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Browsing by Author "Icoz, Kutay"

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    Article
    Ball Lens Based Mobile Microscope
    (GAZI UNIVCENTER CAMPUS TECHNOLOGY FAC B BLOCK EK BINA, 2ND FL, ANKARA, 06500, TURKEY, 2016) Icoz, Kutay; 0000-0002-0947-6166; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü; Icoz, Kutay
    In this paper we report a low cost, simple and mobile microscope based on attachment of a ball lens to a cell phone. The system's noise and parameters affecting the image quality is investigated. The ball lens provides approximately 100X magnification and together with the cell phone's integrated lens and image sensor, 3,4-micron resolution is reached. The field-of-view of the system is 1500x1500 mu m where the price of the ball lens and the holder is less than 10 cents. By using this system as an optical light microscope, we are able to acquire images of micro particles and micro sensors. When combined with image processing methods, this optical system is capable of doing complex analysis as an alternative to commercial optical light microscopes.
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    Article
    Capturing B type acute lymphoblastic leukemia cells using two types of antibodies
    (WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2019) Icoz, Kutay; Gercek, Tayyibe; Murat, Aysegul; Ozcan, Servet; Unal, Ekrem; AGÜ, Mühendislik Fakültesi, Elektrik & Elektronik Mühendisliği Bölümü;
    One way to monitor minimal residual disease (MRD) is to screen cells for multiple surface markers using flow cytometry. In order to develop an alternative microfluidic based method, isolation of B type acute lymphoblastic cells using two types of antibodies should be investigated. The immunomagnetic beads coated with various antibodies are used to capture the B type acute lymphoblastic cells. Single beads, two types of beads and surface immobilized antibody were used to measure the capture efficiency. Both micro and nanosize immunomagnetic beads can be used to capture B type acute lymphoblastic cells with a minimum efficiency of 94% and maximum efficiency of 98%. Development of a microfluidic based biochip incorporating immunomagnetic beads and surface immobilized antibodies for monitoring MRD can be an alternative to current cost and time inefficient laboratory methods. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2737, 2019
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    Deep learning based semantic segmentation and quantification for MRD biochip images
    (ELSEVIER SCI LTD, 2022) Çelebi, Fatma; Tasdemir, Kasim; Icoz, Kutay; 0000-0002-0947-6166; AGÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümü; Çelebi, Fatma; Tasdemir, Kasim; Icoz, Kutay
    Microfluidic platforms offer prominent advantages for the early detection of cancer and monitoring the patient response to therapy. Numerous microfluidic platforms have been developed for capturing and quantifying the tumor cells integrating several readout methods. Earlier, we have developed a microfluidic platform (MRD Biochip) to capture and quantify leukemia cells. This is the first study which employs a deep learning-based segmentation to the MRD Biochip images consisting of leukemic cells, immunomagnetic beads and micropads. Implementing deep learning algorithms has two main contributions; firstly, the quantification performance of the readout method is improved for the unbalanced dataset. Secondly, unlike the previous classical computer visionbased method, it does not require any manual tuning of the parameters which resulted in a more generalized model against variations of objects in the image in terms of size, color, and noise. As a result of these benefits, the proposed system is promising for providing real time analysis for microfluidic systems. Moreover, we compare different deep learning based semantic segmentation algorithms on the image dataset which are acquired from the real patient samples using a bright-field microscopy. Without cell staining, hyper-parameter optimized, and modified U-Net semantic segmentation algorithm yields 98.7% global accuracy, 86.1% mean IoU, 92.2% mean precision, 92.2% mean recall and 92.2% mean F-1 score measure on the patient dataset. After segmentation, quantification result yields 89% average precision, 97% average recall on test images. By applying the deep learning algorithms, we are able to improve our previous results that employed conventional computer vision methods.
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    Design, modeling, and control of a horizontal magnetic micromanipulator
    (SAGE PUBLICATIONS LTD, 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2019) Ablay, Gunyaz; Boyuk, Mustafa; Icoz, Kutay; 0000-0002-0947-6166; 0000-0003-2862-6761; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü
    Magnetic micromanipulators with a wide range of force generating capabilities are able to manipulate micron size particles for various applications and measurements. These magnetic particles can be coated with receptors to specifically bind to target biomolecules. In this work, a horizontal magnetic micromanipulator is designed, modeled and controlled for single micron size magnetic particle manipulations. A method is presented for dynamic modeling of magnetic micromanipulators. A feedback control method is designed that allows direct linearization of the system. It is shown that the proposed controller guarantees the stability of the closed-loop system, and yields zero steady-state error in a wide range of operation conditions. We show that the micromanipulator is able to generate a wide range of piconewton (pN) scale forces on a superparamagnetic particle for single molecule separation, and biosensor developments.
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    Detection of Proteins Using Nano Magnetic Particle Accumulation-Based Signal Amplification
    (MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2016) Icoz, Kutay; Mzava, Omary; AGÜ, Mühendislik Fakültesi, Elektrik & Elektronik Mühendisliği Bölümü;
    We report a biosensing method based on magnetic particles where coated magnetic particles are used for immunomagnetic separation, and uncoated magnetic particles are used for signal enhancement. To quantify the signal amplification, optical micrographs are analyzed to measure changes in pixel area and pixel intensity. Microcontact-printed surface receptors are arranged in alternating lines on gold chips, enabling differential calculations. In a model experiment, target molecules-streptavidin-are first captured and separated by biotin-coated magnetic particles, and then exposed to a gold surface functionalized with biotin-coupled bovine serum albumin, forming a sandwich assay. Applying a magnetic field and introducing uncoated magnetic particles resulted in accumulation around magnetic particles in the sandwich assay and enhancement of the contrast to noise ratio at least by eight-fold in a range of 0.1-100 mu M.
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    Feedback controller designs for an electromagnetic micromanipulator
    (SAGE PUBLICATIONS LTD, 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2019) Boyuk, Mustafa; Eroglu, Yakup; Ablay, Gunyaz; Icoz, Kutay; 0000-0002-0947-6166; 0000-0003-2862-6761; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü
    Magnetic micromanipulators are capable of generating wide range of magnetic forces to manipulate magnetic microparticles for biomedical applications. In this study, a multipole magnetic micromanipulator system including electromagnets, driver circuitry and control unit is designed, modeled and implemented. The micromanipulator can produce a broad range of magnetic forces up to 25 pN on a single magnetic microparticle (1-10 mu m diameter) that is 5 mm away from the electromagnet core tip. Both linear and nonlinear controllers are designed and implemented, and the proposed nonlinear controller produces smooth control currents to assure closed-loop stability of the system with 1 s non-overshoot transient response and zero steady-state tracking error. The maximum output current of the driver circuitry is set to 1 A. The single particle at the center is moved at a speed of 5 mm/s. The fully automatic system can be utilized in applications related to single cell or microparticle manipulations.
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    Article
    High spatial resolution IoT based air PM measurement system
    (SPRINGERVAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS, 2021) Icoz, Ebru; Malik, Fasih M.; Icoz, Kutay; 0000-0002-0947-6166; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü; Icoz, Ebru; Malik, Fasih M.; Icoz, Kutay
    Air pollution is one of the global problems of the current era. According to World Health Organization more than 80% of the people living in metropolitan areas breathe air which exceeds the guideline limits. Particulate matter, the mixture of liquid and solid particles having diameters less than 10 mu m, is one of the important pollutants in the air. The main source of the Particulate matter is mostly burning reactions associated with industry, vehicles and homes. Several studies have shown the lethal impact of particulate matter to public health and environment. The rise of particulate matter amount in air has been linked to several health problems such as not only respiratory diseases but also mortality in infants and heart attacks. Currently, bulky stations which are high-cost and have limited spatial resolution are used to monitor the air quality. In this study we developed an alternative particulate matter measurement system which is portable and low-cost (less than 200 USD) and also integrated with cloud computing. The system allows real time distant monitoring of PM particles with high spatial resolution (meter range). The developed sensor system is able to provide air quality data in correlation with the existing stations (R-2 = 0.87). The statistical comparison between the developed system and the reference methods revealed that two systems produced statistically equal results in detecting the variations of the particulate matter.
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    A horizontal magnetic tweezer for single molecule micromanipulations
    (IEEE, 345 E 47TH ST, NEW YORK, NY 10017 USA, 2018) Ablay, Gunyaz; Boyuk, Mustafa; Eroglu, Yakup; Icoz, Kutay; 0000-0002-0947-6166; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü
    Magnetic tweezers are able to manipulate cells or biomolecules for various applications and measurements. In this work, a horizontal magnetic tweezer is designed, modeled and controlled for single molecule manipulations. A method is presented for dynamic modeling of horizontal magnetic tweezers. A linear control method is designed to ensure a wide range of operation conditions with zero steady-state error. The horizontal magnetic tweezer is able to generate a wide range of piconewton scale forces on a superparamagnetic microparticle for single molecule separation, and biosensor developments.
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    Article
    Image Processing and Cell Phone Microscopy to Analyze the Immunomagnetic Beads on Micro-Contact Printed Gratings
    (MDPI AG, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2016) Icoz, Kutay; AGÜ, Mühendislik Fakültesi, İnşaat Mühendisliği Bölümü; Icoz, Kutay
    In this paper we report an ultra-low-cost spherical ball lens based cell phone microscopy and image processing algorithms to analyze the amount of immunomagnetic beads on micro-contact printed gratings. The spherical ball lens provides approximately 100x magnification but the recorded images are not clear and are noisy. By using the image-processing algorithms, the noise can be reduced and the images can be enhanced to quantify the amount of immunomagnetic beads on micro-contact printed lines. This method, which is portable and low-cost, can be an alternative read out mechanism for biosensing applications using immunomagnetic beads on micro-contact printed surface receptors. Further, 0.0335 mg/mL was the lowest magnetic bead concentration that could be detected above the inherent noise level of the spherical ball lens.
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    Image-analysis based readout method for biochip: Automated quantification of immunomagnetic beads, micropads and patient leukemia cell
    (PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND, 2020) Uslu, Fatma; Icoz, Kutay; Tasdemir, Kasim; Dogan, Refika S.; Yilmaz, Bulent; 0000-0002-0947-6166; 0000-0003-4542-2728; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü
    For diagnosing and monitoring the progress of cancer, detection and quantification of tumor cells is utmost important. Beside standard bench top instruments, several biochip-based methods have been developed for this purpose. Our biochip design incorporates micron size immunomagnetic beads together with micropad arrays, thus requires automated detection and quantification of not only cells but also the micropads and the immunomagnetic beads. The main purpose of the biochip is to capture target cells having different antigens simultaneously. In this proposed study, a digital image processing-based method to quantify the leukemia cells, immunomagnetic beads and micropads was developed as a readout method for the biochip. Color, size-based object detection and object segmentation methods were implemented to detect structures in the images acquired from the biochip by a bright field optical microscope. It has been shown that manual counting and flow cytometry results are in good agreement with the developed automated counting. Average precision is 85 % and average error rate is 13 % for all images of patient samples, average precision is 99 % and average error rate is 1% for cell culture images. With the optimized micropad size, proposed method can reach up to 95 % precision rate for patient samples with an execution time of 90 s per image.
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    Image-Processing Based Signal Readout Method for MRD Biochip
    (IEEE, 345 E 47TH ST, NEW YORK, NY 10017 USA, 2019) Uslu, Fatma; Icoz, Kutay; Tasdemir, Kasim; 0000-0002-0947-6166; 0000-0003-4542-2728; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü
    The response of the cancer patients to chemotherapy treatment varies from person to person. For some patients cancer cells are resistant to treatment and these cells can relapse again which is known as minimal residual disease. A microfluidic-based biochip capable of monitoring minimal residual disease is under development by our research group. The role of the biochip is to capture the target cells, which were separated by immunomagnetic beads on micro square tiles. Then biochips are imaged using a bright field optical microscope and it is planned to perform image-processing methods to detect the target cells, immunomagnetic beads and micro tiles. In this work the current progress of image processing methods for differentiating the immunomagnetic beads and micro tiles is presented.
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    Immunomagnetic separation of B type acute lymphoblastic leukemia cells from bone marrow with flow cytometry validation and microfluidic chip measurements
    (TAYLOR & FRANCIS INC, 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA, 2020) Icoz, Kutay; Eken, Ahmet; Cinar, Suzan; Murat, Aysegul; Ozcan, Servet; Unal, Ekrem; Deniz, Gunnur; 0000-0002-8330-7010; 0000-0002-0947-6166; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
    In order to detect the blast cells from bone marrow of patients, one strategy is to first isolate the cells using immunomagnetic beads. The aim of this study was to report the experimental results of the immunomagnetic separation efficiency of the blast cells from bone marrow of pediatric leukemia patients. To test the efficiency of immunomagnetic separation, flow cytometry measurements at critical steps were performed. We here reported 94.5% capture efficiency for CD10 nano beads. Patients samples were also analyzed with a microfluidic chip to test the feasibility for further developments.
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    Article
    Improved senescent cell segmentation on bright-field microscopy images exploiting representation level contrastive learning
    (WILEY Online Library, 2024) Çelebi, Fatma; Boyvat, Dudu; Ayaz-Guner, Serife; Tasdemir, Kasim; Icoz, Kutay; 0000-0003-3157-6806; 0000-0002-1052-0961; 0000-0002-0947-6166; 0000-0001-7472-8297; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü; Çelebi, Fatma; Boyvat, Dudu; Ayaz-Guner, Serife; Icoz, Kutay
    Mesenchymal stem cells (MSCs) are stromal cells which have multi-lineage differentiation and self-renewal potentials. Accurate estimation of total number of senescent cells in MSCs is crucial for clinical applications. Traditional manual cell counting using an optical bright-field microscope is timeconsuming and needs an expert operator. In this study, the senescence cells were segmented and counted automatically by deep learning algorithms. However, well-performing deep learning algorithms require large numbers of labeled datasets. The manual labeling is time consuming and needs an expert. This makes deep learning-based automated counting process impractically expensive. To address this challenge, self-supervised learning based approach was implemented. The approach incorporates representation level contrastive learning component into the instance segmentation algorithm for efficient senescent cell segmentation with limited labeled data. Test results showed that the proposed model improves mean average precision and mean average recall of downstream segmentation task by 8.3% and 3.4% compared to original segmentation model.
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    Article
    Improving short-term memory performance of healthy young males using alpha band neurofeedback
    (International Society for Neurofeedback and Research, 2019) Gökşin, Barış; Yılmaz, Bülent; Icoz, Kutay; AGÜ, Mühendislik Fakültesi, Elektrik & Elektronik Mühendisliği Bölümü;
    To examine whether it was possible to improve short-term memory performance of healthy participants by increasing relative alpha band power (7–11.5 Hz) using neurofeedback, we first converted a commercial EEG device (EmotivEpoc) to a neurofeedback tool and collected data from 11 healthy Turkish male graduate students in five neurofeedback sessions. Before and after neurofeedback training, a memorization task using 10 English words and their Turkish meanings was applied to all participants. The results indicated that 6 out of 11 participants were able to enhance their relative alpha band power with respect to other bands in the frequency spectrum during neurofeedback sessions. Although there was no obvious improvement in their short-term memory performance, we may conclude that neurofeedback training was beneficial for the participants to focus their minds consciously. However, it is not easy to mention that neurofeedback training certainly improved or was irrelevant with short-term memory performance. This study is important in the sense that for such a focused group the use of a commercial, customized low-cost EEG device was shown to be feasible for neurofeedback training sessions. © 2019. Gökşin et al.
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    Magnetic micro/nanoparticle flocculation-based signal amplification for biosensing
    (DOVE MEDICAL PRESS LTD, PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND, 07.07.2016) Mzava, Omary; Tas, Zehra; Icoz, Kutay; AGÜ, Mühendislik Fakültesi, Elektrik & Elektronik Mühendisliği Bölümü;
    We report a time and cost efficient signal amplification method for biosensors employing magnetic particles. In this method, magnetic particles in an applied external magnetic field form magnetic dipoles, interact with each other, and accumulate along the magnetic field lines. This magnetic interaction does not need any biomolecular coating for binding and can be controlled with the strength of the applied magnetic field. The accumulation can be used to amplify the corresponding pixel area that is obtained from an image of a single magnetic particle. An application of the method to the Escherichia coli 0157: H7 bacteria samples is demonstrated in order to show the potential of the approach. A minimum of threefold to a maximum of 60-fold amplification is reached from a single bacteria cell under a magnetic field of 20 mT.
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    Article
    Magnetic Separation of Micro Beads and Cells on a Paper-Based Lateral Flow System
    (GAZİ ÜNİVERSİTESİ, 2023) Farooqi, Muhammed Fuad; Icoz, Kutay; 0000-0002-0947-6166; 0000-0003-1883-433X; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü; Farooqi, Muhammed Fuad; Icoz, Kutay
    Paper based lateral flow systems are widely used biosensor platforms to detect biomolecules in a liquid sample. Proteins, bacteria, oligonucleotides, and nanoparticles were investigated in the literature. In this work we designed a magnetic platform including dual magnets and tested the flow of micron size immunomagnetic particles alone and when loaded with cells on two different types of papers. The prewetting conditions of the paper and the applied external magnetic field are the two dominant factors affecting the particle and cell transport in paper. The images recorded with a cell phone, or with a bright field optical microscope were analyzed to measure the flow of particles and cells. The effect of prewetting conditions and magnetic force were measured, and it was shown that in the worst case, minimum 90% of the introduced cells reached to the edge of the paper. The paper based magnetophoretic lateral flow systems can be used for cell assays.
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    Magnetic-particle based signal amplification method integrated with mobile-devices for low cost biosensing
    (ELSEVIER SCIENCE BV, SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS, 2017) Mzava, Omary; Tas, Zehra; Lafci, Vahit Can; Cakar, Mehmet Akif; Ozdur, Ibrahim; Icoz, Kutay; AGÜ, Mühendislik Fakültesi, Mühendislik Bilimleri Bölümü;
    We present a signal amplification method for biosensing applications using magnetic particles. In this method, mobile devices and simple spherical glass beads are used as a low-cost microscope to detect magnetic particles. Magnetic particles have two main functions; 1) conventionally capture, separate and transport target molecules 2) form magnetic dipoles under an applied external magnetic field to attract other magnetized particles. When magnetic particles accumulate and form a cluster, the corresponding pixel area in the image taken by the simple microscope is increased resulting in signal amplification. Current focus of new generation biosensor research is to increase the sensitivity levels of the devices to compete with current lab analysis tools while inherently having other advantages such as being low-cost, portable and simple. Biosensors based on micro/nano magnetic particles use various measurement techniques and amplification methods. In order to fully benefit from the advantages of micro/nano technology based systems, measurement set up must be also portable and have high sensitivity. Mobile devices and applications are taking place in medical fields and have high potential for future. In this work mobile devices are employed as measurement setups for the magnetic particle based sensing and signal amplification. The amplification method is not based on bimolecular binding thus cost efficient. After the images of the magnetic particles are taken, these images are sent to cloud computing for analysis by the mobile device. Matlab codes run on cloud servers for processing the images. Finally results are received and displayed on the mobile device. The mobile device based imaging system is able to detect 7 mu m size particles within a 1500 mu m x1500 mu m area and magnetic bead accumulation resulted in at least 5-fold signal amplification. The applied magnetic field is approximately 15 mT and the cost of the system excluding mobile device is under 20 cents. The method is promising for immunomagnetic bead assisted biosensors. (c) 2016 The Authors. Published by Elsevier Ltd.
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    Micro- and nanodevices integrated with biomolecular probes
    (PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND, 2015) Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A.; AGÜ, Mühendislik Fakültesi, Elektrik & Elektronik Mühendisliği Bölümü;
    Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. (C) 2015 Elsevier Inc. All rights reserved.
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    Microfluidic Chip based direct triple antibody immunoassay for monitoring patient comparative response to leukemia treatment
    (SPRINGER, VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS, 2020) Icoz, Kutay; Akar, Unal; Unal, Ekrem; 0000-0002-0947-6166; 0000-0002-0000-8999; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü
    We report a time and cost-efficient microfluidic chip for screening the leukemia cells having three specific antigens. In this method, the target blast cells are double sorted with immunomagnetic beads and captured by the 3rd antibody immobilized on the gold surface in a microfluidic chip. The captured blast cells in the chip were imaged using a bright-field optical microscope and images were analyzed to quantify the cells. First sorting was performed with nano size immunomagnetic beads and followed by 2nd sorting where micron size immunomagnetic beads were used. The low-cost microfluidic platform is made of PMMA and glass including micro size gold pads. The developed microfluidic platform was optimized with cultured B type lymphoblast cells and tested with the samples of leukemia patients. The 8 bone marrow samples of 4 leukemia patients on the initial diagnosis and on the 15th day after the start of the chemotherapy treatment were tested both with the developed microfluidic platform and the flow cytometry. A 99% statistical agreement between the two methods shows that the microfluidic chip is able to monitor the decrease in the number of blast cells due to the chemotherapy. The experiments with the patient samples demonstrate that the developed system can perform relative measurements and have a potential to monitor the patient response to the applied therapy and to enable personalized dose adjustment.
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    Review
    Molecular Separation by Using Active and Passive Microfluidic chip Designs: A Comprehensive Review
    (WILEY Advanced, 2024) Ebrahimi, Aliakbar; Icoz, Kutay; Didarian, Reza; Shih, Chih-Hsin; Tarim, E. Alperay; Nasseri, Behzad; Akpek, Ali; Cecen, Berivan; Bal-Ozturk, Ayca; Gulec, Kadri; Li, Yi-Chen Ethan; Shih, Steven; Tarim, Burcu Sirma; Tekin, H. Cumhur; Alarcin, Emine; Tayybi-Azar, Mehdi; Ghorbanpoor, Hamed; Ozel, Ceren; Sariboyaci, Ayla Eker; Guzel, Fatma Dogan; Bassous, Nicole; Shin, Su Ryon; Avci, Huseyin; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü; Icoz, Kutay
    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.
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