Browsing by Subject "Microfluidic chips"
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Item Open Access Advancing 3D printed microfluidics with computational methods for sweat analysis(SPRINGER Wien, 2024-02-27) Ece, Emre; Ölmez, Kadriye; Hacıosmanoğlu, Nedim; Atabay, Maryam; İnci, FatihThe intricate tapestry of biomarkers, including proteins, lipids, carbohydrates, vesicles, and nucleic acids within sweat, exhibits a profound correlation with the ones in the bloodstream. The facile extraction of samples from sweat glands has recently positioned sweat sampling at the forefront of non-invasive health monitoring and diagnostics. While extant platforms for sweat analysis exist, the imperative for portability, cost-effectiveness, ease of manufacture, and expeditious turnaround underscores the necessity for parameters that transcend conventional considerations. In this regard, 3D printed microfluidic devices emerge as promising systems, offering a harmonious fusion of attributes such as multifunctional integration, flexibility, biocompatibility, a controlled closed environment, and a minimal requisite analyte volume—features that leverage their prominence in the realm of sweat analysis. However, formidable challenges, including high throughput demands, chemical interactions intrinsic to the printing materials, size constraints, and durability concerns, beset the landscape of 3D printed microfluidic devices. Within this paradigm, we expound upon the foundational aspects of 3D printed microfluidic devices and proffer a distinctive perspective by delving into the computational study of printing materials utilizing density functional theory (DFT) and molecular dynamics (MD) methodologies. This multifaceted approach serves manifold purposes: (i) understanding the complexity of microfluidic systems, (ii) facilitating comprehensive analyses, (iii) saving both cost and time, (iv) improving design optimization, and (v) augmenting resolution. In a nutshell, the allure of 3D printing lies in its capacity for affordable and expeditious production, offering seamless integration of diverse components into microfluidic devices—a testament to their inherent utility in the domain of sweat analysis. The synergistic fusion of computational assessment methodologies with materials science not only optimizes analysis and production processes, but also expedites their widespread accessibility, ensuring continuous biomarker monitoring from sweat for end-users.Item Open Access Capture and release of biomolecules and cancer cells via smart materials integrated microfluidic chips(2022-08) Sağdıç, KutayPrevalent 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.Item Open Access Microfluidic chip-based systems for monitoring cancer therapy(2022-12) Yılmaz, Eylül GülşenIn 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.Item Embargo Thermoresponsive polymer integrated metasurface sensor for capture and release of extracellular vesicles in real-time(2025-02) Küçük, Beyza NurExtracellular vesicles (EVs) play pivotal tasks in intracellular communication, carrying biomolecules such as proteins, lipids, and nucleic acids that reflect the physiological state of their originating cells. Isolating EVs purely from complex and protein-rich matrixes is crucial for understanding cellular processes and disease progression. The gold standard method for isolating EVs is ultracentrifugation, yet it has severe obstacles in terms of requiring expensive equipment, non-vesicular impurities, and possible damage on the EV surface. Owing to these drawbacks, their further analyses, isolation and detection through their surface markers are challenging. This study aims to integrate a smart thermoresponsive polymer with a metasurface plasmonic sensor, which is further decorated with anti-CD63 antibodies to capture EVs derived from MCF-7 breast cancer cells as a model system. We later isolate (release) these EVs by simply altering the local temperature above the lower critical temperature (LCST) of the polymer. Basically, the thermoresponsive polymer exhibits hydrophilic characteristics below its LCST and becomes hydrophobic when the temperature is increased above the LCST. The optic plasmonic sensor has a well-defined nanoperiodic array, presenting surface plasmons while exciting the surface with a normal angle of incident light. Therefore, the metamaterial sensor denotes real-time and label-free detection of EV binding and release events. This enables the quantitative analysis of EVs. In a nutshell, leveraging the distinctive thermoresponsive characteristics of the polymer, we presented a novel methodology designed to selectively immobilize EVs through antibody interactions and subsequently release them by elevating the temperature. This process enables the isolation of EVs with a high degree of purity, free from non-specific molecular contaminants. Consequently, our pioneering approach opens a promising new way for studying EVs and their surface markers in great detail, unrestricted by the limitations of conventional separation techniques, and contributes to the understanding of complex cellular processes and the subtle development of illnesses.