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)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 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.Conference Object Citation - Scopus: 2Label-Free Detection of Rare Cancer Cells Using Deep Learning and Magnetic Levitation Principle(SPIE, 2021) Delikoyun, Kerem; Demir, Ali Aslan; Tekin, Hüseyin CumhurMagnetic levitation is an effective tool for separating target cells within a heterogeneous solution by utilizing density differences among cell lines. However, magnetic levitation cannot be used to identify target cells which have similar density profile as the other cells in the solution. Therefore, accuracy of cell identification can dramatically reduce. In this study, we introduce, for the first time, the use of deep learning-based object detection approach for label-free identification of rare cancer cells within levitated cells. As a result, our novel and hybrid detection strategy could be used to identify circulating tumor cells for diagnosis and prognosis of cancer. © 2021 SPIE.Conference Object Citation - Scopus: 2Magnetic Levitation-Based Protein Detection Using Lensless Digital Inline Holographic Microscopy(The Chemical and Biological Microsystems Society (CBMS), 2019) Yaman, Sena; Delikoyun, Kerem; Tekin, Hüseyin CumhurWe present a portable protein detection platform based on magnetic levitation principle integrated with a lensless imaging system. In the platform, polymer microspheres are used to capture selectively target proteins and magnetic nanoparticle labels. The imaging system monitors the levitation height change of polymer microspheres with respect to the presence of target protein on their surfaces. This system enables the detection of target proteins down to ng/mL levels in a short time. © 2019 CBMS-0001.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.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; Yılmaz, Esra; Sarıgil, Öykü; Tekin, Hüseyin Cumhur; Özçivici, EnginMagnetic 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) Anıl İnevi, Müge; Sarıgil, Öykü; Yaman, Sena; Yalçın Özuysal, Özden; Meşe, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, EnginGravity 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.