Search

troke is the third leading cause of morbidity and mortality worldwide. Many deleterious cellular pathways have been proposed to explain the molecular pathogenesis of this clinically devastating disease [1, 2]. The pathophysiology of stroke is complex and involves not only calcium and glutamate-mediated excitotoxicity but also various inflammatory pathways, disturbance of ionic balance, increased production of free radicals and neuronal cell apoptosis [3-5]. Besides its critical role for ion homeostasis in the central nervous system, disturbance of BBB integrity plays a significant role in stroke pathogenesis [6-8]. In this respect, recent studies have established that loss of BBB integrity and secondary loss of ion regulation may lead to brain edema and subsequent brain damage after cerebral ischemia [7, 9, 10]. This suggests that stabilization of the BBB could be brain protective, although recent studies failed to confirm this [11-13]. Moreover, data show that cerebral ischemia-induced BBB disruption is increased by 24 hours after middle cerebral artery occlusion [14], thus providing only a short window for transport of macromolecular drugs into the infarcted brain [14, 15]. This therapeutic time-frame effectively limits treatment efficacy due to an inability to achieve a sufficiently high dose of drug in the target brain area [15]. Therapeutic agents are often difficult to administer to the brain due to BBB prevention of passage for systemically administered molecules and proteins [16-18]. Because of this pharmacological therapies have made limited progress, and much effort is now being directed to identify compounds that accumulate more efficaciously in the diseased brain.

Mikro parçacıkların yakalanmasını ve iki boyutlu manipülasyonunu sağlamak için sıra sütunlarına adreslenmiş CMUT dizilerinin mikroakışkan kanal ile birleştirilermesi tezin temel konusunu oluşturmaktadır. Bu çalışmada hedef frekansı 2.5 MHz olan çok katmanlı düzlemsel bir rezonatör tasarlanmış ve simülasyonları yapılmıştır. Sonlu elemanlar modellemesi ve simülasyonları ile bir parçacığın CMUT'i aktive ederek sıvı kanalı içindeki hem yanal hem de eksensel yönlerde sıkıştırabileceği ve manipüle edilebileceği gösterilmiştir. Önerilen platform ile 10um yarıçapında bir polistiren parçacığına etki eden akustik radyasyon kuvveti, FEM sonuçları kullanılarak hesaplanmıştır. Optimize edilmiş parametrelere dayanarak, anodik yapıştırma teknolojisini kullanarak bir cam taban üzerinde 32x32 elemanlı sıra / sütun adresli 2 boyutlu CMUT dizisinin üretimi gerçekleştirilmiştir. Bu yaklaşım, mikro parçacık tutma ve işleme için maliyet etkin ve kolayca uygulanabilir bir çözüm sağlamaktadır. The thesis introduces a concept of combining row column addressed CMUT arrays with microfluidic channel to enable trapping and two-dimensional manipulation of micro-particles.In this work a multilayer planar resonator with a target frequency of 2.5 MHz was designed and simulated. It was shown through finite element modeling and simulations that a particle can be trapped and manipulated both in lateral and axial directions inside the fluid channel by activating CMUT elements. Acoustic radiation force acting on a polystyrene particle of 10-um Radius were calculated using the FEM results. Based on the optimized parameters we fabricated a 32x32-element row/column-addressed 2D CMUT array on a glass substrate using anodic bonding technology. This approach provides a cost-effective and easily implementable solution to micro-particle trapping and handling. 75