Lazer işleme ile geliştirilen mikroakışkan çip içerisinde su damlalarının boyutlarına bağlı sınıflandırılması ve anjiyojenez çalışmalarına yönelik mikroakışkan çip tasarımı
2019
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Advisor: Prof. Dr. Alper Kiraz
Abstract (EN)
We demonstrate an autonomous, high throughput and rigorous mechanism for sorting of droplets with different dimensions over inclined (10 degree), shallow (700 nm) and narrow (22 and 30 µm) guiding tracks defined by laser micromachining. We fabricated a microfluidic device containing two independent T-junctions and inlets for droplet generation allowing broad range of size and speed tuning as well as droplet merging before entering the Hele-Shaw channel hosting the guiding track. In the first part, we investigate partial guiding of different sizes of droplets under same host liquid flow conditions based on the three forces acting on the droplets namely drag force, frictional force and confinement force. For a bigger droplet, drag force being a quadratic function of droplet diameter dominates the confinement force causing the droplets leaving the inclined track earlier covering less vertical distance and guided partially. Secondly, as the speed of the droplet is increased by increasing the channel flow rate while keeping its size constant, higher drag force is exerted on the droplet once again causing partial guiding. Finally, we demonstrate sorting of smaller guided droplets coflowing with bigger unguided droplets as a result of merging from two inlets in the common tapered region just before entering the Hele-Shaw channel. For all the experiments, we have considered two chip designs with different guiding track widths (22 µm and 30 µm) and found that the droplets undergo stronger guiding for the case of wider track because of the higher confinement force. All experimental results are correlated with analytical model results incorporating droplet size, speed, interfacial tension, contact angle and realistic droplet shape by finite volume method. Microfluidic technology combined with tissue engineering has significantly increased the progress in cell biology and helped in understanding the physiological and pathophysiological transitions. PDMS due to its bio-compatibility, optical transparency and elasticity is widely used in fabrication of microfluidic devices for rapid prototyping to understand the 3D physiological microenvironment. We designed a novel microfluidic chip that incorporates a collagen hydrogel scaffold for 3D cell growth and enables controlled diffusion of medium through it. Thus, it is a convenient design that incorporates a hydrogel that mimicks the cellular microenvironment. Our design consists three parallel microchannels in contact with each other. By the unique height design, the hydrogel solution stays in the defined region and takes the shape of the collagen loading channel due to capillary action and surface tension effect. Angiogenesis; the formation of new capillaries from existing ones is mediated by endothelial cells. The hydrogel provides a porous 3D support which mediates the exchange of O2 and nutrients. We studied the response of endothelial cells by stimulating them with vascular endothelial growth factor (VEGF) that diffuses through the 3D hydrogel scaffold from biochemical channel to the cell channel inside a microfluidic chip. Our novel design provides a favorable microenvironment for Endothelial cells to grow sprouts under the influence of stimuli by having a wide contact area between the collagen loading channel and the side channels. We found that our design works for studying sprouting angiogenesis and can be used for mimicking 3D microenvironments. We also designed another microfluidic chip that will be used as an indicator of the angiogenic potential of a tumor. It incorporates cells trapping wells in one of the side channels for trapping tumor cells and can be grown to become tumor spheroids in a chip. The side channel enables the formation of spheroids from injected tumor cells on the chip. This design is different from the previous design in a sense that no stimulus in introduced directly in the chip rather the growth factors and molecules secreted by tumor spheroids in its microenvironment will trigger endothelial sprouts. Different type of tumors secrete different growth factors and molecules. By using our designed microfluidic chip the angiogenic tendency of different tumors spheroids can be studied.
Author
Dr. Ateeq Ur Rehman
Institution
How to Cite
Ateeq Ur Rehman (Doctorate thesis). Lazer işleme ile geliştirilen mikroakışkan çip içerisinde su damlalarının boyutlarına bağlı sınıflandırılması ve anjiyojenez çalışmalarına yönelik mikroakışkan çip tasarımı, 2019, Koç University.
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