Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Conference Paper 3d Printing-Assisted Fabrication of Microfluidic Pneumatic Valves(IEEE, 2023) Keleş, Şeyda; Karakuzu, Betül; Tekin, Hüseyin CumhurPneumatic 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.Review Citation - WoS: 30Citation - Scopus: 33Molecular 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 CumhurSeparation 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.Review Citation - WoS: 23Citation - Scopus: 24Microfluidic-Based Technologies for Diagnosis, Prevention, and Treatment of Covid-19: Recent Advances and Future Directions(Springer, 2023) Tarım, Ergün Alperay; Anıl İnevi, Müge; Özkan, İlayda; Keçili, Seren; Bilgi, Eyüp; Başlar, Muhammet Semih; Özçivici, Engin; Öksel Karakuş, Ceyda; Tekin, Hüseyin CumhurThe COVID-19 pandemic has posed significant challenges to existing healthcare systems around the world. The urgent need for the development of diagnostic and therapeutic strategies for COVID-19 has boomed the demand for new technologies that can improve current healthcare approaches, moving towards more advanced, digitalized, personalized, and patient-oriented systems. Microfluidic-based technologies involve the miniaturization of large-scale devices and laboratory-based procedures, enabling complex chemical and biological operations that are conventionally performed at the macro-scale to be carried out on the microscale or less. The advantages microfluidic systems offer such as rapid, low-cost, accurate, and on-site solutions make these tools extremely useful and effective in the fight against COVID-19. In particular, microfluidic-assisted systems are of great interest in different COVID-19-related domains, varying from direct and indirect detection of COVID-19 infections to drug and vaccine discovery and their targeted delivery. Here, we review recent advances in the use of microfluidic platforms to diagnose, treat or prevent COVID-19. We start by summarizing recent microfluidic-based diagnostic solutions applicable to COVID-19. We then highlight the key roles microfluidics play in developing COVID-19 vaccines and testing how vaccine candidates perform, with a focus on RNA-delivery technologies and nano-carriers. Next, microfluidic-based efforts devoted to assessing the efficacy of potential COVID-19 drugs, either repurposed or new, and their targeted delivery to infected sites are summarized. We conclude by providing future perspectives and research directions that are critical to effectively prevent or respond to future pandemics.Article Citation - WoS: 9Citation - Scopus: 9Fabrication 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, AhuPaper-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.Article Citation - WoS: 8Citation - Scopus: 11Cost-Effective and Rapid Prototyping of Pmma Microfluidic Device Via Polymer-Assisted Bonding(Springer, 2021) Sözmen, Alper Baran; Arslan Yıldız, AhuMicrofluidic systems are relatively new technology field with a constant need of novel and practical manufacturing materials and methods. One of the main shortcomings of current methods is the inability to provide rapid bonding, with high bonding strength, and sound microchannel integrity. Herein we propose a novel method of assembly that overcomes the mentioned limitations. Polymer-assisted bonding is a novel, rapid, simple, and inexpensive method where a polymer is solubilized in a solvent and the constituted solution is used as a bonding agent. In this study, we combined this method with utilization of several phase-changing materials (PCMs) as channel-protective agents. Glauber's salt appeared to be more suitable as a channel-protective agent compared to rest of the salts that have been used in this study. Based on the bonding strength, quality analyses, leakage tests, and SEM imaging, the superior assisting bonding solvent was determined to be dichloromethane with a PMMA concentration of 2.5% (W/V). It showed a bonding strength of 23.794 MPa and a nearly non-visible bonding layer formation of 2.83 mu m in width which is proved by SEM imaging. The said combination of PCM, solvent, and polymer concentration also showed success in leakage tests and an application of micro-droplet generator fabrication. The application was carried out to test the applicability of developed prototyping methodology, which resulted in conclusive outcomes as the droplet generator simulation run in COMSOL Multiphysics version 5.1 software. In conclusion, the developed fabrication method promises simple, rapid, and strong bonding with sharp and clear micro-channel engraving.Article Citation - WoS: 5Citation - Scopus: 4Monitoring Neutropenia for Cancer Patients at the Point of Care(Wiley, 2017) İnan, Hakan; Kingsley, James L.; Özen, Mehmet O.; Tekin, Hüseyin Cumhur; Hoerner, Christian R.; Imae, Yoriko; Demirci, UtkanNeutrophils have a critical role in regulating the immune system. The immune system is compromised during chemotherapy, increasing infection risks and imposing a need for regular monitoring of neutrophil counts. Although commercial hematology analyzers are currently used in clinical practice for neutrophil counts, they are only available in clinics and hospitals, use large blood volumes, and are not available at the point of care (POC). Additionally, phlebotomy and blood processing require trained personnel, where patients are often admitted to hospitals when the infections are at late stage due to lack of frequent monitoring. Here, a reliable method is presented that selectively captures and quantifies white blood cells (WBCs) and neutrophils from a finger prick volume of whole blood by integrating microfluidics with high-resolution imaging algorithms. The platform is compact, portable, and easy to use. It captures and quantifies WBCs and neutrophils with high efficiency (> 95%) and specificity (> 95%) with an overall 4.2% bias compared to standard testing. The results from a small cohort of patients (N = 11 healthy, N = 5 lung and kidney cancer) present a unique disposable cell counter, demonstrating the ability of this tool to monitor neutrophil and WBC counts within clinical or in resource-constrained environments.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.
