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.Conference Object Biofabrication by Magnetic Levitational Assembly of Cells Into Defined 3d Cellular Structures(Mary Ann Liebert, 2022) Arslan Yıldız, AhuIn the field of tissue engineering 3D (three dimensional) cell culture studies have increased over the years since they are the closest models of real tissues. Compared to the 2D models, there is a big improvement on cell growth, morphology, differentiation, gene and protein expression when 3D system is utilized. Because of these advantages 3D cell culture is commonly used for tissue engineering, artificial organ technologies, regenerative medicine, drug development, drug screening and stem cell studies. Despite promising advances in these areas, there are still unmet needs to completely fulfill all requirements. Sophisticated tools, methodologies and materials are still required for further development in tissue engineering; especially for cellular assembly, single cell level control, easy control over biofabrication system, direct forward cellular imaging and analysis. Recently, magnetic levitation technology that overcomes most of the above mentioned problems, has been utilized for the formation of 3D cellular structures. Magnetic levitational assembly of cells provide rapid, simple, cost-effective 3D cell culture formation while ensuring scaffold-free microenvironment.Article Citation - Scopus: 6Sensitive and Rapid Protein Assay Via Magnetic Levitation(Elsevier, 2022) Sözmen, Alper Baran; Arslan Yıldız, AhuMagnetic levitation (MagLev) is a newly emerging methodology for biosensing that provides a density-based analysis, which is highly sensitive and versatile. In this study, a magnetic levitation based sensor platform was used for protein detection; and sensor platform optimization was performed for both sensitivity and resolution. Bovine Serum Albumin (BSA) was used as a model protein and detection of BSA was carried out by antibody functionalized polystyrene microspheres (PSMs). Various sizes of PSMs were examined and their performances were compared by statistical analyses in terms of limit of detection (LOD), sensitivity, and resolution. Quantification of the protein was done based on the magnetic levitation height differences of antibody functionalized PSMs. For optimization of the methodology, varied PSMs were utilized, and standardization of PSM diameter, concentration of the antibody to be functionalized, and PSM dilution rates were carried out. In conclusion, 20 μm PSMs diluted to 0.005% W/V and functionalized with anti-BSA antibody at a concentration of 28 μg/ml were determined to provide the best resolution for BSA detection. A dynamic range of 100 nM to 1 mM was observed with an LOD value of 4.1 ng/ml. This sensing platform promises a novel approach with a diverse application field and it provides rapid, consistent, and reproducible results with high resolution and sensitivity.Conference Object Citation - Scopus: 1Magnetic Levitation-Based Adipose Tissue Engineering Using Horizontal Magnet Deployment(IEEE, 2020) Sarıgil, Öykü; Tekin, Hüseyin Cumhur; Anıl İnevi, Müge; Anıl İnevi, Müge; Yılmaz, Esra; Sarıgil, Öykü; Özçelik, Özge; Meşe Özçivici, Gülistan; Meşe, Gülistan; Meşe Özçivici, Gülistan; Tekin, H. CumhurMagnetic 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) Anıl İnevi, Müge; Ünal, Yağmur Ceren; Yaman, Sena; Tekin, H. Cumhur; Meşe, Gülistan; Meşe, GülistanLabel-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; Yaman, Sena; Yılmaz, Esra; Sarıgil, Öykü; Anıl İnevi, Müge; Telli, Kübra; Yalçın Özuysal, ÖzdenIn 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.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; Anıl İnevi, Müge; Özçivici, Engin; Tekin, Hüseyin CumhurSeparation 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.Conference Object Citation - Scopus: 2Density-Based Separation of Microparticles Using Magnetic Levitation Technology Integrated on Lensless Holographic Microscopy Platform(Institute of Electrical and Electronics Engineers Inc., 2019) Delikoyun, Kerem; Yaman, Sena; Tekin, Hüseyin CumhurMicroparticle/cell separation is one of the most important applications in the field of biomedical sciences particularly for cell sorting and protein assays. There are variety of different separation technologies introduced in the literature that the main limitations are large amount of sample, expensive chemical use besides of requirement of a labeling procedure (i.e. fluorescent/magnetic labeling), complex machinery, and high operational costs. Magnetic levitation-based separation offers simple, rapid and precise separation of microparticles based on their densities by suspending them in a glass microcapillary between two opposing magnets. Traditionally, magnetic levitation-based microparticle separation and identification procedure is performed by imaging under bulky microscopes composed of fragile and expensive optics and require trained personnel to operate which makes the whole procedure costly, time consuming and prone to human error. Lensless digital inline holographic microscope (LDIHM) eliminates the need for sophisticated optics by replacing simple illumination and recording scheme that can be reduced into few widely-Available and cost-effective components. Thus, inspection procedure is mostly carried out on digitally processing captured holograms so that dependency on optical components and human error is dramatically reduced alongside using cost-effective and handheld device. Here, we introduce a novel hybrid platform that brings the advantages of magnetic levitation system with lensless digital inline holographic microscope for precise separation and identification of microparticles based on their densities. In the platform, it was shown that 1.026 g/mL and 1.090 g/mL microparticles were successfully identified. © 2019 IEEE.Conference Object Citation - WoS: 1Citation - Scopus: 3Microfluidic Platform for Sorting Materials Based on Their Densities Using Magnetic Levitation(Institute of Electrical and Electronics Engineers Inc., 2019) Yılmaz, Esra; Özçivici, Engin; Tekin, Hüseyin CumhurCirculating Tumor Cells (CTCs) play a vital role in cancer diagnosis, prognosis and personalized medicine. However, CTCs are extremely rare in blood (i.e., down to 1-100 CTC per 1 mL human blood) and hard to isolate because of the heterogeneity of CTCs in biomarker expression. The current CTC separation and identification techniques use numerous differences between cells such as size, electric charges, density and expression of cell surface markers. However, these techniques have many limitations in terms of laborious sample preparation steps, inconsistent results caused by low specificity and efficiency and high cost. Hence, there is no standard method for isolating CTCs yet. With this study, it was aimed to fill the gap in CTC isolation and identification by proposing to develop a new method based on magnetic levitation principle, which has recently been demonstrated as a highly acceptable method for biological characterization of cells and monitoring of their cellular events. In this study, we have developed a new label-free microfluidic sorter to separate microparticles/cells based on their densities using magnetic levitation principle. Two different density microparticles (1.02 g/mL and 1.09 g/ mL) have been sorted and quantified in a continuous flow using a set of permanent magnets located in a 3D printed structure surrounding the microfluidic channel. This device can be used for rapid, low cost and label-free in-vitro diagnosis of cancer by sorting CTCs from whole blood in a high-Throughput manner. The sorted cells might further be used for downstream analysis for personalized and precision medicine. © 2019 IEEE.