Bioengineering / Biyomühendislik

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

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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
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)
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
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
Biopatterning of 3d Cellular Structures Via Contactless Magnetic Manipulation for Drug Screening
(Mary Ann Liebert, 2023) Önbaş, Rabia; Arslan Yıldız, Ahu
"Patterning and manipulation techniques have been used to fabricate 3D cell cultures in tissue engineering. The contactless magnetic manipulation approach is a rapid, simple, and cost-effective method that requires paramagnetic agents [1-3] or magnetic materials [4]. Here, to obtain patterned 3D cellular structures a new alginate-based bio-ink formulation was developed to fabricate 3D cellular structures using contactless magnetic manipulation. 3D cardiac model was obtained by patterning rat cardiomyocytes. Cellular and extracellular components and cardiac-specific markers of patterned 3D cellular structures were indicated successfully. Drug response of patterned 3D cellular structures was evaluated by applying doxorubicin. Patterned 3D cardiac cellular structures showed significantly different drug response compared to conventional 2D cell cultures. In conclusion, this technique provides an easy, efficient, and low-cost methodology to fabricate 3D cardiac structures for drug screening.
Citation - WoS: 9
Citation - Scopus: 9
Fabrication and Development of a Microfluidic Paper-Based Immunosorbent Assay Platform (μpisa) for Colorimetric Detection of Hepatitis C
(Royal Society of Chemistry, 2023) Özefe, Fatih; Arslan Yıldız, Ahu
Paper-based microfluidics is an emerging analysis tool used in various applications, especially in point-of-care (PoC) diagnostic applications, due to its advantages over other types of microfluidic devices in terms of simplicity in both production and operation, cost-effectiveness, rapid response time, low sample consumption, biocompatibility, and ease of disposal. Recently, various techniques have been developed and utilized for the fabrication of paper-based microfluidics, such as photolithography, micro-embossing, wax and PDMS printing, etc. In this study, we offer a fabrication methodology for a microfluidic paper-based immunosorbent assay (μPISA) platform and the detection of Hepatitis C Virus (HCV) was carried out to validate this platform. A laser ablation technique was utilized to form hydrophobic barriers easily and rapidly, which was the major advantage of the developed fabrication methodology. The characterization of the μPISA platform was performed in terms of micro-channel properties using bright-field (BF) microscopy, and surface properties using scanning electron microscopy (SEM). At the same time, sample volume and liquid handling capacity were analyzed quantitatively. Ablation speed (S) and laser power (P) were optimized, and it was shown that one combination (10P60S) provided minimal deviation in micro-channel dimensions and prevented deterioration of hydrophobic barriers. Also, the minimum hydrophobic barrier width, which prevents cross-barrier bleeding, was determined to be 255.92 ± 10.01 μm. Furthermore, colorimetric HCV NS3 detection was implemented to optimize and validate the μPISA platform. Here, HCV NS3 in both PBS and human blood plasma was successfully detected by the naked eye at concentrations as low as 1 ng mL−1 and 10 ng mL−1, respectively. Moreover, the limit of detection (LoD) values for HCV NS3 were acquired as 0.796 ng mL−1 in PBS and 2.203 ng mL−1 in human blood plasma with a turnaround time of 90 min. In comparison with conventional ELISA, highly sensitive and rapid HCV NS3 detection was accomplished colorimetrically on the developed μPISA platform.
Manyetik levitasyon yöntemiyle kemik hücrelerinin ağırlıksız ortamda kültürlenmesi
(2019) Tekin, Hüseyin Cumhur; Arslan Yıldız, Ahu; Özçivici, Engin
Mekanik kuvvetler canlılarda özellikle kas ve kemik dokularının sağlıklı formlarda bulunmasında ve fonksiyonlarını yerine getirmesinde önemli rol oynarlar. Mekanik kuvvetlerin kısmen ya da tamamen ortadan kalktığı felç, yatalaklık, yaşlılık ve yerçekimsiz ortam koşulları kas ve kemik dokusunda ciddi miktarda kayıplar meydana getirmektedir. Kemik doku kayıplarına ek olarak mekanik yüklenmenin ortadan kalkması kemik iliğinde bulunan ve kemik hücre havuzunu oluşturan mezenkimal kök hücrelerin yağ yönelimine girmelerine ve kemik iliğinin aşırı miktarda yağlanmasına sebep olur. Bu durum kemiklerde kırılma riskini arttırır. Ayrıca yağ yönelimine bir kez giren kök hücreler kronik olarak tekrar kemik oluşturmaya, dolayısıyla rejenerasyona kolayca yönelemezler. Yaşam koşulları ya da ilerleyen yaş sebebiyle bir insanın kemik kütlesini kaybedip yağ kütlesi kazanmasının birey ve toplum için ciddi bir sosyo-ekonomik maliyeti vardır. Modern toplumda yaş ortalaması artıp hareket ihtiyacı azalırken, kemik erimesi (osteoporoz) ve şişmanlık (obezite) oranlarında da bir artış görülmekte ve bu hastalıkların tedavisi için gereken maddi kaynaklar toplum refahını kısıtlamaktadır. Bu durumla mücadele edebilmek için tedaviye yönelik biyomedikal yaklaşımların geliştirilmesi gerekmektedir. Mekanik kuvvet yoksunluğu ile kemik erimesinin arasındaki ilişkinin incelenmesi için günümüzde gönüllü yatalaklık, fiziksel sınırlama ve kasılmayı önleyici ajanların kullanılması gibi yöntemler tercih edilmektedir. Ancak bu teknikler uygulama zorluğu ve barındırdığı etik problemler dolayısı ile verimli olarak kullanılamamaktadır. Bunun yanı sıra da hücre bazındaki mekanik kuvvet yoksunluğu veya ağırlıksız ortam çalışmaları pahalı uzay uçuşları veya biyoreaktör sistemlerine olan gereksinimden dolayı detaylı olarak gerçekleştirilememektedir. Son yıllarda temel amacı hücre ayrıştırma olarak geliştirilen manyetik levitasyon tekniği kemik hücrelerinin ağırlıksız ortamda incelenebilmesi için oldukça önemli bir fırsat yaratmıştır. Bu projenin amacı manyetik levitasyon prensibini kullanarak kemik ve kemik iliği hücrelerini ağırlıksız ortamda kültürleyerek, oluşan moleküler ve hücresel değişimleri kısa ve uzun vadeli olarak incelemektir. Bu amaca ulaşmak için hücre kültürü sırasında besiyeri ortamı Gadolinyum iyonları kullanılarak paramanyetik hale getirilmiş ve hücreler iki adet neodymium mıknatısın yaratacağı manyetik ortamda ağırlık vektörleri sıfırlanmış şekilde asılı kalmıştır. Projenin sonuçlanması ile manyetik levitasyon tekniği ile ağırlıksız ortamda kemik hücre kültürü teknolojisi geliştirilmiş olacak, ayrıca kemik hücrelerinin ağırlıksız ortamda verdikleri hücresel ve moleküler yanıtların kolay ve ucuz bir şekilde incelenmesi sağlanmıştır.
Citation - WoS: 17
Citation - Scopus: 18
Development of a Hydrocolloid Bio-Ink for 3d Bioprinting
(Royal Society of Chemistry, 2022) Yıldırım, Özüm; Arslan Yıldız, Ahu
A new generation of bio-inks that are soft, viscous enough, stable in cell culture, and printable at low printing pressures is required in the current state of 3D bioprinting technology. Hydrogels can meet these features and can mimic the microenvironment of soft tissues easily. Hydrocolloids are a group of hydrogels which have a suitable gelling capacity and rheological properties. According to the literature, polysaccharide-based hydrocolloids are used in the food industry, wound healing technologies, and tissue engineering. Quince seed hydrocolloids (QSHs), which consist of mostly glucuronoxylan, can easily be obtained from quince seeds by water extraction. In this study, the use of a QSH as a bio-ink was investigated. The suitability of QSH for the printing process was assessed by rheological, uniformity and pore factor analyses. Appropriate printing parameters were determined and the characterization of the bioprinted QSHs was performed by SEM analysis, water uptake capacity measurement, and protein adsorption assay. The bioprinted QSHs had excellent water uptake capacity and showed suitable protein adsorption behaviour. Analyses of the biocompatibility and cellular viability of bioprinted QSHs were conducted using NIH-3T3 fibroblast cells and the results were found to be high during short and long-term cell culture periods. It was proved that QSH is a highly promising bio-ink for 3D bioprinting and further tissue engineering applications.
On-Chip 3d Cell Culture Platform for Tumor Modeling and Drug Screening
(Mary Ann Liebert, 2022) Yıldırım, Özüm; Arslan Yıldız, Ahu
Three-dimensional (3D) cell culture allows cell-cell and cellmatrix interactions and provides more in vivo like models rather than 2D cell culture which cannot fully mimic native tissue. 3D cell culture on microfluidics allows formation of 3D structures that mimic the physiological and chemical microenvironment for cells[1]. These microfluidic platforms also downsize bench-top laboratory to a microchip, require miniaturized reagent, and are convenient for dynamic drug screening[2]. In this study, a microfluidic platform was designed which is housing a PLLCL scaffold fabricated by electrospinning methodology.
Biofabrication by Magnetic Levitational Assembly of Cells Into Defined 3d Cellular Structures
(Mary Ann Liebert, 2022) Arslan Yıldız, Ahu
In 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.
Development of New Generation Hydrocolloid Bio-Ink for 3d Bioprinting
(Mary Ann Liebert, 2022) Arslan Yıldız, Ahu
Bioprinting enables the production of 3-dimensional (3D) structures by combining bioinks, living cells, extracellular matrix (ECM) components, biochemical factors, proteins, drugs; and it has recently become one of the most promising techniques in the field of tissue engineering. The successful production of the 3D structure to be created by 3D bioprinting technology depends on the properties of the bio-ink to be used. Hydrogel/hydrocolloid materials used as bio-inks are developed using synthetic and natural polymers where they have the necessary rheological properties for printing, they also have biocompatibility, low toxicity and support for cell attachment. Natural hydrogels, which have the ability to mimic the extracellular matrix structure and function at a high rate, are highly preferred bioink materials for bioprinting applications.
Development of 3d Cardiac Models Via Magnetic Manipulation for Drug Screening Studies
(Mary Ann Liebert, 2022) Önbaş, Rabia; Arslan Yıldız, Ahu
Drug discovery and development process comprise of preclinical and clinical phases that are very intensive, long, and expensive research phases. However, drug candidates can fail in clinical trials. Toxicity is the major reason that leads to about 30% of drug development failures. Recently, the withdrawal rate of drugs from the market was increased to 33.3%from5.1%due to cardiotoxicity. When the drug fails at phase I, the reasons are probably related to 2-dimensional (2D) cell culture studies that do not represent the real tissue physiology; therefore, they provide misdirected data about the efficacy and toxicity of drug.

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