Browsing by Subject "Microfluidic chips"

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Open Access
Capture and release of biomolecules and cancer cells via smart materials integrated microfluidic chips
(2022-08) Sağdıç, Kutay
Prevalent clinical conditions are impacting notably on our daily lives and the global economy. Healthcare system is hence garnering more interest in developing innovative material-based technologies along with accurate surface chemistry and signal generation reactions to measure biomarkers for disease diagnosis. In particular, biomedical studies focus to diagnose complex cases such as cancer. For instance, there are some critical stages in cancer development and metastasis. Moreover, impractical, invasive methods, and the restricted repertoire of targeted therapies are driving factors for researchers to find out new monitoring techniques that anticipate the future journey of cancer cells. On the other hand, the analysis of bodily fluids containing circulating tumor cells (CTCs) and biomarkers allows more insight into detecting/monitoring cancer as early as possible, and it would provide more information than that of any single-site biopsies. Yet, implementing the current technologies focusing on CTC detection and isolation in the clinics have notable challenges, i.e., expensive reagents/assays, complex operation, lengthy processes, bio-compatibility, and the need for specialized personnel. In this thesis, we have designed a microfluidic chip to hurdle these existing challenges, and for this regard, we tuned the surface area of the chip by integrating bio-mimetic smart materials (different shapes of silica particles-coated with poly(N -isopropylacrylamide). Initially, we tested our strategy with model proteins for both capture and release aspects. The smart materials were then modified with anti-EpCAM antibodies to capture human breast cancer cells (MCF-7) as a cancer model. Once the cells were captured in the chip, they were released by simply altering the 3-dimensional structure of smart materials above to lower critical solution temperature. Herein, we have anticipated that the developed platform would resolve cost, bio-compatibility, applicability, complexity, and assay duration-related challenges of current technologies in this realm.
Open Access
Microfluidic chip-based systems for monitoring cancer therapy
(2022-12) Yılmaz, Eylül Gülşen
In tumor microenvironment, cancer cells are exposed to a range of fluid shear stresses (FSS); yet, current in vitro three-dimensional (3D) models have limitations to investigate the impact of biophysical stimuli on cancer mechanism and chemoresistance in a dynamic manner. In the past few decades, vital demand for exploring biological significance of mechanical forces has led to the development of several innovative approaches. One of these approaches is the integration of microfluidic systems into cancer studies. The use of microfluidic chips has garnered increasing attention since they offer ease-of-manipulation, high-throughput, less material/reagent consumption, and low-cost. On the other hand, the researches have stated explicitly that tumor-derived extracellular vesicles (EVs) regulate local and systemic milieu to drive the development and spread of cancer through nano- and micron-sized vesicles they carry. In this thesis, breast cancer cells (MCF-7) have been utilized as a model cancer system, and accordingly, they are cultivated through SF-coated microfluidic systems in order to mimic tumor microenvironment, exhibiting a more dynamic condition. Simultaneously, traditional static culture of MCF-7 cells is also performed as a control group in order to understand the impact of flow conditions. The effects of FSS on gene expression—in particular, EpCAM and CK-18 genes, which are highly expressed in MCF-7 cells— have been examined at the end of cell culturing process. In addition, cancer cells developing any resistance to anti-cancer drugs on the course of FSS have been investigated. In this regard, the cells are treated with either doxorubicin or docetaxel (anti-cancer drugs) in the cases of dynamic (microfluidic system) and static (tissue culture flask) culture conditions. Multi-Drug Resistance 1 (MDR-1) and Breast Cancer Resistance Protein (BCRP) gene expression levels have been assessed once anti-cancer treatment has been finalized. The final step of this study relies on the isolation and analysis of EVs from both static and dynamic conditions with the presence and absence of anti-cancer drug treatment. The utility of EVs has been evaluated deliberately as biomarkers for real-time monitoring of treatment efficacy.