Bioengineering / Biyomühendislik

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

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  • 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.
  • 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.
  • 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.
  • 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.
  • Conference Object
    Citation - WoS: 12
    Citation - Scopus: 17
    Wearable Respiratory Rate Sensor Technology for Diagnosis of Sleep Apnea
    (IEEE, 2020) Cinel, Göktürk; Tarım, Ergün Alperay; Tekin, Hüseyin Cumhur
    Sleep apnea is a disease that occurs during sleep, which affects the daily life of patients due to the obstruction of the upper respiratory tract and decreases oxygen level in blood and it may even lead to patient death in the later stage. Monitoring the patients regularly has absolute importance to prevent patient disorders caused by sleep apnea. Wearable sensor technologies and patient tracking systems provide diagnosis, treatment, and monitoring of patients, and procure better health services in medical fields. In addition to decreasing the workload of health institutions, remote patient monitoring systems can serve continuous monitoring and determine variable symptoms of the patients. In this paper, we propose a patient monitoring system, which will be used for diagnosis and monitoring of sleep apnea by tracking the respiratory rate of patients with wearable sensor technology. The respiratory rate is detected using either an accelerometer sensor to be placed on the patients' abdomen or a temperature sensor to be placed on their noses. The proposed system offers an increase in the versatility of patient monitoring systems and offers an alternative new technology in sleep apnea diagnosis.
  • Conference Object
    Citation - WoS: 2
    Citation - Scopus: 2
    Portatif ve Düşük Maliyetli Merceksiz Holografik Mikroskop Platformu ile Nanoparçacık Tespiti
    (IEEE, 2020) Delikoyun, Kerem; Keçili, Seren; Tekin, Hüseyin Cumhur
    In the biological and medical science, detection of biomolecule at very low concentration (<100 pg/mL) is of great importance and it is extensively used in the diagnosis of diseases, drug response monitoring and cancer research. For biomolecule detection tests, captured biomolecules generate signals (fluorescence, color, etc.), which are analyzed by trained personnel in bulky, high cost and fragile devices. However, for clinical applications, the access to these tests is very difficult at resource-limited settings. Lensless holographic microscopy provides high resolution imaging of samples without the need of expensive and fragile optical elements (mirror, lens, filter, etc.) used in traditional imaging technologies. While this technology offers a robust, portable and low-cost design, it enables fully automated processing of the sample image with digital processing schemes and this can also help eliminate user error. In this study, lensless holographic microscopy platform, which can be used in surface coverage assays for the detection of biomolecules, is proposed. It has been shown that nanoparticles (700-1200 nm) used as labels in surface coverage assays for the detection of biomolecules could be sensed on the platform. Therefore, it is anticipated that biomolecules detection could be realized rapidly and sensitively with this easy-to-use and low-cost imaging platform at the location where the high-level health institutions are not available and even at point-of-care settings.
  • Conference Object
    Citation - WoS: 1
    Citation - Scopus: 2
    A Vacuum-Integrated Centrifugal Microfluidic Chip for Density-Based Separation of Microparticles
    (IEEE, 2021) Öksüz, Cemre; Tekin, Hüseyin Cumhur
    Here we present a new vacuum-integrated centrifugal microfluidic chip for the density-based separation of microparticles. A sample was loaded in a fluidic channel using the gas permeability feature of polydimethylsiloxane (PDMS) membrane between fluidic and control channels. Vacutun was applied from control channel to drive a density media and then the sample containing microparticles in the dead-end fluidic channel. Afterwards, the chip was disconnected from the vacuum and it was centrifugated. If the sample contains microparticles denser than the density media, the microparticles are sedimented at the end of the microfluidic channel so that these particles can be separated from remaining the lower density particles. With this approach, we separated 1.09 g/mL microparticles with 82,6% efficiency and 99% purity from 1.02 g/mL microparticles. Separated particles in the microfluidic chip can also be inspected under a microscope for further analysis. This simple approach offers high efficient density-based separation of microparticles with close densities.
  • Article
    Citation - WoS: 22
    Citation - Scopus: 26
    Magnetic Levitation Assisted Biofabrication, Culture, and Manipulation of 3d Cellular Structures Using a Ring Magnet Based Setup
    (Wiley, 2021) Anıl İnevi, Müge; Delikoyun, Kerem; Meşe Özçivici, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, Engin
    Diamagnetic levitation is an emerging technology for remote manipulation of cells in cell and tissue level applications. Low-cost magnetic levitation configurations using permanent magnets are commonly composed of a culture chamber physically sandwiched between two block magnets that limit working volume and applicability. This work describes a single ring magnet-based magnetic levitation system to eliminate physical limitations for biofabrication. Developed configuration utilizes sample culture volume for construct size manipulation and long-term maintenance. Furthermore, our configuration enables convenient transfer of liquid or solid phases during the levitation. Before biofabrication, we first calibrated/ the platform for levitation with polymeric beads, considering the single cell density range of viable cells. By taking advantage of magnetic focusing and cellular self-assembly, millimeter-sized 3D structures were formed and maintained in the system allowing easy and on-site intervention in cell culture with an open operational space. We demonstrated that the levitation protocol could be adapted for levitation of various cell types (i.e., stem cell, adipocyte and cancer cell) representing cells of different densities by modifying the paramagnetic ion concentration that could be also reduced by manipulating the density of the medium. This technique allowed the manipulation and merging of separately formed 3D biological units, as well as the hybrid biofabrication with biopolymers. In conclusion, we believe that this platform will serve as an important tool in broad fields such as bottom-up tissue engineering, drug discovery and developmental biology.