LEE- Nano Bilim ve Nano Mühendislik-Yüksek Lisans
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Yazar "Alptürk, Onur" ile LEE- Nano Bilim ve Nano Mühendislik-Yüksek Lisans'a göz atma
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ÖgeDesign and simulation of a microfluidic biochip for optic detection with derivatized microbeads and the biochemistry of learning(Fen Bilimleri Enstitüsü, 2020) Tüysüz, Tuğçe ; Alptürk, Onur ; Uludağ, Yıldız ; 630291 ; Nano Bilim ve Nano MühendislikMicrofluidic systems are an important technology suitable for a wide range of applications due to their rapid response capabilities, low cost and, small amounts of sample need. Microfluidics tries to overcome difficulties in conventional assays in medical diagnosis. The combination of biosensors and microfluidic chips increases the analytical capability to extend the scope of possible applications. In this thesis, two types of microfluidic modeling were designed for biomedical applications. The first design is a bead derivatized sensor in a microfluidic chip to detect biomarkers. The second model is designed to observe the effect of α-syn protein which constitutes the communication of two nerve cells through channels in the microfluidic system and the long term potentiation. In Project 1, Integrated affinity sensors within microfluidic platforms show great interest in life environmental and science analytical science applications. They are generally placed in the base of a fluidic flow channel on which an analyte solution is passed. The analyte detection on the sensor depends on the event of a recognition-binding, most generally antigen-antibody, for which the recognition molecules are attached to the surface of the sensor for the analyte. The analyte -recognition molecule complex is detected on the sensor. The integration of bead-based immunoaffinity assays in microfluidic chips has recently become an area of interest for many researchers. Integrated affinity sensors inside of the microfluidic structures have many advantages which are low-cost, rapid, highly specific detection and sensitivity. In this study, the microfluidic system has been designed with different substrate patterns in the continuous flow of phosphate-buffered saline (PBS), and microbeads were examined. Functionalized microbeads have been used as biomolecules to enhance the affinity of biomarkers and for high sensitivity. Microchannel was patterned with square pyramid well array, conic well array, triangle pyramid array, and the each microbeads made of polystyrene were placed into the each microwell; PS beads were simulated with different flow rates. Initially, PBS was utilized to simulate blood serum, and PS nanoparticles, functionalized and fluorescently labeled nanoparticles that allow detection of biomarkers, were simulated for examination by fluorescence microscopy. As a result of three different geometric well chip patterns and three different bead size simulations, it was determined that the shape of the well should be conical and the bead size should be 150 µm. The lowest cross-section flow rate of the fluid sent from the inlet of the channel with a flow rate of 300 µl was determined in conical design. This indicates that there will be more interaction with the surface compared to other patterned arrays. In Project 2, The purpose of this project is to create a biosynthetic neuron-on-a-chip to reproduce the activity of neuronal function. Neurons are the main important units of the nervous system and brain. The target of neurons is to receive sensory input from the outside world and send motor commands to the muscles. They are also responsible for converting and transmitting electrical signals in every step that takes place in this cycle. Neurons communicate with electrochemical signals. Therefore, electrical and chemical events must occur together for the communication of two neuron cells. It transmits a neuron signal through the axons to the dendrites of other neurons to which it connects via the axons called synapses. Long Term Potentialization is a process in which synaptic connections between neurons are strengthened by frequent activation. LTP is thought to change the brain in response to experience, thereby providing a mechanism underlying learning and memory. In the process of learning, nerve cells, the basic computing units of any nervous system, are thought to exhibit digital and analog properties. Alpha-synuclein(α-syn) proteins are of high importance to sustaining LTP in the brain. In this thesis, the most suitable platform for communication between two yeast cells and the passage of α-syn proteins through channels is optimized and designed. It refers to nerve cells in the computer environment by yeast cells in the simulation program. A channel that enables the communication of two yeast cells was designed and these yeast cells were placed in the traps located at the entrances of the channels. The activating agent was sent to produce α-syn of yeast cells in the A channel. Αlpha-synuclein protein, which is synthesized from yeast cells in the A channel, has passed through the channel and attached to the NDMA receptor in the other yeast cell in the B channel. Then, LTP was provided by activating the α-syn protein bound to the NDMA receptor in a balanced manner with Ca^+ions. Irregularity in the ratio of protein Ca^+ and α-syn prevents the formation of long term potentiation and causes Parkinson's disease. Optimization studies were carried out in microfluidic chip design. The number of channels along with the microfluidic chip, the width of chamber A and B, the width of the communication channel, the distance between communication channels, the length of yeast cells chamber, the length of yeast cells communication channel, the inlet-outlet radius of chamber A and B were determined. As a result of these determinations, it was observed how each parameter affects diffusion. The greater diffusion indicates that the amount of α-syn protein passes more from chamber A to chamber B. It was also observed that some parameters started diffusion earlier. Therefore, it enabled more yeast cells to interact. Computer modeling and simulation were applied as a very useful tool for improvements in the design of microfluidic chip geometry, as well as for the optimization of the technological and functional parameters. In this thesis, COMSOL Multiphysics, which is the most used in microfluidic systems, is used in two projects for microfluidic chip design and simulations within the designed chip.
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ÖgeSynthesis of folate receptor 1 targeted dye-conjugated peptides for use in positron emission tomography imaging systems(Graduate School, 2022-01-26) Cin, Derya ; Alptürk, Onur ; Yılmaz, Özgür ; 513191022 ; Nanoscience and Nanoengineering ; Nano Bilim ve Nano MühendislikNowadays, it is tried to find solutions for human beings to have a long and high-quality life, increase the number of studies in the field of health, and detect diseases that become difficult to treat with their progress. Cancer is one of the first causes of death statistics in official records in the world and Turkey. It is known that the diagnosis of cancer is difficult and takes time, and the number of cases continues to increase rapidly day by day. Because of the metabolism change in cancer cells, the cells continue to grow and divide instead of dying. Cancer factors; inherited mutations can be internal, such as hormones, or acquired environmental, such as carcinogens, radiation, infectious organisms, and lifestyle. By imaging the changes caused by cancer in cells, information about the stage of cancer can be obtained. Cancer researchers want to detect cells where cancers develop, identify biomarkers of cancers early, and create treatment plans for cancer. Proteins produced by tumor cells can be used as biomarkers to evaluate disease processes. Molecular imaging (MI) aims to combine patient and disease-specific molecular information and is an interdisciplinary area covering a wide range of sciences when is used in the diagnosis and treatment of diverse disease genres. For this purpose, targeted cell-specific chemical biomolecules are delivered to the organism by labeled radioactive isotopes. The imaging method to be utilized varies specifically according to the disease state. Positron emission tomography (PET), which has become more advanced with the integration of scanners such as computerized tomography (CT) used in the imaging of cancer, is one of the several imaging methods widely used in the diagnosis of cancer today. Since radioisotope imaging agents are required for imaging in PET devices, studies for their development are increasing day by day. Peptides are used as ligands/agents in imaging cancer imaging, thanks to their properties such as high selectivity and high affinity, ease of synthesis and chemical stability, quick removal from blood, and low immunogenicity/safety for cell surface proteins. Due to the metabolic rate of cancer cells, more folic acid is produced in these cells than in normal healthy body cells, and this uncontrolled increase has led to its use in cancer imaging studies. Peptide-based imaging agents are used for molecular imaging by binding to target cancer receptors such as Folate Receptor 1 (FOLR1) of tumor cells. Molecules that can bind to the FOLR1 receptor with high sensitivity and affinity were synthesized by the Solid Phase Peptide Synthesis (SPPS) method. The peptides KWGFR, KLWWN, KFLSW, KWIAG, KWSYW, KGWRN, and KSYFA were selected from the peptide library and successfully synthesized. Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) was used to purify the peptides and Liquid Chromatography-Mass Spectrometry (LC-MS) was utilized for peptide characterization. Finally, the imaging agent will be obtained by conjugating the peptide-based signaling agent labeled with the 68Ga isotope.