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Surface acoustic wave based sonoporation microsystems forsingle tumor cell applications

Başlık çevirisi mevcut değil.

  1. Tez No: 759388
  2. Yazar: BURAK YILDIRIM
  3. Danışmanlar: Belirtilmemiş.
  4. Tez Türü: Doktora
  5. Konular: Bilgisayar Mühendisliği Bilimleri-Bilgisayar ve Kontrol, Computer Engineering and Computer Science and Control
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2021
  8. Dil: İngilizce
  9. Üniversite: University of Miami
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 145

Özet

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Özet (Çeviri)

Biosensors and bioelectronics have made a significant impact on the treatment of many diseases. Developments and growing interest in micro and nano scale technologies have produced advancements in the biology field and resulted in smaller systems with higher accuracy under the multitude of approaches. These small systems usually target cells, proteins, DNA, drugs, etc. to diagnose or treat various diseases. Likewise, analysis of a single cell or a small number of cells has usually been performed using similar-sized systems. However, the task of observing single cells is a challenging task during diagnostic or treatment protocols. This challenge is more pronounced for studies that require sensitive handling of valuable, fragile, rare, and hard in order to collect samples such as tumor cells in transfection studies. This dissertation proposes a new surface acoustic wave (SAW) based sonoporation microsystem for therapeutic applications. The system essentially consists of interdigitated transducers (IDT) operated in Rayleigh mode along with a polymer reservoir fabricated in front of IDTs with the purpose of applying a controllable pressure field through tumor cells in the reservoir. The system has been simulated using finite element analysis (FEA) methods to interrogate actual pressure fields applied to cells by varying frequency and power. To verify the validity of this analysis, this dissertation also includes diagnostic tools, which consist of piezoelectric film characterization, and identifying liquid and cells properties using these diagnostic tools. The first diagnostic tool is a comprehensive characterization of a very smooth, c-axis oriented, highly piezoelectric, and electrically resistive ZnO thin film deposited by a radio frequency magnetron sputtering system on SiO2/Si substrate. Properties of the thin film such as surface roughness, crystallography, stoichiometry, and electrical resistivity are measured. Then, SAW devices with three different operating frequencies are fabricated on top of the film and tested by comparing FEA results. The second is Rayleigh waves-based SAW liquid sensors with integrating microchannel. The SAW device is first modeled with a microchannel and then is analyzed using FEA. Precise fabrication, alignment, and bonding of polydimethylsiloxane microchannels on diced Y-Z lithium niobate substrates are accomplished. Low glycerin concentrations in deionized water are analyzed. The third is a SAW biosensor capable of sensing single biological cells and microbeads utilizing microreservoirs that allows direct interaction with single cells or microbeads. Elimination of acoustoelectric coupling is demonstrated by a comprehensive FEA. After the optimization and completion of a novel fabrication sequence for the sensor, varying sizes of microbeads and tumor cells, i.e., MCF-7 and MDA-MB-231, are tested separately on an individual basis. Based on these studies, the high-frequency elastic modulus of MCF-7 and MDA-MB-231 are estimated. Results presented in this dissertation show that stiffness is a possible biomarker for the aggressiveness of the tumor. The results obtained throughout the diagnostic tools are inserted into the FEA model of the proposed sonoporation microsystem. A SAW device with an operating frequency of 47.84 MHz is produced by MEMS scale devices integrated with microfluidics. For the experiment, MDA-MB-231 breast cancer cells were tested for viability and intracellular transportation. Changes in color intensity of a single cell were monitored by a fluorescent microscope in real-time. The microsystem achieved a sonoporation efficiency of 72.73 % while keeping the cell viability at a minimum of 89.80 % without employing any ultrasound contrast agents. These proof-of-concept results show that, by applying SAWs, significant progress in directed pressure application is achievable while also maintaining high cell viabilities for further downstream testing and processing. Therefore, the sonoporation microsystem can be readily integrated with other biosensors or single-cell analysis equipment paving the way for holistic cancer diagnosis or therapeutics studies in a selfcontained environment on a stand-alone platform. In addition, high precision control of acoustic pressure delivered to cells by varying power, frequency, duration of exposure, signal shape, and duty cycle are possible for a range of target sonoporation rates and pore sizes

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