Bioengineering / Biyomühendislik

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

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Access Right: Open AccessAuthor: search.filters.author.Tekin, Hüseyin Cumhur

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  • Conference Paper
    3d Printing-Assisted Fabrication of Microfluidic Pneumatic Valves
    (IEEE, 2023) Keleş, Şeyda; Karakuzu, Betül; Tekin, Hüseyin Cumhur
    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.
  • Review
    Citation - WoS: 30
    Citation - Scopus: 33
    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
    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: 11
    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
    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)
  • Review
    Citation - WoS: 23
    Citation - Scopus: 24
    Microfluidic-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 Cumhur
    The 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.
  • Research Project
    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.
  • Article
    Citation - WoS: 15
    Citation - Scopus: 16
    Electromechanical Rt-Lamp Device for Portable Sars-Cov Detection
    (Elsevier, 2023) Tarım, Ergün Alperay; Öksüz, Cemre; Karakuzu, Betül; Appak, Özgür; Sayıner, Ayça Arzu; Tekin, Hüseyin Cumhur
    Rapid point-of-care tests for infectious diseases are essential, especially in pandemic conditions. We have developed a point-of-care electromechanical device to detect SARS-CoV-2 viral RNA using the reverse-transcription loop-mediated isothermal amplification (RT-LAMP) principle. The developed device can detect SARS-CoV-2 viral RNA down to 103 copies/mL and from a low amount of sample volumes (2 μL) in less than an hour of standalone operation without the need for professional labor and equipment. Integrated Peltier elements in the device keep the sample at a constant temperature, and an integrated camera allows automated monitoring of LAMP reaction in a stirring sample by using colorimetric analysis of unfocused sample images in the hue/saturation/value color space. This palm-fitting, portable and low-cost device does not require a fully focused sample image for analysis, and the operation could be stopped automatically through image analysis when the positive test results are obtained. Hence, viral infections can be detected with the portable device produced without the need for long, expensive, and labor-intensive tests and equipment, which can make the viral tests disseminated at the point-of-care.
  • Conference Object
    Size-Based Microparticle Seperation Using Negative Magnetophoresis
    (Chemical and Biological Microsystems Society, 2021) Solmaz Özçelik, Özge; Öksüz, Cemre; Tekin, Hüseyin Cumhur
    We present a new size-based microparticle separation device using negative magnetophoresis. Microparticles spiked in the paramagnetic medium were filtered with respect to their sizes in a microfluidic channel placed between two magnets. Negative magnetophoresis allows large microparticles to be captured before the magnets, while small microparticles pass through the magnets under a constant flow. With this method, we reached 84.2% capturing efficiency of large microparticles (44 µm diameter) and capturing purity of 80.3% in the presence of small microparticles (17 µm diameter) at 3 µL/min flow rate. The capturing purity could further improve up to 99% by increasing the flow rate.
  • Article
    Citation - WoS: 10
    Citation - Scopus: 14
    An Electromechanical Lab-On Platform for Colorimetric Detection of Serum Creatinine
    (American Chemical Society, 2022) Karakuzu, Betül; Tarım, Ergün Alperay; Öksüz, Cemre; Tekin, Hüseyin Cumhur
    Chronic kidney disease (CKD) is a high-cost disease that affects approximately one in ten people globally, progresses rapidly, results in kidney failure or dialysis, and triggers other diseases. Although clinically used serum creatinine tests are used to evaluate kidney functions, these tests are not suitable for frequent and regular control at-home settings that obstruct the regular monitoring of kidney functions, improving CKD management with early intervention. This study introduced a new electromechanical lab-on-a-chip platform for point-of-care detection of serum creatinine levels using colorimetric enzyme-linked immunosorbent assay (ELISA). The platform was composed of a chip containing microreservoirs, a stirring bar coated with creatinine-specific antibodies, and a phone to detect color generated via ELISA protocols to evaluate creatinine levels. An electromechanical system was used to move the stirring bar to different microreservoirs and stir it inside them to capture and detect serum creatinine in the sample. The presented platform allowed automated analysis of creatinine in ~50 min down to ~1 and ~2 mg/dL in phosphate-buffered saline (PBS) and fetal bovine serum (FBS), respectively. Phone camera measurements in hue, saturation, value (HSV) space showed sensitive analysis compared to a benchtop spectrophotometer that could allow low-cost analysis at point-of-care.
  • Article
    Citation - WoS: 37
    Citation - Scopus: 48
    Microfluidic-Based Virus Detection Methods for Respiratory Diseases
    (Springernature, 2021) Tarım, Ergün Alperay; Karakuzu, Betül; Öksüz, Cemre; Sarıgil, Öykü; Kızılkaya, Melike; Al-Ruweidi, Mahmoud Khatib A. A.; Yalçın, Hüseyin Çağatay; Özçivici, Engin; Tekin, Hüseyin Cumhur
    With the recent SARS-CoV-2 outbreak, the importance of rapid and direct detection of respiratory disease viruses has been well recognized. The detection of these viruses with novel technologies is vital in timely prevention and treatment strategies for epidemics and pandemics. Respiratory viruses can be detected from saliva, swab samples, nasal fluid, and blood, and collected samples can be analyzed by various techniques. Conventional methods for virus detection are based on techniques relying on cell culture, antigen-antibody interactions, and nucleic acids. However, these methods require trained personnel as well as expensive equipment. Microfluidic technologies, on the other hand, are one of the most accurate and specific methods to directly detect respiratory tract viruses. During viral infections, the production of detectable amounts of relevant antibodies takes a few days to weeks, hampering the aim of prevention. Alternatively, nucleic acid-based methods can directly detect the virus-specific RNA or DNA region, even before the immune response. There are numerous methods to detect respiratory viruses, but direct detection techniques have higher specificity and sensitivity than other techniques. This review aims to summarize the methods and technologies developed for microfluidic-based direct detection of viruses that cause respiratory infection using different detection techniques. Microfluidics enables the use of minimal sample volumes and thereby leading to a time, cost, and labor effective operation. Microfluidic-based detection technologies provide affordable, portable, rapid, and sensitive analysis of intact virus or virus genetic material, which is very important in pandemic and epidemic events to control outbreaks with an effective diagnosis.
  • Conference Object
    Citation - Scopus: 1
    Magnetic 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. Cumhur
    Magnetic 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.