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; Anıl İnevi, Müge; Yılmaz, Esra; Yalçın Özuysal, Özden; Özçelik, Özge Solmaz; Özçivici, Engin; Anıl İnevi, Müge; Tekin, Hüseyin Cumhur; Günyüz, Zehra Elif; Yalçın Özuysal, Özden; Özçivici, Engin; Tekin, Hüseyin Cumhur; 03.01. Department of Bioengineering; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of TechnologyCirculating 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)Conference Object Citation - Scopus: 1Magnetic Levitation-Based Adipose Tissue Engineering Using Horizontal Magnet Deployment(IEEE, 2020) Tekin, Hüseyin Cumhur; Anıl İnevi, Müge; Sarıgil, Öykü; Meşe Özçivici, Gülistan; Yılmaz, Esra; Sarıgil, Öykü; Özçelik, Özge; Meşe Özçivici, Gülistan; Meşe, Gülistan; Meşe Özçivici, Gülistan; Tekin, H. Cumhur; 01. Izmir Institute of Technology; 03.01. Department of Bioengineering; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of ScienceMagnetic levitation is a promising technique for tissue engineering with contact- and label-free approach. Levitation-based biofabrication systems emerge as a simple, rapid and versatile alternative to traditional tissue culture systems, since biofabrication specs can easily be tailored via magnet shape and configuration. This study aims at possible magnetic levitation systems for culture of adipose tissue cells. In this study, we performed two different magnet configurations, vertical and horizontal deployment, in an effort to be utilized in adipose tissue engineering.Conference Object Assessment of Cell Cycle and Viability of Magnetic Levitation Assembled Cellular Structures(IEEE, 2020) Meşe Özçivici, Gülistan; Tekin, Hüseyin Cumhur; Yaman, Sena; Anıl İnevi, Müge; Ünal, Yağmur Ceren; Meşe, Gülistan; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of ScienceLabel-free magnetic levitation is one of the most recent Earth-based in vitro techniques that simulate the microgravity. This technique offers a great opportunity to biofabricate scaffold-free 3-dimensional (3D) structures and to study the effects of microgravity on these structures. In this study, self-assembled 3D living structures were fabricated in a paramagnetic medium by magnetic levitation technique and effects of the technique on cellular health was assessed. This magnetic force-assisted assembly system applied here offers broad applications in several fields, such as space biotechnology and bottom-up tissue engineering.Article Citation - WoS: 24Citation - Scopus: 30Hologlev: a Hybrid Magnetic Levitation Platform Integrated With Lensless Holographic Microscopy for Density-Based Cell Analysis(American Chemical Society, 2021) Delikoyun, Kerem; Anıl İnevi, Müge; Yaman, Sena; Yalçın Özuysal, Özden; Sarıgil, Öykü; Telli, Kübra; Yalçın Özuysal, Özden; 01. Izmir Institute of Technology; 03.01. Department of Bioengineering; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of ScienceIn clinical practice, a variety of diagnostic applications require the identification of target cells. Density has been used as a physical marker to distinguish cell populations since metabolic activities could alter the cell densities. Magnetic levitation offers great promise for separating cells at the single cell level within heterogeneous populations with respect to cell densities. Traditional magnetic levitation platforms need bulky and precise optical microscopes to visualize levitated cells. Moreover, the evaluation process of cell densities is cumbersome, which also requires trained personnel for operation. In this work, we introduce a device (HologLev) as a fusion of the magnetic levitation principle and lensless digital inline holographic microscopy (LDIHM). LDIHM provides ease of use by getting rid of bulky and expensive optics. By placing an imaging sensor just beneath the microcapillary channel without any lenses, recorded holograms are processed for determining cell densities through a fully automated digital image processing scheme. The device costs less than $100 and has a compact design that can fit into a pocket. We perform viability tests on the device by levitating three different cell lines (MDA-MB-231, U937, D1 ORL UVA) and comparing them against their dead correspondents. We also tested the differentiation of mouse osteoblastic (7F2) cells by monitoring characteristic variations in their density. Last, the response of MDA-MB-231 cancer cells to a chemotherapy drug was demonstrated in our platform. HologLev provides cost-effective, label-free, fully automated cell analysis in a compact design that could be highly desirable for laboratory and point-of-care testing applications.Article Citation - WoS: 22Citation - Scopus: 26Magnetic Levitation Assisted Biofabrication, Culture, and Manipulation of 3d Cellular Structures Using a Ring Magnet Based Setup(Wiley, 2021) Anıl İnevi, Müge; Delikoyun, Kerem; Özçivici, Engin; Meşe Özçivici, Gülistan; Tekin, Hüseyin Cumhur; 03.01. Department of Bioengineering; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of TechnologyDiamagnetic levitation is an emerging technology for remote manipulation of cells in cell and tissue level applications. Low-cost magnetic levitation configurations using permanent magnets are commonly composed of a culture chamber physically sandwiched between two block magnets that limit working volume and applicability. This work describes a single ring magnet-based magnetic levitation system to eliminate physical limitations for biofabrication. Developed configuration utilizes sample culture volume for construct size manipulation and long-term maintenance. Furthermore, our configuration enables convenient transfer of liquid or solid phases during the levitation. Before biofabrication, we first calibrated/ the platform for levitation with polymeric beads, considering the single cell density range of viable cells. By taking advantage of magnetic focusing and cellular self-assembly, millimeter-sized 3D structures were formed and maintained in the system allowing easy and on-site intervention in cell culture with an open operational space. We demonstrated that the levitation protocol could be adapted for levitation of various cell types (i.e., stem cell, adipocyte and cancer cell) representing cells of different densities by modifying the paramagnetic ion concentration that could be also reduced by manipulating the density of the medium. This technique allowed the manipulation and merging of separately formed 3D biological units, as well as the hybrid biofabrication with biopolymers. In conclusion, we believe that this platform will serve as an important tool in broad fields such as bottom-up tissue engineering, drug discovery and developmental biology.Article Citation - WoS: 22Citation - Scopus: 24Scaffold-Free Biofabrication of Adipocyte Structures With Magnetic Levitation(John Wiley and Sons Inc., 2021) Yalçın Özuysal, Özden; Meşe Özçivici, Gülistan; Fıratlıgil Yıldırır, Burcu; Ünal, Yağmur Ceren; Özçivici, Engin; Sarıgil, Öykü; Anıl İnevi, Müge; Tekin, Hüseyin Cumhur; Yalçın Özuysal, Özden; Özçivici, Engin; Meşe, Gülistan; Sarıgil, Öykü; Özçivici, Engin; Anıl İnevi, Müge; Meşe Özçivici, Gülistan; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of ScienceTissue engineering research aims to repair the form and/or function of impaired tissues. Tissue engineering studies mostly rely on scaffold-based techniques. However, these techniques have certain challenges, such as the selection of proper scaffold material, including mechanical properties, sterilization, and fabrication processes. As an alternative, we propose a novel scaffold-free adipose tissue biofabrication technique based on magnetic levitation. In this study, a label-free magnetic levitation technique was used to form three-dimensional (3D) scaffold-free adipocyte structures with various fabrication strategies in a microcapillary-based setup. Adipogenic-differentiated 7F2 cells and growth D1 ORL UVA stem cells were used as model cells. The morphological properties of the 3D structures of single and cocultured cells were analyzed. The developed procedure leads to the formation of different patterns of single and cocultured adipocytes without a scaffold. Our results indicated that adipocytes formed loose structures while growth cells were tightly packed during 3D culture in the magnetic levitation platform. This system has potential for ex vivo modeling of adipose tissue for drug testing and transplantation applications for cell therapy in soft tissue damage. Also, it will be possible to extend this technique to other cell and tissue types.Conference Object Citation - WoS: 7Citation - Scopus: 7Cell Separation With Hybrid Magnetic Levitation-Based Lensless Holographic Microscopy Platform(Institute of Electrical and Electronics Engineers Inc., 2019) Delikoyun, Kerem; Yaman, Sena; Yaman, Sena; Delikoyun, Kerem; Anıl İnevi, Müge; Tekin, Hüseyin Cumhur; Özçivici, Engin; Özçivici, Engin; Tekin, Hüseyin Cumhur; Anıl İnevi, Müge; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologySeparation of target cells in a heterogeneous solution is of great importance for clinical studies especially for immunology and oncology. Separated cells can be used for diagnostic applications ranging from whole blood counting to isolation of circulating tumor cells (CTC) for personalized medicine. Recent separation technologies rely on labelling and identifying target cells with variety of labelling principle such as fluorescence or magnetic tags. However, they require labor-intensive processes, long analysis time, and expensive chemical reagents and instrumentation. Hence, their usage is limited to well-equipped centralized laboratories. There is a need for a rapid, sensitive, low-cost and automated cell separation technology to disseminate usage of this technology even in rural areas. Magnetic levitation is a powerful cell separation method, which distinguishes cells based on their levitation heights depending on cell density. However, magnetic levitation-based separation technologies require traditional, bulky and expensive microscopes for analysis. Lensless digital inline holographic microscopy (LDIHM) systems are composed of a simple illumination system containing an LED, a pinhole, and an imaging sensor for high-resolution microscopic imaging, which eliminates needs of highly fragile and expensive optics as in traditional microscopy. Here, we introduced a novel hybrid and portable cell separation platform, where magnetic levitation technology is integrated with LDIHM system for automated analysis of cell levitation heights. Using this platform, three different cell lines are successfully separated. Live and dead cells having distinguished levitation heights can be also identified in the platform.Book Part Citation - WoS: 13Citation - Scopus: 15Single Cell Densitometry and Weightlessness Culture of Mesenchymal Stem Cells Using Magnetic Levitation(Humana Press, 2020) Anıl İnevi, Müge; Özçivici, Engin; Yılmaz, Esra; Sarıgil, Öykü; Sarıgil, Öykü; Tekin, Hüseyin Cumhur; Tekin, Hüseyin Cumhur; Anıl İnevi, Müge; Özçivici, Engin; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringMagnetic levitation methodology enables density-based separation of microparticles/cells and sustains cell culture in different media. Levitation process can be accomplished via negative magnetophoresis (diamagnetophoresis), where the applied magnetic force compensates gravitational acceleration and the density of the diamagnetic object (e.g., cell) determines its levitation height. Here we describe a portable, sensitive, and cost-effective technology that uses the principles of magnetic levitation to measure single cell density and cell culture under desired conditions. © 2019, Springer Science+Business Media New York.Conference Object Citation - WoS: 3Citation - Scopus: 4Biofabrication of Cellular Structures Using Weightlessness as a Biotechnological Tool(IEEE, 2019) Yaman, Sena; Sarıgil, Öykü; Anıl İnevi, Müge; Yalçın Özuysal, Özden; Meşe Özçivici, Gülistan; Özçivici, Engin; Tekin, Hüseyin Cumhur; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of ScienceGravity is an important biomechanical signal effecting the morphology and function of organisms. Reduction of gravitational forces, as experienced during spaceflight, cause alterations in the biological systems. Magnetic levitation technique is one of the most recent ground-based technology to mimic weightlessness environment. In addition to providing a platform to investigate biological effects of the weightlessness, this platform presents a novel opportunity to biofabricate 3-dimensional (3D) structures in a scaffold-and nozzle-free fashion. In this study, various controllable self-assembled 3D living structures were fabricated via magnetic levitation technique. This strategy may offer an easy and cost-effective opportunity for a wide range of space biotechnology researches.Conference Object Citation - WoS: 4Citation - Scopus: 5Application of Magnetic Levitation Induced Weightlessness To Detect Cell Lineage(IEEE, 2019) Anıl İnevi, Müge; Sarıgil, Öykü; Meşe Özçivici, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, Engin; Tekin, Hüseyin Cumhur; Özçivici, Engin; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of ScienceIdentification and classification of bone marrow cells is an important step for molecular biology and therapeutic studies related to bone marrow disorders such as osteoporosis or obesity. In this study, we applied magnetic levitation technology to induce a weightlessness environment to detect adipocytes and osteoblasts based on their single cell density. This biotechnological method can be used for separation of heterogeneous populations such as bone marrow once adapted to a continuous microfluidic platform.