Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - Scopus: 11Μdacs Platform: a Hybrid Microfluidic Platform Using Magnetic Levitation Technique and Integrating Magnetic, Gravitational, and Drag Forces for Density-Based Rare Cancer Cell Sorting(Elsevier, 2023) Keçili, Seren; Yılmaz, Esra; Özçelik, Özge Solmaz; Anıl İnevi, Müge; Günyüz, Zehra Elif; Yalçın Özuysal, Özden; Özçivici, Engin; Tekin, Hüseyin CumhurCirculating tumor cells (CTCs) are crucial indicators of cancer metastasis. However, their rarity in the bloodstream and the heterogeneity of their surface biomarkers present challenges for their isolation. Here, we developed a hybrid microfluidic platform (microfluidic-based density-associated cell sorting (µDACS) platform) that utilizes density as a biophysical marker to sort cancer cells from the population of white blood cells (WBCs). The platform utilizes the magnetic levitation technique on a microfluidic chip to sort cells based on their specific density ranges, operating under a continuous flow condition. By harnessing magnetic, gravitational, and drag forces, the platform efficiently separates cells. This approach involves a microfluidic chip equipped with a microseparator, which directs cells into top and bottom outlets depending on their levitation heights, which are inversely proportional to their densities. Hence, low-density cancer cells are collected from the top outlet, while high-density WBCs are collected from the bottom outlet. We optimized the sorting efficiency by varying the flow rates, and concentrations of the sorting medium's paramagnetic properties using standard densities of polymeric microspheres. To demonstrate the platform's applicability, we performed hybrid microfluidic sorting on MDA-MB-231 human breast cancer cells and U-937 human monocytes. The results showed efficient sorting of rare cancer cells (≥100 cells/mL) from serum samples, achieving a sorting efficiency of ∼70% at a fast-processing speed of 1 mL h−1. This label-free approach holds promise for rapid and cost-effective CTC sorting, facilitating in-vitro diagnosis and prognosis of cancer. © 2023 The Author(s)Review Citation - WoS: 52Citation - Scopus: 56Spheroid engineering in microfluidic devices(American Chemical Society, 2023) Tevlek, Atakan; Keçili, Seren; Özçelik, Özge Solmaz; Kulah, Haluk; Tekin, H. CumhurTwo-dimensional (2D) cell culture techniques are commonly employed to investigate biophysical and biochemical cellular responses. However, these culture methods, having monolayer cells, lack cell-cell and cell-extracellular matrix interactions, mimicking the cell microenvironment and multicellular organization. Three-dimensional (3D) cell culture methods enable equal transportation of nutrients, gas, and growth factors among cells and their microenvironment. Therefore, 3D cultures show similar cell proliferation, apoptosis, and differentiation properties to in vivo. A spheroid is defined as self-assembled 3D cell aggregates, and it closely mimics a cell microenvironment in vitro thanks to cell-cell/matrix interactions, which enables its use in several important applications in medical and clinical research. To fabricate a spheroid, conventional methods such as liquid overlay, hanging drop, and so forth are available. However, these labor-intensive methods result in low-throughput fabrication and uncontrollable spheroid sizes. On the other hand, microfluidic methods enable inexpensive and rapid fabrication of spheroids with high precision. Furthermore, fabricated spheroids can also be cultured in microfluidic devices for controllable cell perfusion, simulation of fluid shear effects, and mimicking of the microenvironment-like in vivo conditions. This review focuses on recent microfluidic spheroid fabrication techniques and also organ-on-a-chip applications of spheroids, which are used in different disease modeling and drug development studies.Review Citation - WoS: 23Citation - Scopus: 24Microfluidic-Based Technologies for Diagnosis, Prevention, and Treatment of Covid-19: Recent Advances and Future Directions(Springer, 2023) Tarım, Ergün Alperay; Anıl İnevi, Müge; Özkan, İlayda; Keçili, Seren; Bilgi, Eyüp; Başlar, Muhammet Semih; Özçivici, Engin; Öksel Karakuş, Ceyda; Tekin, Hüseyin CumhurThe COVID-19 pandemic has posed significant challenges to existing healthcare systems around the world. The urgent need for the development of diagnostic and therapeutic strategies for COVID-19 has boomed the demand for new technologies that can improve current healthcare approaches, moving towards more advanced, digitalized, personalized, and patient-oriented systems. Microfluidic-based technologies involve the miniaturization of large-scale devices and laboratory-based procedures, enabling complex chemical and biological operations that are conventionally performed at the macro-scale to be carried out on the microscale or less. The advantages microfluidic systems offer such as rapid, low-cost, accurate, and on-site solutions make these tools extremely useful and effective in the fight against COVID-19. In particular, microfluidic-assisted systems are of great interest in different COVID-19-related domains, varying from direct and indirect detection of COVID-19 infections to drug and vaccine discovery and their targeted delivery. Here, we review recent advances in the use of microfluidic platforms to diagnose, treat or prevent COVID-19. We start by summarizing recent microfluidic-based diagnostic solutions applicable to COVID-19. We then highlight the key roles microfluidics play in developing COVID-19 vaccines and testing how vaccine candidates perform, with a focus on RNA-delivery technologies and nano-carriers. Next, microfluidic-based efforts devoted to assessing the efficacy of potential COVID-19 drugs, either repurposed or new, and their targeted delivery to infected sites are summarized. We conclude by providing future perspectives and research directions that are critical to effectively prevent or respond to future pandemics.Conference Object Citation - WoS: 2Citation - Scopus: 2Portatif ve Düşük Maliyetli Merceksiz Holografik Mikroskop Platformu ile Nanoparçacık Tespiti(IEEE, 2020) Delikoyun, Kerem; Keçili, Seren; Tekin, Hüseyin CumhurIn the biological and medical science, detection of biomolecule at very low concentration (<100 pg/mL) is of great importance and it is extensively used in the diagnosis of diseases, drug response monitoring and cancer research. For biomolecule detection tests, captured biomolecules generate signals (fluorescence, color, etc.), which are analyzed by trained personnel in bulky, high cost and fragile devices. However, for clinical applications, the access to these tests is very difficult at resource-limited settings. Lensless holographic microscopy provides high resolution imaging of samples without the need of expensive and fragile optical elements (mirror, lens, filter, etc.) used in traditional imaging technologies. While this technology offers a robust, portable and low-cost design, it enables fully automated processing of the sample image with digital processing schemes and this can also help eliminate user error. In this study, lensless holographic microscopy platform, which can be used in surface coverage assays for the detection of biomolecules, is proposed. It has been shown that nanoparticles (700-1200 nm) used as labels in surface coverage assays for the detection of biomolecules could be sensed on the platform. Therefore, it is anticipated that biomolecules detection could be realized rapidly and sensitively with this easy-to-use and low-cost imaging platform at the location where the high-level health institutions are not available and even at point-of-care settings.Article Citation - WoS: 17Citation - Scopus: 22Adhesive Bonding Strategies To Fabricate High-Strength and Transparent 3d Printed Microfluidic Device(American Institute of Physics, 2020) Keçili, Seren; Tekin, Hüseyin CumhurRecently, the use of 3D printing technologies has become prevalent in microfluidic applications. Although these technologies enable low-cost, rapid, and easy fabrication of microfluidic devices, fabricated devices suffer from optical opaqueness that inhibits their use for microscopic imaging. This study investigates bonding strategies using polydimethylsiloxane (PDMS) and printer resin as interlayer materials to fabricate high-strength optically transparent 3D-printed microfluidic devices. First, we fabricated microfluidic structures using a stereolithography 3D printer. We placed 3D-printed structures on interlayer materials coated surfaces. Then, we either let these 3D-printed structures rest on the coated slides or transferred them to new glass slides. We achieved bonding between 3D-printed structures and glass substrates with UV exposure for resin and with elevated temperature for PDMS interlayer materials. Bonding strength was investigated for different interlayer material thicknesses. We also analyzed the bright-field and fluorescence imaging capability of microfluidic devices fabricated using different bonding strategies. We achieve up to twofold (9.1 bar) improved bonding strength and comparable fluorescence sensitivity with respect to microfluidic devices fabricated using the traditional plasma activated PDMS-glass bonding method. Although stereolithography 3D printer allows fabrication of enclosed channels having dimensions down to similar to 600 mu m, monolithic transparent microfluidic channels with 280 x 110 mu m(2) cross section can be realized using adhesive interlayers. Furthermore, 3D-printed microfluidic chips can be integrated successfully with Protein-G modified substrates using resin interlayers for detection of fluorescent-labeled immunoglobulin down to similar to 30 ng/ml. Hence, this strategy can be applied to fabricate high-strength and transparent microfluidic chips for various optical imaging applications including biosensing.