Bioengineering / Biyomühendislik

Permanent URI for this collectionhttps://hdl.handle.net/11147/4529

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  • Conference Object
    A Glucuronoxylan-Based Bio-Ink Development: Characterization and Application
    (Wiley, 2023) Yıldırım, Ömer; Arslan Yıldız, Ahu; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Bioprinting is a trending technique that enables the fabrication of three­dimensional (3D) constructs in designed shapes and with desired properties. Bio­inks are one of the most significant components of bioprinting and the successful fabrication of 3D bioprinted constructs mostly depends on the features of bio­inks that would be used. New generation bio­inks that are soft and viscous enough, printable under low pressure, stable in cell culture, and have fast gelation mechanisms are ideal to be used in current bioprinting techniques. Hydrocolloids have said features and have similar properties to native ECM structures. Hence bio­inks that are developed from hydrocolloids can be utilized for mimicking of ECM structure of soft tissues. Polysaccharide­based hydrocolloids are ideal bio­ink candidates with their high waterholding capacity and biocompatibility. Here, a glucuronoxylan­based new­generation bio­ink was developed, and its printability was evaluated for 3D bioprinting applications. The glucuronoxylan­based hydrocolloid was obtained by water extraction of quince seeds and its utilization in bioprinting was investigated. Bio­ink characterization was done by FTIR and mechanical analysis. Bioprinting parameters were optimized assessing uniformity, pore factor, and shape fidelity. Then, the characterization of bioprinted constructs was performed by pore angle measurement, water­holding capacity analysis, protein adsorption, and cell viability assays. Bioprinted structures have high mechanical strength, suitable protein adsorption behavior, and water­holding capacity as high as 20­fold of its own weight, which is higher than other hydrogels that were used in soft tissue engineering. Moreover, the cell viability results of fibroblast cells in the bio­ink were high for long­term culture. In conclusion, findings show that the developed glucuronoxylan­based bio­ink is a biocompatible and promising bio­ink material for further tissue engineering applications.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 5
    Antioxidant and Antimicrobial Activities of Plants Grown in the Mediterranean Region
    (John Wiley and Sons Inc., 2022) Kaçar, D.; Bayraktar, Oğuz; Erdem, C.; Alamri, A.S.; Galanakis, C.M.; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Background: The main objective of this research was to identify plant species with possible bioactivities based on their total phenol content, antioxidant, and antimicrobial properties. Therefore, different parts of 42 plant species grown in the Mediterranean region were extracted with aqueous ethanol solutions to prepare extracts with antioxidant and antimicrobial activities, mainly resulting from their total phenol contents. No detailed laboratory data on the flora of this area exists regarding their total phenol contents and total antioxidant activities. Results: Yields of extraction for each plant material were determined. Extracts were characterized based on their total phenol contents, total antioxidant (both hydrophilic and lipophilic), and antimicrobial activities using Folin–Ciocalteu, Photochemiluminescence, disc diffusion, and microdilution methods, respectively. The extract of Hypericum empetrifolium had the relatively highest total water-soluble and lipid-soluble antioxidant activities. Sarcopoterium spinosum extract had relatively high total phenol content. Preliminary screening study was conducted with the disc diffusion method to evaluate the extracts' antimicrobial activities. 26 out of 42 plant species showed significant antimicrobial activities against the growth of microorganisms. Microdilution assays were performed to evaluate the most active plant species with their minimum inhibition concentrations. H. empetrifolium, Pistacia terebinthus, Arbutus unedo, and Cistus parviflorus were the most antimicrobial plant species among those investigated. CONCLUSION: The new potential sources for the isolation of bioactive natural compounds from specific plant species could be possible with the help of this present screening study. Isolated bioactive natural compounds can be utilized as raw materials in cosmetics, nutraceuticals, food supplements, and pharmaceutical industries. © 2022 Society of Chemical Industry.
  • Conference Object
    Biopatterning of 3d Cellular Structures Via Contactless Magnetic Manipulation for Drug Screening
    (Mary Ann Liebert, 2023) Onbas, Rabia; Arslan Yıldız, Ahu; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
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    On-Chip 3d Cell Culture Platform for Tumor Modeling and Drug Screening
    (2022) Yıldırım, Özüm; Arslan Yıldız, Ahu; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
  • Article
    Citation - WoS: 11
    Citation - Scopus: 14
    3D Bioprinting of mouse pre-osteoblasts and human MSCs using bioinks consisting of gelatin and decellularized bone particles
    (Iop Publishing Ltd, 2024) Kara, Aylin; Distler, Thomas; Akkineni, Ashwini Rahul; Tihminlioglu, Funda; Gelinsky, Michael; Boccaccini, Aldo R.; 03.02. Department of Chemical Engineering; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    One of the key challenges in biofabrication applications is to obtain bioinks that provide a balance between printability, shape fidelity, cell viability, and tissue maturation. Decellularization methods allow the extraction of natural extracellular matrix, preserving tissue-specific matrix proteins. However, the critical challenge in bone decellularization is to preserve both organic (collagen, proteoglycans) and inorganic components (hydroxyapatite) to maintain the natural composition and functionality of bone. Besides, there is a need to investigate the effects of decellularized bone (DB) particles as a tissue-based additive in bioink formulation to develop functional bioinks. Here we evaluated the effect of incorporating DB particles of different sizes (<= 45 and <= 100 mu m) and concentrations (1%, 5%, 10% (wt %)) into bioink formulations containing gelatin (GEL) and pre-osteoblasts (MC3T3-E1) or human mesenchymal stem cells (hTERT-MSCs). In addition, we propose a minimalistic bioink formulation using GEL, DB particles and cells with an easy preparation process resulting in a high cell viability. The printability properties of the inks were evaluated. Additionally, rheological properties were determined with shear thinning and thixotropy tests. The bioprinted constructs were cultured for 28 days. The viability, proliferation, and osteogenic differentiation capacity of cells were evaluated using biochemical assays and fluorescence microscopy. The incorporation of DB particles enhanced cell proliferation and osteogenic differentiation capacity which might be due to the natural collagen and hydroxyapatite content of DB particles. Alkaline phosphatase activity is increased significantly by using DB particles, notably, without an osteogenic induction of the cells. Moreover, fluorescence images display pronounced cell-material interaction and cell attachment inside the constructs. With these promising results, the present minimalistic bioink formulation is envisioned as a potential candidate for bone tissue engineering as a clinically translatable material with straightforward preparation and high cell activity.
  • Article
    Citation - Scopus: 3
    Development of Chrono-Spectral Gold Nanoparticle Growth Based Plasmonic Biosensor Platform
    (Elsevier, 2024) Sözmen, Alper Baran; Elveren, Beste; Erdoğan, Duygu; Mezgil, Bahadır; Baştanlar, Yalın; Yıldız, Ümit Hakan; Arslan Yıldız, Ahu; 01. Izmir Institute of Technology; 04.01. Department of Chemistry; 03.04. Department of Computer Engineering; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 04. Faculty of Science
    Plasmonic sensor platforms are designed for rapid, label-free, and real-time detection and they excel as the next generation biosensors. However, current methods such as Surface Plasmon Resonance require expertise and well-equipped laboratory facilities. Simpler methods such as Localized Surface Plasmon Resonance (LSPR) overcome those limitations, though they lack sensitivity. Hence, sensitivity enhancement plays a crucial role in the future of plasmonic sensor platforms. Herein, a refractive index (RI) sensitivity enhancement methodology is reported utilizing growth of gold nanoparticles (GNPs) on solid support and it is backed up with artificial neural network (ANN) analysis. Sensor platform fabrication was initiated with GNP immobilization onto solid support; immobilized GNPs were then used as seeds for chrono-spectral growth, which was carried out using NH2OH at varied incubation times. The response to RI change of the platform was investigated with varied concentrations of sucrose and ethanol. The detection of bacteria E.coli BL21 was carried out for validation as a model microorganism and results showed that detection was possible at 102 CFU/ml. The data acquired by spectrophotometric measurements were analyzed by ANN and bacteria classification with percentage error rates near 0% was achieved. The proposed LSPR-based, label-free sensor application proved that the developed methodology promises utile sensitivity enhancement potential for similar sensor platforms. © 2024 The Author(s)
  • Review
    Citation - WoS: 12
    Citation - Scopus: 11
    Engineering Periodontal Tissue Interfaces Using Multiphasic Scaffolds and Membranes for Guided Bone and Tissue Regeneration
    (Elsevier, 2024) Özkendir, Özge; Karaca, İlayda; Çullu, Selin; Yaşar, Hüsniye Nur,; Erdoğan, Oğulcan; Dikici, Serkan; Dikici, Betul Aldemir; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Periodontal diseases are one of the greatest healthcare burdens worldwide. The periodontal tissue compartment is an anatomical tissue interface formed from the periodontal ligament, gingiva, cementum, and bone. This multifaceted composition makes tissue engineering strategies challenging to develop due to the interface of hard and soft tissues requiring multiphase scaffolds to recreate the native tissue architecture. Multilayer constructs can better mimic tissue interfaces due to the individually tuneable layers. They have different characteristics in each layer, with modulation of mechanical properties, material type, porosity, pore size, morphology, degradation properties, and drug-releasing profile all possible. The greatest challenge of multilayer constructs is to mechanically integrate consecutive layers to avoid delamination, especially when using multiple manufacturing processes. Here, we review the development of multilayer scaffolds that aim to recapitulate native periodontal tissue interfaces in terms of physical, chemical, and biological characteristics. Important properties of multiphasic biodegradable scaffolds are highlighted and summarised, with design requirements, biomaterials, and fabrication methods, as well as post-treatment and drug/growth factor incorporation discussed.
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    3d Printing-Assisted Fabrication of Microfluidic Pneumatic Valves
    (IEEE, 2023) Keleş, Şeyda; Karakuzu, Betül; Tekin, Hüseyin Cumhur; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Pneumatic valves have a crucial place in the fluidic control in microfluidic systems. Pneumatic valves containing polydimethylsiloxane (PDMS) membrane structures are used in microfluidic systems such as cell separation, and cell manipulation due to their flexible structure, and ease of production. This study demonstrates the rapid and straightforward fabrication of pneumatic valve structures using PDMS membranes, achieved through the utilization of 3D-printed molds. As a result of our experiments, we observed valve closure in a fluidic channel with a height of 150 μm. This closure was achieved by utilizing 400 μm × 800 μm PDMS membrane with a thickness of 66 μm positioned between the fluidic and control channels, while applying 1.5 bar of pressure to the control channel. When the pressure is removed, the opening time of the valve is only 0.02 s, and this response time allows rapid valving function. The presented valve fabrication strategy would allow easy and low-cost production of sophisticated microfluidic chips. © 2023 IEEE.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots
    (Wiley, 2024) Yücel, Müge; Onbaş, Rabia; Arslan Yıldız, Ahu; Yıldız, Ümit Hakan; 04.01. Department of Chemistry; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
    This study describes the formation, size control, and penetration behavior of polymer nanodots (Pdots) consisting of single or few chain polythiophene-based conjugated polyelectrolytes (CPEs) via nanophase separation between good solvent and poor solvent of CPE. Though the chain singularity may be associated with dilution nanophase separation suggests that molecules of a good solvent create a thermodynamically driven solvation layer surrounding the CPEs and thereby separating the single chains even in their poor solvents. This statement is therefore corroborated with emission intensity/lifetime, particle size, and scattering intensity of polyelectrolyte in good and poor solvents. Regarding the augmented features, Pdots are implemented into cell imaging studies to understand the nuclear penetration and to differentiate the invasive characteristics of breast cancer cells. The python based red, green, blue (RGB) color analysis depicts that Pdots have more nuclear penetration ability in triple negative breast cancer cells due to the different nuclear morphology in shape and composition and Pdots have penetrated cell membrane as well as extracellular matrix in spheroid models. The current Pdot protocol and its utilization in cancer cell imaging are holding great promise for gene/drug delivery to target cancer cells by explicitly achieving the very first priority of nuclear intake. The penetration capability of cationic soft nanodots in to tumor models of breast cancer is demonstrated. The image analysis based on fluorescence intensity variation reveals the characteristics of translocation of nanodots in dense mediums such as tumor models.image
  • Article
    Anthraquinones and Macrocyclic Lactones From Endophytic Fungus Penicillium Roseopurpureum and Their Bioactivities
    (ACG Publications, 2024) Dizmen,B.; Üner,G.; Küçüksolak,M.; Gören,A.C.; Kırmızıbayrak,P.B.; Bedir,E.; 01. Izmir Institute of Technology
    Endophytic fungi colonize the internal and distinct tissues of the host plants. In recent years, there has been growing interest in endophytic fungi as valuable sources for drug discovery based on their rich metabolic profiles consisting of novel and bioactive compounds. Accordingly, our preliminary study demonstrated that an endophyte, namely Penicillium roseopurpureum isolated from Astragalus angustifolius, had high chemical diversity with an antiproliferative effect. Herein, fermentation of P. roseopurpureum resulted in the production of five new anthraquinone-type compounds (2, 4, 6, 7, 8) together with several known compounds [11-methoxycurvularin (1: epimeric mixture of 1a and 1b), carviolin (3), 11-hydroxycurvularin (5: diastereoisomeric mixture of 5a and 5b) and 1-O-methylemodin (9)]. The structures of the new compounds were established by NMR spectroscopy and HR-MS analysis. Cytotoxicity studies demonstrated that none of the compounds except for 1 and 5 had antiproliferative activity against prostate cancer cell lines. Interestingly, 1 was found as cytotoxic, whereas 5 exhibited cytostatic properties. Also, 7-AAD/Annexin V staining supported these results by showing that 1 caused cellular death, while 5 did not show any increase in dead cell content in comparison to the control. Lastly, cell cycle analysis showed that compounds had distinctive cell cycle arrest patterns. © 2024 ACG Publications.
  • Article
    Blank Frame and Intensity Variation Distortion Detection and Restoration Pipeline for Phase-Contrast Microscopy Time-Lapse Images
    (Aves, 2024) Ucar, Mahmut; Iheme, Leonardo O.; Onal, Sevgi; Pesen-Okvur, Devrim; Yalcin-Ozuysal, Ozden; Toreyin, Behcet U.; Unay, Devrim; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
    In this study, we propose a preprocessing pipeline for the detection and correction of distorted frames in time-lapse images obtained from phase-contrast microscopy. The proposed pipeline employs the average intensities of frames as a foundational element for the analysis. In order to evaluate the degree of correction required for intensity variance, a normalization technique is applied to the difference between the average intensity of a specific frame and the median average intensity of all frames within the study. Our restoration method increases the histogram similarity between the distorted and non-distorted frames, preserves trans-passing pixels in regions of interest, and mitigates the development of additional distortions. The efficacy of the proposed method was evaluated using 15 395 time-lapse image frames from 27 experiments using our own dataset and 830 time-lapse images from four different experiments obtained from the cell tracking challenge. The results of the validation demonstrate a high degree of numerical and visual accuracy of the proposed pipeline.
  • Article
    Citation - WoS: 11
    Citation - Scopus: 11
    Development of Tissue-Engineered Vascular Grafts From Decellularized Parsley Stems
    (Royal Society of Chemistry, 2023) Çevik, Merve; Dikici, Serkan; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Cardiovascular diseases are mostly associated with narrowing or blockage of blood vessels, and it is the most common cause of death worldwide. The use of vascular grafts is a promising approach to bypass or replace the blocked vessels for long-term treatment. Although autologous arteries or veins are the most preferred tissue sources for vascular bypass, the limited presence and poor quality of autologous vessels necessitate seeking alternative biomaterials. Recently, synthetic grafts have gained attention as an alternative to autologous grafts. However, the high failure rate of synthetic grafts has been reported primarily due to thrombosis, atherosclerosis, intimal hyperplasia, or infection. Thrombosis, the main reason for failure upon implantation, is associated with damage or absence of endothelial cell lining in the vascular graft's luminal surface. To overcome this, tissue-engineered vascular grafts (TEVGs) have come into prominence. Alongside the well-established scaffold manufacturing techniques, decellularized plant-based constructs have recently gained significant importance and are an emerging field in tissue engineering and regenerative medicine. Accordingly, in this study, we demonstrated the fabrication of tubular scaffolds from decellularized parsley stems and recellularized them with human endothelial cells to be used as a potential TEVG. Our results suggested that the native plant DNA was successfully removed, and soft tubular biomaterials were successfully manufactured via the chemical decellularization of the parsley stems. The decellularized parsley stems showed suitable mechanical and biological properties to be used as a TEVG material, and they provided a suitable environment for the culture of human endothelial cells to attach and create a pseudo endothelium prior to implantation. This study is the first one to demonstrate the potential of the parsley stems to be used as a potential TEVG biomaterial. © 2024 The Royal Society of Chemistry.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 4
    Biopatterning of 3d Cellular Model by Contactless Magnetic Manipulation for Cardiotoxicity Screening
    (Mary Ann Liebert, Inc, 2023) Önbaş, Rabia; Arslan Yıldız, Ahu; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Patterning cells to create three-dimensional (3D) cell culture models by magnetic manipulation is a promising technique, which is rapid, simple, and cost-effective. This study introduces a new biopatterning approach based on magnetic manipulation of cells with a bioink that consists alginate, cells, and magnetic nanoparticles. Plackett-Burman and Box-Behnken experimental design models were used to optimize bioink formulation where NIH-3T3 cells were utilized as a model cell line. The patterning capability was confirmed by light microscopy through 7 days culture time. Then, biopatterned 3D cardiac structures were formed using H9c2 cardiomyocyte cells. Cellular and extracellular components, F-actin and collagen Type I, and cardiac-specific biomarkers, Troponin T and MYH6, of biopatterned 3D cardiac structures were observed successfully. Moreover, Doxorubicin (DOX)-induced cardiotoxicity was investigated for developed 3D model, and IC50 value was calculated as 8.1 μM for biopatterned 3D cardiac structures, which showed higher resistance against DOX-exposure compared to conventional two-dimensional cell culture. Hereby, developed biopatterning methodology proved to be a simple and rapid approach to fabricate 3D cardiac models, especially for drug screening applications. Copyright 2023, Mary Ann Liebert, Inc., publishers.
  • Book Part
    Astragalus sp.
    (CRC Press, 2023) Yakuboğulları, Nilgün; Bedir, Erdal; 01.01. Units Affiliated to the Rectorate; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of Engineering
    Astragalus is one of the largest genera in Turkey and is widely distributed worldwide. The phytochemical studies on Turkish Astragalus species have presented 112 new compounds besides 63 known compounds. The overriding basis for biological activity studies is the traditional use of Astragalus roots in the Southeastern Region of Turkey to cure leukemia. As the isolated compounds did not show cytotoxic properties, a hypothesis that the biological activity of Astragalus saponins might result from the activation of the immune system came up. While Astragalus polysaccharides are used for their strong immunomodulatory activities in Chinese medicine, there are a few articles revealing the immunostimulatory properties of Astragalus saponins. Here, we summarized the compounds isolated from Turkish Astragalus species and concentrated on the immunomodulatory activities of these compounds to put forward their potential as saponin-based vaccine adjuvants. © 2024 selection and editorial matter, Ufuk Koca-Caliskan; individual chapters, the contributors.
  • Article
    Citation - WoS: 5
    Citation - Scopus: 7
    Ascorbic Acid Enhances the Metabolic Activity, Growth and Collagen Production of Human Dermal Fibroblasts Growing in Three-Dimensional (3D) Culture
    (Gazi Üniversitesi, 2023) Dikici, Serkan; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Tissue engineering (TE) enables the development of functional synthetic substitutes to be replaced with damaged tissues and organs instead of the use of auto or allografts. A wide range of biomaterials is currently in use as TE scaffolds. Among these materials, naturally sourced ones are favorable due to being highly biocompatible and supporting cell growth and function, whereas synthetic ones are advantageous because of the high tunability on mechanical and physical properties as well as being easy to process. Alongside the advantages of synthetic polymers, they mostly show hydrophobic behavior that limits biomaterial-cell interaction and, consequently, the functioning of the developed TE constructs. In this study, we assessed the impact of L-Ascorbic acid 2-phosphate (AA2P) on improving the culture conditions of human dermal fibroblasts (HDFs) growing on a three-dimensional (3D) scaffold made of polycaprolactone (PCL) using emulsion templating. Our results demonstrated that AA2P enhances the metabolic activity and growth of HDFs as well as collagen deposition by them when supplemented in their growth medium at 50 µg/mL concentration. It showed a great potential to be used as a growth medium supplement to circumvent the disadvantages of culturing human cells on a synthetic biomaterial that is not favored in default. AA2P's potential to improve cell growth and collagen deposition may prove an effective way to culture human cells on 3D PCL PolyHIPE scaffolds for various TE applications.
  • Article
    Citation - WoS: 15
    Citation - Scopus: 15
    Modifying Pickering Polymerized High Internal Phase Emulsion Morphology by Adjusting Particle Hydrophilicity
    (Elsevier, 2024) Durgut, Enes; Zhou, Muchu; Dikici, Betuel Aldemir; Foudazi, Reza; Claeyssens, Frederik; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    This study investigates the use of submicron polymeric particles with varying crosslinking densities as the sole stabilizer for producing Polymerized High Internal Phase Emulsions (PolyHIPE). We establish a direct correlation between the crosslinking density and the hydrophilicity of the polymer particles. The hydrophilicity of these particles significantly influences the morphology and rheology of HIPEs. These differences manifest as various morphological variations in the resulting PolyHIPE templates. It was discovered that by increasing the crosslinker weight percentage in the particles from 0 % to 100 %, PolyHIPEs with semi-open, open, and closed porous structures can be obtained. Furthermore, non-crosslinked particles were observed to dissolve in the continuous phase, acting as macromolecular surfactants that generate small pores akin to surfactant-stabilized structures in PolyHIPE. These findings offer fresh insights into the relationship between particle localization at the interface, HIPE rheology, and the formation of pore throats in Pickering PolyHIPEs, leading to the creation of either closed or open porous networks. Additionally, interfacial rheological results demonstrate that particles synthesized with varying monomer-to-crosslinker ratios exhibit different interfacial elasticities, which are linked to PolyHIPE morphology.
  • Review
    Citation - WoS: 22
    Citation - Scopus: 26
    Molecular Separation by Using Active and Passive Microfluidic Chip Designs: a Comprehensive Review
    (Wiley, 2023) Ebrahimi, Aliakbar; Didarian, Reza; Shih, Chih-Hsin; Nasseri, Behzad; Ethan Li, Yi-Chen; Shih, Steven; İçöz, Kutay; Tarım, Ergün Alperay; Akpek, Ali; Çeçen, Berivan; Bal Öztürk, Ayça; Güleç, Kadri; Tarım, Burcu Sırma; Tekin, Hüseyin Cumhur; 03.01. Department of Bioengineering; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Separation and identification of molecules and biomolecules such as nucleic acids, proteins, and polysaccharides from complex fluids are known to be important due to unmet needs in various applications. Generally, many different separation techniques, including chromatography, electrophoresis, and magnetophoresis, have been developed to identify the target molecules precisely. However, these techniques are expensive and time consuming. “Lab-on-a-chip” systems with low cost per device, quick analysis capabilities, and minimal sample consumption seem to be ideal candidates for separating particles, cells, blood samples, and molecules. From this perspective, different microfluidic-based techniques have been extensively developed in the past two decades to separate samples with different origins. In this review, “lab-on-a-chip” methods by passive, active, and hybrid approaches for the separation of biomolecules developed in the past decade are comprehensively discussed. Due to the wide variety in the field, it will be impossible to cover every facet of the subject. Therefore, this review paper covers passive and active methods generally used for biomolecule separation. Then, an investigation of the combined sophisticated methods is highlighted. The spotlight also will be shined on the elegance of separation successes in recent years, and the remainder of the article explores how these permit the development of novel techniques. © 2023 The Authors. Advanced Materials Interfaces published by Wiley-VCH GmbH.
  • Article
    Citation - Scopus: 7
    Μdacs 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 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 Technology
    Circulating 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 - WoS: 3
    Citation - Scopus: 5
    Microbial Desalination Cell Treated Spent Geothermal Brine as a Nutrient Medium in Hydroponic Lettuce Cultivation: Health Risk Assessment
    (Elsevier, 2024) Goren, A. Y.; Eskisoy, D. N.; Genisoglu, S.; Okten, H. E.; 03.07. Department of Environmental Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    The scarcity and contamination of freshwater resources are extremely critical issues today, and the expansion of water reuse has been considered as an option to decrease its impact. Therefore, the reuse of microbial desalination (MDC)-treated spent geothermal brine for agricultural purposes arises as a good solution to prevent water contamination and provide sustainable water usage. In this study, the potential of treated spent geothermal water from MDC system as a nutrient solution for the hydroponic cultivation of lettuce was evaluated. The effects of different water samples (Hoagland solution (R1) as a control, MDC-treated water (R2), 1:1, v/v mixture of MDCtreated water and Hoagland solution (R3), 4:1, v/v mixture of MDC-treated water and Hoagland solution (R4), and tap water (R5)) on lettuce growth were considered. The application of R3 and R4 samples for hydroponic lettuce cultivation was promising since the lettuce plants uptake sufficient nutrients for their growth and productivity with low toxic metal concentrations. In addition, the chlorophyll-a, chlorophyll-b, and carotene contents of lettuce were in the range of 1.045-2.391 mg/g, 0.761-1.986 mg/g, and 0.296-0.423 mg/g in different water samples, respectively. The content of chlorophyll-a was highest in R1 (2.391 mg/g), followed by R3 (2.371 mg/g). Furthermore, the health risk assessment of heavy metal accumulations in the lettuce plants cultivated in the various water samples was determined. Results showed that heavy metal exposure via lettuce consumption is unlikely to suffer noticeable adverse health problems with values below the permissible limit value.
  • Article
    Citation - WoS: 17
    Citation - Scopus: 15
    Antiproliferative and Apoptotic Effects of Olive Leaf Extract Microcapsules on Mcf-7 and A549 Cancer Cells
    (American Chemical Society, 2023) Bal, Yıldız; Sürmeli, Yusuf; Şanlı Mohamed, Gülşah; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Alginate microcapsules are a talented means for the delivery of broad curative biomacromolecules. In this study, we immobilized olive leaf extract (OLE) by calcium alginate (CA) and chitosan-coated CA (CCA) and characterized the OLE-loaded CA and CCA. The cytotoxic effect, the cell cycle arrest, and the apoptotic effect of OLE and its microcapsules were investigated against breast adenocarcinoma (MCF-7) and lung carcinoma (A549). As a result, the loading capacity of OLE-CA and OLE-CCA was found to be 80 and 99%, respectively, in optimal conditions. Also, OLE-CA and OLE-CCA were characterized by unique FTIR peaks and morphological display relative to the empty CCA microcapsules. The cytotoxicity analysis showed that the IC50 values of OLE-CA and OLE-CCA were determined to be 312 and 0.94 μg mL-1 against A549, respectively, whereas these were found to be 865.4 and 425.5 μg mL-1 for MCF-7 cells. On the other hand, the OLE microcapsules did not possess in any concentration of cytotoxic influence on the BEAS 2B healthy cell line. Also, the exposure of OLE-CCA to MCF-7 and A549 resulted in the arrest of more MCF-7 and A549 cells at the G0/G1 phase compared to the OLE. A549 and MCF-7 cells were predominantly found in the late apoptosis phase and necrosis phase, respectively. Optical microscopy images confirmed that OLE microcapsules were more effective against MCF-7 and A549 than free OLE. The present work suggested that the OLE microcapsules might be administered as nutrition supplements for cancer therapy. © 2023 The Authors. Published by American Chemical Society.