated fabrication techniques, the NCs are now being integrated into many of the optoelectronic devices and are of prime importance for the next-generation optoelectronics. Despite all the progress, however, the full potential and synthesis dynamics of the NCs still need further investigation. Here, we addressed specifically four key aspects of the semiconductor NCs: shape engineering, electronic heterostructures, doping, and surface modification. In this thesis research, the synthesis dynamics, especially nucleation, growth and diffusion, were investigated in depth for different synthetic routes and conditions, and some of the important challenges were resolved. With the scarce number of proper emitters at longer wavelengths, in this thesis, a complex and thick heterostructure based on group II-VI nanoplatelets (NPLs) with relaxed quantum confinement was developed. The multi-shell design of the proposed NPLs helps overcome the unfavorable growth in the thickness direction, which, together with the cation dissolution/recrystallization and cation reorganization at high temperatures, relaxes the strain between the domains. The final NPLs, emitting in the deep-red region close to the bulk bandgap of CdSe, were used as an active layer in a light-emitting diode (LED) device and exhibited an exceptionally high external quantum efficiency (EQE) of 6.8% at electroluminescence peak wavelength of 701 nm, one of the best reported for colloids in this spectral range in the literature. Additionally, a novel heterostructure of multi-crown NPLs was designed and demonstrated, where several direct and indirect recombination pathways give rise to photoluminescence with both type-I and type-II characteristics. The design of these NPLs, especially the size of the domains, was shown to significantly impact the final optical properties that can activate/deactivate the recombination channels alongside the temperature. These multi-crown type-II NPLs exhibit an extremely high two-photon absorption cross-section with the highest value of 12.9 × 106 GM and low dark-bright exciton splitting energy critical for optoelectronic applications, including photodetectors, bioimaging and quantum devices. Next, we showed silver doping dynamics of core/shell NPLs, which previously proved challenging due to the self-purification after the shell growth. Here, the composition of the shell was shown to be an important factor in the destruction mechanism of the NPLs in the irreversible doping regime at high doping temperatures. The Ag:CdSe/CdZnS core/shell NPLs exhibit only dopant emission with superior paramagnetic properties compared to CdS-shelled NPLs thanks to better lattice preservation and higher dopant content. At last, a surface modification method was suggested and demonstrated for group I-III-VI NCs to enhance their electronic properties. Replacing the long-chain organic ligands with a S2- layer, injection of a negative charge and passivation of donor sites changed the behavior of the field-effect transistors (FETs) based on these NCs from p-type to n-type with more than a 105-fold enhancement in the carrier mobility. This method allowed fine-tuning of the optical properties of the NCs by the diffusion of the cations and shell formation. The findings of this thesis shine light on some of the important challenges in the field of semiconductor NCs while drawing a guideline for future research on the synthetic routes and optoelectronic properties. The thesis paves the way for future device integration of the developed NCs to fully realize their potential, while the demonstration of the more elaborated properties, including nonlinear absorption, paramagnetism and dark-bright exciton splitting, encourages further fundamental studies focusing on the physics of the semiconductor NCs.
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Biotechnological drug platforms
(Bilkent University, 2023-11) Ahan, Recep Erdem
Biopharmaceuticals, also known as biotechnological drugs, have revolutionized the treatment of many diseases by providing access to new mechanisms of action that can target the underlying biological processes behind the diseases. Technological advancement in biological sciences opens new paths to uncover new biopharmaceutical modalities in nature as well as to augment the existing modalities new functions. The implementation of engineering principles i.e., synthetic biology approaches have been transforming biopharmaceutical research wherein “smart” therapeutics are developed and deployed for treatment of previously intractable diseases. However, there are still unmet clinical needs that require novel and advanced biopharmaceuticals. In this thesis, I explored different biopharmaceuticals to characterize and/or advance their capabilities for diverse indications. Firstly, we have developed a prophylactic agent from the lectin protein, griffithsin, as for ancestral and the emerged strains of SARS-CoV-2. Secondly, we have advanced genetic technologies to engineer the probiotic Escherichia coli (E. coli) strain, Nissle 1917 (EcN), for therapeutical purposes. We developed a stable recombinant DNA transfer system based on cryptic plasmids of EcN. Furthermore, a synthetic protein secretion system was envisioned and functionally validated in EcN to shuttle therapeutical proteins to diseases site. Finally, peptide tags for extracellular protein secretion as well as a cell surface protein display system were developed for Lachnospiraceae species which are parts of the healthy human gut microbiome. The technologies and methodologies described herein will pay the way for inventing and/or discovering novel biopharmaceuticals to treat current and future diseases.
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Prediction of new generation two-dimensional ternary structures and investigation of their fundamental properties
(Bilkent University, 2023-05) Varjovi, Mirali Jahangirzadeh
Consecutive to the isolation of graphene and uncovering its extraordinary properties, the dynasty of two-dimensional (2D) materials has expanded rapidly. A realization of every new member suggests novel features, holding the promise to be used in current and prospective nanodevices. In parallel with the attempts on exploring new 2D systems, the formation of ternary configurations has been suggested as an alternative approach to tailor the inherent properties of the already existing 2D structures. In accordance with recent advancements in ternary 2D systems, in this dissertation, we design and investigate the 2D systems which possess three types of elements in their crystal structure. In this regard, we design Janus Al2XX′ (X/X′: O, S, Se, Te) crystals, 1H, 1T, and 1T′ phases of Janus WXO (X = S, Se, and Te) monolayers and Janus BiXY (X= S, Se, Te, and Y = F, Cl, Br, I ) nanosheets and investigate their structural, vibrational, elastic, piezoelectric, and electronic properties by first-principle methods. In addition, inspired by the synthesis of penta-Si nanoribbons, advancements in 2D pentagonal systems, and recent developments on ternary structures, we propose and investigate a new ternary pentagon-based 2D monolayer, namely penta-BNSi. We study the mechanical, electronic, piezoelectric, photocatalytic, and optical properties of penta-BNSi crystal and reveal its suitability to be used in optoelectronics and photocatalytic applications. Then, we focused our attention on new family of MA2Z4 monolayers. Based on this motivation, we perform a comprehensive study on physical properties of MSi2Z4 (M: Pd and Pt, Z: N and P) monolayers and suggested novel single layer of InSiN2 (In2Si2N4). For this purpose, in both studies, the ground state configurations of the designed materials are determined, and then the dynamical and thermal stability of these nanosheets are investigated using phonon spectrum analysis and ab initio molecular dynamic (AIMD) simulations, respectively. Next, each structure’s Raman and infrared (IR) spectrum are analyzed, and the corresponding atomic displacements of the optical phonon modes are presented. Then, the mechanical properties are studied in terms of in-plane stiffness and Poisson’s ratio. The electronic band structures are computed in the electronic properties section, and the corresponding energy band gaps are reported. For MSi2Z4 (M: Pd and Pt, Z: N and P) monolayers, the optical response is examined via calculation of the complex dielectric function by taking many-body interactions into account. In the final study, the effect of an external biaxial strain on the electronic and vibrational properties of the InSiN2 nanosheet is investigated, and the variation of the obtained properties under strain is illustrated. As a result of a thorough theoretical study focusing on ternary 2D materials, it can be said that the examined crystals are stable systems with potential applications in a wide range of nanoelectronics and nanomechanical devices.
Open Access
The investigation of advanced thermoplastic composite materials in aerospace applications
(Bilkent University, 2023-05) Yavuz, Zelal
The development of load-carrier reinforced composites is crucial in terms of a wide range of applications, such as aerospace, automotive, sports industry and so on. When these fields are taken into consideration, reducing the excessive weight of structural materials without any sacrifice in the performance is required. Thus, using reinforcement materials (e.g. carbon fibers) for polymeric matrices in composites is the most convenient way to follow. In this study, carbon fiber (CF) was used as a reinforcement material for thermoplastic based composites. Since bare CFs are too fragile to process they must be coated / sized such that the brittleness of CFs can be avoided during industrial applications. Therefore, sizing of carbon fibers is crucial for guiding them into service by protecting the CF’s surface. Yet, the traditional sizing agent (i.e. epoxy) is not suitable for handling continuous CF reinforced thermoplastic composites (CFRTPs) with high processing temperatures above 300 ℃. In this study a novel sizing agent was developed for this purpose. The effects of this sizing on the CFs’ physicochemical as well as surface properties were investigated. As a result, the impact on fiber-matrix interphase behavior can be analyzed. Moreover, the main problem for thermoplastic based composites which is the delamination between the reinforced fiber and thermoplastic matrix can be solved throughout the development of novel coating material so that inert carbon fibers can be made compatible with the matrix. In this thesis, the activation of carbon fiber’s surface, then providing a functional sizing agent and method in order to expel the present voids because of incompatibility between CF and thermoplastic matrix (i.e. Polyetherether ketone) were carried out by enhancing the adhesion. Hence, the wettability of CF by polyetherether ketone (PEEK) matrix was enhanced by altering the surface free energy of CF resulting in optimized adhesion. Thus, the delamination problem in thermoplastic based composites was solved throughout the sizing of CFs. The first part of this work consists of the elimination of current epoxy coating on the aerospace grade commercial carbon fibers. Then, the application of surface activation method was performed by acidic modification to make CFs ready for sizing process. The formation of functional groups (-COOH, -OH) on CF’s surface was achieved after degrading of present epoxy coating throughout CFs. As a result, the developed sizing agents could be binded easily onto CF’s activated surface through the hydrogen bonding. In the second part, four different polymeric sizing agents were prepared by taking the chemical compatibility with the matrix into consideration. The sizing process was performed via dip-coating method for the surface-activated CFs. The chemical and physical analyses for neat and treated CFs were carried out via microscopic and spectroscopic techniques. As a result of sizing process, the enhanced compatibility between the matrix and reinforcement material was proved by the Contact Angle Analysis and surface free energy calculations according to Young’s equation.
Open Access
Tuning the resonances of high Q-factor whispering gallery mode resonators for optoelectronic applications
(Bilkent University, 2022-07) Hüseyinoğlu, Ersin
Optical resonators allow highly efficient light-matter interaction; therefore, they are promising tools for optoelectronics and photonics. Especially optical resonators with high Q-factors such as toroidal resonators can be instrumentalized to develop efficient light sources, modulators, converters, and sensitive detectors. They are already being used for photonics research; however, some significant obstacles hinder their mass utilization in the industry. One of those obstacles is the current limitations of the fabrication method used to produce toroidal resonators. Due to the method used to achieve surface tension-induced microresonators (STIM), their fabrication is time-consuming. A new approach was presented to mass-produce STIMs. Instead of a fixed position laser, a raster scan laser was used to reflow the microresonators with different geometry types to overcome the mass-fabrication limitations. As a result, high-Q-factor (10^6) toroidal resonators were fabricated. Reflowing of elliptical and racetrack resonators were also demonstrated. Another problem that hinders the utilization of toroidal resonators is their high susceptibility to any errors originating from the fabrication process. Any deviation from the designed parameters leads to resonators with different resonant modes. A method for post-production tuning resonant mode of chalcogenide coated resonator was demonstrated. By using a thin Ge2Sb2Te5 layer coated silica toroidal resonator, 0.01 nm and 0.02 nm permanent mode shifts were achieved from 5 nm thick coated and 10 nm thick coated resonators, respectively.
Open Access
Color generation and enhancement using large-scale compatible metamaterial design architectures
(Bilkent University, 2022-01) Köşger, Ali Cahit
Metamaterials are a type of artificial matt that can impose exotic functionalities beyond natural materials. These specifically designed sub-wavelength structures acquire these functionalities from their collective geometric arrangement rather than their individual single-unit properties. As a result, metamaterials have shown promising applications, including negative refraction, artificial magnetism, asymmetric transmission, lasing, and cloak of invisibility. Among all these applications, the concept of color generation and enhancement using metamaterial designs have attracted much attention in recent years. We can achieve color generation from two primary sources: i) filtering white light, and ii) generating light from emitting materials such as quantum dots. In color generation using white light, a metamaterial design reflects or transmits a narrow portion of the incident spectrum. Thus, the design acts as a color filter. However, the source is already a narrowband color light in the second category. Thus metamaterials merely amplify the color intensity rather than manipulate its spectral response. In this thesis, metamaterial structures are designed, fabricated, and characterized in both categories mentioned above; The content of this thesis consists of two parts; i) In the first part, we generated additive red-green-blue (RGB) colors in reflectance mode with near-unity amplitude. For this purpose, we designed a multilayer structure made of metal-insulator-metal-semiconductor-insulator (MIMSI) stacks to achieve >0.9 reflection peaks with full-width-at-half-maximum (FWHM) values <0.3λpeak. The proposed design also shows near-zero reflection in off-resonance spectral ranges, which, in turn, leads to high color purity. Finally, we fabricated the optimized designs and verified the simulation and theoretical results with characterization findings. This work demonstrates the potential of multilayer tandem cavity designs in realizing lithography-free large-scale compatible functional optical coatings. ii) In the second part, we utilized a large-scale compatible plasmonic nanocavity design platform to achieve almost an order of magnitude photoluminescence enhancement from light-emitting quantum dots. The proposed design is multi-sized/multi-spacing gold (Au) nano units that are uniformly wrapped with thin aluminum oxide (Al2O3) layer as a foreign host to form a metal-insulator-semiconductor (MIS) cavity, as we coated them with semiconductor quantum dots (QDs). Our numerical and experimental data demonstrate that, in an optimal insulator layer thickness, the simultaneous formation of broadband Fabry-Perot (FP) resonances and plasmonic hot spots leads to enhanced light absorption within the QD unit. This improvement in absorption response leads to the PL enhancement of QDs. This work demonstrates the potential and effectiveness of a host comprised of random plasmonic nanocavities in the realization of lithography-free efficient emitters. Overall, this thesis presents an alternative perspective on applying large-scale compatible metamaterials in color generation. Furthermore, the proposed designs and routes can be extended toward other functional photoelectronic designs, where high performances can be acquired in scaleable architectures.
Open Access
Development of high-beam quality high power Ytterbium-doped fiber lasers
(Bilkent University, 2022-01) Midilli, Yakup
High power fiber laser (HPFL) systems have drawn considerable interest for the last decades in health, industry, and especially defense applications due to their compactness, robustness, and high directionality. In this respect, the defense industry is currently in high demand for HPFL systems in the naval, air force, and ground operations. As an example, they have been implemented to the battleship, armored vehicles, and most currently to the drones. Outstanding features of these systems allow us to utilize them in various applications; however, this great demand brings some shortcomings. For example, power scaling of highpower fiber lasers has been impeded by non-linear interactions such as Stimulated Raman Scattering (SRS) and Transverse Mode instability (TMI). Regarding these non-linear interactions, I have built high-power fiber laser oscillators and amplifier systems based on both commercial and homemade selffabricated Ytterbium (Yb)-doped large mode area active (LMA) fibers. Amplifier systems have been built based on the Master Oscillator Power Amplifier (MOPA) configuration, and the average power reaches up to 1 kW power level. Besides, the fiber oscillator system has been built with a power level up to 2 kW power level and M2 value of 1.2, the beam quality parameter of the fiber laser system. To understand and investigate the TMI effect on the fiber laser system and the fiber itself, I have intended to observe the intensity change of the probe lasers and the color center formation inside a homemade active fiber in the presence of TMI. Then, I have rebuilt the system to eliminate the TMI effect and repeated the same experiments to ensure that the TMI effect was responsible for the difference. For that purpose, I have installed a fiber laser system whose fiber has been coiled in a large bending diameter to ensure the existence of the TMI effect. I have utilized two different probe lasers with 645 nm and 520 nm central wavelengths, respectively. I have coupled these probe lasers to the fiber laser system via freespace arrangements. Afterward, I have repeated the same experiment only with the 520 nm probe laser ensuring the absence of the TMI effect by rebuilding the laser structure. Finally, I have taken data about the intensity change of the probe lasers for both cases and compared them. Having benefited from the experience of these studies, to suppress the SRS and TMI, I have fabricated a new type of generation Yb-doped LMA active fiber having an ultra-low numerical aperture (NA) around 0.034. Then I have built a monolithic MOPA system based on this fiber with a 1 m bending diameter. In addition, I have obtained 1 kW maximum power with a diffraction-limited beam quality with an M2 value of 1.16. Additionally, I have studied the side-pump combining technique, which is one of the mitigation methods for TMI. It allows us to pump the active fiber from both sides, thus decreasing the thermal load on fiber. Finally, I have studied the side pump combiner on both homemade self-fabricated Photonic Crystal Fiber (PCF) and ultra-low NA active fiber in a (1 + 1) x 1 pumping configuration with 95% and 89% pump coupling e ciencies, respectively.
Open Access
Survival analysis and its applications in identifying genes, signatures, and pathways in human cancers
(Bilkent University, 2021-09) Özhan, Ayşe
Cancer literature makes use of survival analyses focused on gene expression based on univariable or multivariable regression. However, there is still a need to understand whether a) incorporating exon or isoform information on expression would improve estimation of survival in cancer patients; and b) applying multivariable regression to gene sets would allow to obtain cancer-specific independent gene signatures in cancer. Differential usage of individual exons, as well as transcripts, are phenomena common to cancerous tissue when compared to normal tissue. The glioblastoma, GBM; liver cancer LIHC; stomach adenocarcinoma, STAD; and breast carcinoma, BRCA datasets from The Cancer Genome Atlas (TCGA) were investigated to identify individual exons and transcripts with transcriptome-wide impact and significance on survival. Aggregation analyses of exons revealed the important genes for survival in each dataset, including GNA12 in STAD, AKAP13 in LIHC and RBMXL1 and CARS1 in BRCA. GSEA was applied on gene sets formed from the exon-based analysis, revealing distinct enrichment profiles for each dataset as well as overlaps for certain GO terms and KEGG pathways. In the second focus of this thesis, multivariable analyses on gene sets whose expressions were obtained from UCSC Xena were used to create two Shiny applications: one for dataset-specific analyses and one for analyses across TCGA-PANCAN. The dataset specific SmulTCan application incorporates Cox regression analyses with expressions of input genes of the user’s choice. The SmulTCan application contains additional model validation, best subset selection and prognostic analyses. The ClusterHR application performs clustering analyses with Cox regression results, while it can also be used for bicluster identification and comparison. The axon-guidance ligand-receptor gene sets Slit-Robo, netrins-receptors and Semas-receptors were used for demonstrating the apps. Several hazard ratio signatures and best subsets that can differentiate between prognostic outcomes have been identified from the input gene sets, as well as ligand-receptor pairs with prognostic significance.
Open Access
Design of multifunctional prussian blue analogues for solar driven water oxidation
(Bilkent University, 2021-07) Ghobadi, Türkan Gamze Ulusoy
The development of earth-abundant, robust, and low-cost photoanodes for water oxidation is one of the most critical steps in ‘artificial leaf’. A promising approach in this field is to build dye-sensitized photoanodes by coupling a molecular photosensitizer (PS) with a water oxidation catalyst (WOC) on a proper semiconductor (SC) for efficient charge separation. All dye-sensitized photoanodes reported in the literature consist of either a ruthenium photosensitizer, a ruthenium water oxidation catalyst, or both. We aim to overcome this critical challenge by developing a new family of organic- or iron-based donor-acceptor chromophores incorporated in a Prussian blue (PB) structure, which are coated on proper semiconductors. Our studies within this context could be divided into three sections: (i) PB based photocatalytic water oxidation: In this work-package, an entirely precious metal-free chromophore-donor-water oxidation catalyst triad system is developed. The synthesis involves the coordination of a porphyrin derivative to a bridging Fe(CN)5 group, which is then reacted with cobalt ions to prepare a covalently linked chromophore-Prussian blue analogue (CoFe(CN)5–Ligand) assembly. Light-driven water oxidation studies in the presence of an electron scavenger indicate that the triad is active and maintains a steady activity for at least 3 hours. Transient absorption experiments and computational studies reveal that the Fe(CN)5 group is more than just a linker. It takes part in electron donation and co-operates with porphyrin in the charge separation process. (ii) PB based photoelectrochemical water oxidation: Here, we move one step forward and design a ruthenium-free water oxidation photoanode by the sensitization of titanium dioxide (TiO2) nanowires with a PB-organic chromophore structure. A phenazine-based organic group, Janus Green B (JG), is chosen as the chromophore since it has a broad absorption response in the visible and near-infrared ranges. The resulting multifunctional PB modified TiO2 electrode demonstrates a low-cost and easy-to-construct photoanode, which exhibits a remarkable excited-state lifetime in the order of nanoseconds and an extended light absorption capacity of up to 500 nm. Moreover, the photoanode retains its structural integrity and photoelectrochemical activity for at least 2 hours. Despite all the above-mentioned improvements, the performance of the cell, [CoFe–JG]/TiO2, is relatively poor due to improper band energy alignment between the chromophore and the semiconductor. In a follow-up study, we tune the chromophore and the semiconductor to achieve a proper band energy alignment, and thus, to improve the performance. Another phenazine-based molecule, Safranin O (SF), is utilized as the organic photosensitizer. Moreover, a visible-light absorbing semiconductor, WO3, is used to utilize the solar spectrum completely. [CoFe–SF]/WO3 exhibits a record photocurrent density of 1.3 mA/cm2 at 1.23 VRHE, demonstrating that proper modification of components in PB based dye-sensitized photoanodes could pave the way for the development of high-performance water splitting cells. (iii) Iron chromophore based photoelectrochemical water oxidation: In this section, the iron site that has been previously utilized as a relay is promoted to an iron chromophore. Five cyanide ligands are coordinated to the iron site to destabilize the metal-centered states. At the same time, an electron-deficient cationic pyridinium group occupies the remaining coordination sphere of the octahedral iron site to facilitate the metal-to-ligand charge transfer (MLCT) process. This iron complex is coated initially on TiO2 nanowires and then reacted with cobalt ions to produce a CoFe PB (CoFe(CN)5-L) layer on the electrode surface. In this photoanode, the excited-state lifetime of the iron chromophore exceeds 1 ns, which demonstrates the first example of an iron-sensitized water oxidation cell in the literature. Overall, this thesis presents an alternative perspective to realize high performance, low-cost, stable, and robust dye-sensitized water oxidation systems. The impact of the acquired knowledge in this thesis is also discussed to define the current status, challenges, and future of PB based water oxidation systems.
Open Access
Real time optical observation of the synthesis of novel 2D materials and investigation of their fundamental properties
(Bilkent University, 2021-03) Rasouli, Hamid Reza
Two-dimensional transition metal dichalcogenide (2D TMDC) with superb phys-ical and chemical properties, used as the active material for various devices. The on-going primary focus is their reliable high-throughput synthesis using processes compatible with the current semiconductor technology. At present, among the common approaches, chemical vapor deposition (CVD) has been considered as the most promising method for preparing large-area high-quality 2D materials. However, the lack of in-situ information during the growth in conventional CVD systems, makes it impractical to realize high-temperature phenomena. In this thesis, we developed a novel CVD chamber that allows real time optical obser-vation and control of the crystal growth. Using this new CVD method, which we call real time optical-CVD, RTO-CVD in short, we elaborated the involved mechanisms in salt-assisted synthesis of TMDCs and their vertical/lateral het-erostructures. Through direct visualization of WSe2 monolayer growth, we iden-tiﬁed that both vapour-solid-solid and vapour-liquid-solid growth routes are in an interplay. Then, we focused our attention to synthesize novel 2D materials such as V2O3 and K-MnO2 nanosheets. We succeeded synthesis route in favor of high-quality single-crystalline V2O3 nanoplates whose 2D characteristic allows us to study their peculiar electrical and physical properties such as metal-insulator transition (MIT) and supercritical state. The electrical properties of both as-grown and transferred V2O3 crystals were investigated with respect to the V2O3 phase-stability diagram. We observed emergence of a novel crystal structure upon electron beam heating in selected area electron diﬀraction (SAED) experi-ments and correlated it to the supercritical state by means of high-temperature Raman spectroscopy. Finally, we introduced large-area ultra-thin layered MnO2 crystals, spontaneously intercalated by potassium ions during the synthesis. The charge transport in 2D K-MnO2 devices was shown to be dominated by the in-plane ionic conductivity through the motion of hydrated K ions in the interlayer space. The K-MnO2 crystals exhibited reversible layered-to-spinel phase tran-sition accompanied by an optical contrast change based on the electrical and optical modulation of the potassium and the interlayer water concentration. We used the electric-ﬁeld driven ionic motion in K-MnO2 devices to demonstrate the memristive properties and elucidated the resistance-switching mechanisms via real-time analyses upon the measurements. K-MnO2 memristors were artiﬁcially able to emulate neuromorphic synapse-like behaviors, namely short and long-term potentiation/depression as well as ionic coupling eﬀects.
Open Access
Microbial amyloids as functional biomaterials
(Bilkent University, 2021-01) Kehribar, Ebru Şahin
Amyloids are fibrillar aggregations of proteins, dominated by β-sheets in the structure. Although amyloids are historically associated with disorders, they emerged as outstanding biomaterials due to their high mechanical strength and rigidity that provides resistance to physical and chemical stress. Also, amyloids can easily be functionalized with peptide groups using genetic engineering approaches. Ease of functionalization in addition to aforementioned properties makes amyloid fibers excellent candidates for biomaterials with desired characteristics. In this thesis, we focused on recombinant production, characterization and functionalization of several amyloid proteins from different microorganisms. Binding behavior of amyloid fibrils on medically relevant surfaces are critical for controlling the coating characteristics and desired surface properties of biomaterials. For this reason, we firstly characterized the binding kinetics of CsgA and CsgB curli proteins on silica, gold and hydroxyapatite surfaces to precisely control their surface adhesion. According to the physicochemical properties of surfaces, CsgA, CsgB and their mixture displayed different binding behavior. Furthermore, functionalization of amyloid fibers to enhance their binding kinetics to surfaces and to organisms may hold great potentials for biomaterial applications. From this perspective, we hypothesized that glycosylation could enhance surface adhesiveness of curli fibers. For this purpose, TasA protein is engineered to obtain a glycosylation site and TasA fibers depicted an increased adhesiveness to gold surfaces upon glycosylation. Finally, we functionalized CsgA curli fibers with RGD peptide to increase adhesiveness to living cells. RGD peptide addition caused a significant increase in the adhesiveness of mammalian cells onto coated surfaces. In conclusion, amyloid proteins can serve as superior biomaterials with desired functions and characteristics. Physicochemical properties of surfaces and proteins can have essential impacts on their interaction. In order to diversify those properties, amyloid fibers can be functionalized for specific purposes such as improved surface and cell adhesion. Characterization of protein/surface interactions for amyloid proteins provides important clues for optimal biomaterial surface design and functionalization with different peptide groups can extend their application capacity as superior biomaterials.
Open Access
Design, fabrication and operation of a very high intensity CMUT transmit array for beam steering applications
(Bilkent University, 2020-12) Khan, Talha Masood
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 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.
Open Access
Functionalization of group V monolayers and their compounds: alloying, doping and surface modification
(Bilkent University, 2020-11) Kanlı, Muammer
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.
Open Access
Analysis of monodisperse microfluidic droplet generation and its biochemical applications
(Bilkent University, 2020-11) Kalantarifard, Ali
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.
Open Access
Optoelectronic and thermal properties of metallic transition metal dichalcogenides
(Bilkent University, 2020-11) Mehmood, Naveed
After the successful isolation of graphene monolayer from its bulky counterpart, there has been tremendous advancement in the field 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 findings, 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 finite 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(κ) as a fitting parameter via commercially available finite element method package(COMSOL). This way, thermal conductivity of the metallic TMDCs is calculated with very high accuracy and precision.
Open Access
Encapsulation of food additives and drugs by cyclodextrin functionalized electrospun nanofibers
(Bilkent University, 2020-06) Yıldız, Zehra İrem
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.
Open Access
Synthetic genetic circuits to monitor nanomaterial triggered toxicity
(Bilkent University, 2020-07) Saltepe, Behide
In the past decades, nanomaterial (NM) usage in various fields has been of great interest because of their unique properties that show tuneable optical and physical properties depending on their size. Yet, safety concerns of NMs on human or environment arise with increased NM usage. Thanks to their small size, NMs can easily penetrate through cellular barriers and their high surface-to-volume ratio makes them catalytically active creating stress on cells such as protein unfolding, DNA damage, ROS generation etc. Hence, biocompatibility assessment of NMs has been analyzed before their field application such as drug delivery and imaging which requiring human exposure. Yet, conventional biocompatibility tests fall short of providing a fast toxicity report. One aspect of the present thesis is to develop a living biosensor to report biocompatibility of NMs with the aim of providing fast feedback to engineer them with lower toxicity levels before applying on humans. For this purpose, heat shock response (HSR), which is the general stress indicator, was engineered utilizing synthetic biology approaches. Firstly, four highly expressed heat shock protein (HSP) promoters were selected among HSPs. In each construct, a reporter gene was placed under the control of these HSP promoters to track signal change upon stress (i.e., heat or NMs) exposure. However, initial results indicated that native HSPs are already active in cells to maintain cellular homeostasis. Moreover, they need to be engineered to create a proper stress sensor. Thus, these native HSP promoters were engineered with riboregulators and results indicated that these new designs eliminated unwanted background signals almost entirely. Yet, this approach also led to a decrease in expected sensor signal upon stress treatment. To increase the sensor signal, a positive feedback loop using bacterial communication, quorum sensing, method was constructed. HSR was integrated with QS circuit showed that signal level increased drastically. Yet, background signal also increased. Moreover, instead of using activation based HSR system as in Escherichia coli, repression based system was hypothesized to solve the problem. Thus, a repression based genetic circuit, inspired by the HSR mechanism of Mycobacterium tuberculosis, was constructed. These circuits could report the toxicity of quantum dots (QDs) in 1 hour. As a result, these NM toxicity sensors can provide quick reports, which can lower the demand for additional experiments with more complex organisms. As part of this study, a source detection circuit coupling HSR mechanism with metal induced transcription factors (TFs) has been constructed to report the source of the toxic compound. For this purpose, gold and cadmium were selected as model ions. In the engineered circuits, stress caused by metal ions activates expression of regulatory elements such as TFs of specific ions (GolS for gold and CadR and MerR(mut) for cadmium) and a site-specific recombinase. In the system, the recombinase inverts the promoter induced by TF-metal ion complex, and a reporter has been expressed based on the inducer showing the source of the stress as either gold or cadmium. Finally, a mammalian cellular toxicity sensor has been developed using similar approaches used in bacterial sensors. To begin with, two HSP families have been selected: HSP70 and α-Bcrystallin. Initial circuits were designed using promoter regions of both protein families to control the expression of a reporter, gfp. Both circuits were tested with heat and cadmium ions with varying concentrations and results showed that HSP70-based sensor had high background signal because of its active role in cellular homeostasis and protein folding in cells. Additionally, a slight increase was observed after heat treatment. Similar results were observed for α-Bcrystallin-based sensor; yet, these outcomes were not suitable for a desirable sensor requiring tight control. Thus, we decided to transfer the bacterial repression based toxicity sensor into mammalian cells. At the beginning, expression of the repressor, HspR, from M. tuberculosis was checked in HEK293T cell line and modified with nuclear localization signal (NLS) to localize the repressor in the nucleus. Further, a minimal promoter (SV40) controlling the expression of a reporter was engineered with single and double inverted repeats (IRs) for HspR binding. Then, HspR and engineered reporter circuits were co-trasfected to track signals at normal growth conditions and upon stress. Each circuit was tested with heat and cadmium treatment and results were showed repression of GFP expression by HspR at normal conditions, but no significant signal increase was observed upon stress. Hence, constructed mammalian circuits require more optimization to find optimum working conditions of sensors. To sum up, in this study, a powerful candidate to manufacture ordered gene circuits to detect nanomaterial-triggered toxicity has been demonstrated. Unlike previous studies utilizing HSR mechanism as stress biosensors, we re-purposed the HSR mechanism of both bacteria and mammalian cells with different engineering approaches (i.e., riboregulators, quorum sensing mechanism, promoter engineering). As a result, an easy-to-use, cheap and fast acting nanomaterial-triggered toxicity assessment tool has been developed. Also, initial principles of mammalian whole cell biosensor design for the same purpose have been indicated to expand the limited toxicity detection strategies utilizing mammalian cells. This study contributed for the detection of toxic NMs providing a feedback about the fate of these NMs so that one can engineer them to make biocompatible before field application.
Open Access
Development of viscoelastic particle migration for microfluidic flow cytometry applications
(Bilkent University, 2020-04) Serhatlıoğlu, Murat
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. 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 emonstrated 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.
Open Access
Microfluidic platforms for hemorheology and coagulation time analysis
(Bilkent University, 2020-01) Işıksaçan, Ziya
Blood is a non-Newtonian ﬂuid consisting of plasma and cells that uninterruptedly circulate the body. Erythrocytes are deformable anucleated discoid blood cells with a viscoelastic membrane, constituting around half of blood volume. Hemorheology investigates blood ﬂow characteristics determined by hemorheological properties comprising aggregation, sedimentation, and deformation of erythrocytes as well as blood/plasma viscoelasticity. These hemorheological properties are intricately interdependent. Hence, acquired or hereditary disorders aﬀecting one hemorheological property (malaria, diabetes, anemia) lead to alterations in other properties. Available techniques lack the ability to measure these properties all-at-once and in physiologically relevant conditions. Blood coagulation is as essential as a healthy blood ﬂow. This is a body defense mechanism involving the interplay of blood constituents for stable clot formation to stop bleeding. Sensitive and periodic measurement of coagulation time is critical for individuals who are under the risk of excessive bleeding or thrombus-originated vessel obstruction. Today, these conditions are responsible for 25 percent of all deaths worldwide. Unfortunately, the conventional practice for coagulation monitoring is ﬁxed-interval hospital visits by patients. In this thesis, we present novel microﬂuidic platforms and measurement methods for the analysis of hemorheological properties and coagulation time parameters. The assays are based on optical quantiﬁcation of erythrocyte dynamics inside miniaturized channels. The measurements require only 50 µl undiluted blood and are completed in less than 5 min. Firstly, we demonstrate optical measurement of erythrocyte aggregation and rapid measurement of erythrocyte sedimentation rate (ESR) using aggregation dynamics. Secondly, we present the results of clinical ESR tests performed in a local hospital and compare the performance of the developed platform with the conventional 1-hour test. Simultaneously obtained optical transmission signals and real-time microscopic observations of erythrocytes in custom-developed cartridges validate the proposed measurement principle. Thirdly, we present a method oﬀering a holistic approach to blood ﬂow characterization. The method enables simultaneous analysis of multiple hemorheological properties by optically investigating collective erythrocyte dynamics, primarily deformation, in a channel during unique damped oscillatory sample motion. We create a ﬂuidic environment mimicking in vivo ﬂow: conﬁned, directional, and pulsatile movement of blood at ﬂow rates and hematocrit comparable to physiological levels. Fourthly, we present a method for blood coagulation time measurement by optical quantiﬁcation of erythrocyte aggregation. We demonstrate the fundamental relationship between aggregation and coagulation. Finally, we present an alternative, entirely disposable microﬂuidic platform for hemorheology and coagulation time analysis based on migration analysis of blood sample in microﬂuidic channels. Overall, the microﬂuidic platforms and measurement methods presented here will potentially initiate routine hemorheological and coagulation time analysis even in resource-poor setting.
Open Access
Biomineralization with engineered cellular systems
(Bilkent University, 2019-08) Ergül, Elif
Hydroxyapatite (HAP) is the final product of bone biomineralization process and HAP formation is controlled by proteins, enzymes and small molecules secreted to extracellular matrix (ECM). Among these molecules, alkaline phosphatase (ALP) leads formation of HAP crystals and noncollagenous proteins control crystal nucleation and growth, and inhibit crystal formation. Osteocalcin (OCN) and osteopontin (OPN), are the most abundant noncollagenous proteins in ECM, which controls mineralization events. In this study, effect of OCN and OPN on HAP crystal formation was studied in order to achieve controlled crystal growth. In vitro biomineralization assays were conducted to understand the effect of OCN and OPN on the crystal structure of as formed minerals. While OCN decreases crystal growth rate and inhibit mineralization, which leads to more uniform crystal formation, OPN provides faster mineral formation with reduced Ca/P ratio. Moreover, a mammalian engineered cell line was constructed to achieve expression of bone extracellular matrix (ECM) proteins. For this purpose, genetic cassettes were produced to express OCN and OPN proteins, which are the most common non-collagen proteins that control bone mineral formation. By this way, production of bone type minerals with controlled size, shape and Ca/P ratio can be possible. Our system provides a truly biomimetic approach to HAP formation compared to chemical synthesis methods in literature. We believe our current findings will lead to innovative approaches for bone biomineralization in regenerative medicine and bone tissue engineering.