Browsing by Author "Icoz, Kutay"

Now showing 1 - 20 of 30

Citation - WoS: 12
Citation - Scopus: 14
Detection of Proteins Using Nano Magnetic Particle Accumulation-Based Signal Amplification
(MDPI, 2016) Icoz, Kutay; Mzava, Omary
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.
Citation - WoS: 16
Citation - Scopus: 18
Microfluidic Chip Based Direct Triple Antibody Immunoassay for Monitoring Patient Comparative Response to Leukemia Treatment
(Springer, 2020) Icoz, Kutay; Akar, Unal; Unal, Ekrem
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.
Citation - WoS: 5
Citation - Scopus: 9
Image Processing and Cell Phone Microscopy to Analyze the Immunomagnetic Beads on Micro-Contact Printed Gratings
(MDPI Ag, 2016) 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.
Ball Lens Based Mobile Microscope
(Gazi Univ, 2016) 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.
Citation - WoS: 2
Citation - Scopus: 3
Magnetic Separation of Micro Beads and Cells on a Paper-Based Lateral Flow System
(Gazi Univ, 2023) 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.
Citation - WoS: 6
Citation - Scopus: 8
Immunomagnetic Separation of B Type Acute Lymphoblastic Leukemia Cells from Bone Marrow With Flow Cytometry Validation and Microfluidic Chip Measurements
(Taylor & Francis inc, 2021) Icoz, Kutay; Eken, Ahmet; Cinar, Suzan; Murat, Aysegul; Ozcan, Servet; Unal, Ekrem; Deniz, Gunnur
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.
Citation - WoS: 22
Citation - Scopus: 29
Automated Quantification of Immunomagnetic Beads and Leukemia Cells from Optical Microscope Images
(Elsevier Sci Ltd, 2019) Uslu, Fatma; Icoz, Kutay; Tasdemir, Kasim; Yilmaz, Bulent
Quantification of tumor cells is crucial for early detection and monitoring the progress of cancer. Several methods have been developed for detecting tumor cells. However, automated quantification of cells in the presence of immunomagnetic beads has not been studied. In this study, we developed computer vision based algorithms to quantify the leukemia cells captured and separated by micron size immunomagnetic beads. Color, size based object identification and machine learning based methods were implemented to quantify targets in the images recorded by a bright field microscope. Images acquired by a 40x or a 20x objective were analyzed, the immunomagnetic beads were detected with an error rate of 0.0171 and 0.0384 respectively. Our results reveal that the proposed method attains 91.6% precision for the 40x objective and 79.7% for the 20x objective. This algorithm has the potential to be the signal readout mechanism of a biochip for cell detection. (C) 2019 Elsevier Ltd. All rights reserved.
Magnetic-Particle Based Signal Amplification Method Integrated With Mobile-Devices for Low Cost Biosensing
(Elsevier Science Bv, 2017) Mzava, Omary; Tas, Zehra; Lafci, Vahit Can; Cakar, Mehmet Akif; Ozdur, Ibrahim; Icoz, Kutay
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.
Citation - WoS: 3
Citation - Scopus: 5
Feedback Controller Designs for an Electromagnetic Micromanipulator
(Sage Publications Ltd, 2020) Boyuk, Mustafa; Eroglu, Yakup; Ablay, Gunyaz; Icoz, Kutay
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.
Citation - WoS: 7
Citation - Scopus: 8
Using Students' Performance to Improve Ontologies for Intelligent E-Learning System
(Edam, 2015) Icoz, Kutay; Sanalan, Vehbi A.; Cakar, Mehmet Akif; Ozdemir, Esra Benli; Kaya, Sukru
Ontologies have often been recommended for E-learning systems, but few efforts have successfully incorporated student data to represent knowledge conceptualizations. Defining key concepts and their relations between each other establishes the backbone of our E-learning system. The system guides an individual student through his/her course by evaluating their progress and suggesting instructional material to review based upon their answers. Three main tasks are performed within this framework: building ontologies for the course, measuring a student's understanding level for the concepts, and making personal suggestions to create an individualized learning environment. This paper presents: the integration of ontologies, assisted with student data, together with an intelligent Recommendation Module for the development of an E-learning system; the comparison and correction adaption of ontology from students' mind maps; and the assessment of students' actual weaknesses in comparison to what Recommendation Module suggests. The sample of 127 students, five classrooms, was conveniently selected among seventh grade students of a demographically average school in a major city in Turkey. The students' achievement was assessed and the scores for different questions were investigated for associations with concepts made in the students' minds. The results provided significant correlations among scores, and a fit model for the concepts represented by questions. The student suggested model slightly differed from the ontology map from the experts. Based on the data-supported model, the Recommendation Module more accurately determined the students' learning deficiencies and suggested concepts to be reviewed.
Citation - WoS: 2
Citation - Scopus: 4
High Spatial Resolution IoT Based Air PM Measurement System
(Springer, 2021) 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.
Citation - WoS: 5
Citation - Scopus: 6
Design, Modeling, and Control of a Horizontal Magnetic Micromanipulator
(Sage Publications Ltd, 2019) Ablay, Gunyaz; Boyuk, Mustafa; Icoz, Kutay
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.
Citation - WoS: 15
Citation - Scopus: 16
Magnetic Micro/Nanoparticle Flocculation-Based Signal Amplification for Biosensing
(Dove Medical Press Ltd, 2016) Mzava, Omary; Tas, Zehra; Icoz, Kutay
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.
Citation - WoS: 16
Citation - Scopus: 20
Parameter Investigation of Topological Data Analysis for EEG Signals
(Elsevier Sci Ltd, 2021) Altindis, Fatih; Yilmaz, Bulent; Borisenok, Sergey; Icoz, Kutay
Topological data analysis (TDA) methods have become appealing in EEG signal processing, because they may help the scientists explore new features of complex and large amount of data by simplifying the process from a geometrical perspective. Time delay embedding is a common approach to embed EEG signals into the state space. Parameters of this embedding method are variable and the structure of the state space can be entirely different depending on their selection. Additionally, extracted persistent homologies of the state spaces depend on filtration level and the number of points used. In this study, we showed how to adapt false nearest neighbor (FNN) test to find out the suitable/optimal time embedding parameters (i.e., time delay and embedding dimension) for EEG signals, and compared their effects on different types of artefacts and motor intention waves that are commonly used in brain-computer interfaces. We extracted and compared persistent homologies of state spaces that were reconstructed with four different sets of parameters. Later, the effect of filtration level on extracted persistent homologies was compared, and statistical significance levels were computed between leftand right-hand movement imaginations. Finally, computational cost of the discussed methods was found, and the adaptability of this method to a real-time application was evaluated. We demonstrated that the discussed parameters of the TDA approach were highly crucial to extract true topological features of the EEG signals, and the adapted testing approaches depicted the applicability of this approach on real-time analysis of EEG signals.
Citation - WoS: 9
Citation - Scopus: 10
Numerical Analysis and Experimental Verification of Optical Scattering From Microplastics
(Royal Soc, 2023) Genc, Sinan; Icoz, Kutay; Erdem, Talha
Accurate and fast characterization of the micron-sized plastic particles in aqueous media requires an in-depth understanding of light interaction with these particles. Due to the complexity of Mie scattering theory, the features of the scattered light have rarely been related to the physical properties of these tiny objects. To address this problem, we reveal the relation of the wavelength-dependent optical scattering patterns with the size and refractive index of the particles by numerically studying the angular scattering features. We subsequently present a low-cost setup to measure the optical scattering of the particles. Theoretical investigation shows that the angular distribution of the scattered light by microplastics carries distinct signatures of the particle size and the refractive index. The results can be used to develop a portable, low-cost setup to detect microplastics in water.
Citation - WoS: 28
Citation - Scopus: 34
Micro- and Nanodevices Integrated With Biomolecular Probes
(Pergamon-Elsevier Science Ltd, 2015) Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A.
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.
Citation - WoS: 2
Citation - Scopus: 5
Simple Staining of Cells on a Chip
(MDPI, 2022) Kosker, Fatma Betul; Aydin, Omer; Icoz, Kutay
Simple staining of cells is a widely used method in basic medical diagnostics, education, and research laboratories. The stains are low-cost, but the extensive consumption results in excessive toxic waste generation. Thus, to decrease the amount of toxic waste resulting from the cell staining procedure is a need. In this study, we developed a magnetically driven and compartmentalized passive microfluidic chip to perform simple staining of human eukaryotic cells, K562 cells, and lymphocyte cells derived from patients. We demonstrated simple staining on cells with trypan blue, methylene blue, crystal violet, and safranin for high, medium, and low cell densities. The stained cells were imaged using a bright field optical microscope and a cell phone to count cells on the focal plane. The staining improved the color signal of the cell by 25-135-pixel intensity changes for the microscopic images. The validity of the protocol was determined using Jurkat and MDA-MB-231 cell lines as negative controls. In order to demonstrate the practicality of the system, lymphocyte cells derived from human blood samples were stained with trypan blue. The color intensity changes in the first and last compartments were analyzed to evaluate the performance of the chip. The developed method is ultra-low cost, significantly reduces the waste generated, and can be integrated with mobile imaging devices in terms of portability. By combining microfabrication technology with cell staining, this study reported a novel contribution to the field of microfluidic biosensors. In the future, we expect to demonstrate the detection of pathogens using this method.
Citation - WoS: 16
Citation - Scopus: 19
On-Demand Weighing of Single Dry Biological Particles Over a 5-Order Dynamic Range
(Royal Soc Chemistry, 2014) Chan, Bin-Da; Icoz, Kutay; Huang, Wanfeng; Chang, Chun-Li; Savran, Cagri A.
We report a simple and highly versatile system to select and weigh individual dry biological particles. The system is composed of a microtweezer to pick and place individual particles and a cantilever-based resonator to weigh them. The system can weigh entities that vary from a red blood cell (similar to 10(-11) g) to the eye-brain complex of an insect (similar to 10(-6) g), covering a 5-order-of-magnitude mass range. Due to its versatility and ease of use, this weighing method is highly compatible with established laboratory practices. The system can provide complementary mass information for a wide variety of individual particles imaged using scanning electron microscopy and determine comparative weights of individual biological entities that are attached to microparticles as well as weigh fractions of individual biological entities that have been subjected to focused ion beam milling.
Citation - WoS: 13
Citation - Scopus: 14
Image-Analysis Based Readout Method for Biochip: Automated Quantification of Immunomagnetic Beads, Micropads and Patient Leukemia Cell
(Pergamon-Elsevier Science Ltd, 2020) Uslu, Fatma; Icoz, Kutay; Tasdemir, Kasim; Dogan, Refika S.; Yilmaz, Bulent
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.
Citation - WoS: 30
Citation - Scopus: 33
Molecular Separation by Using Active and Passive Microfluidic Chip Designs: A Comprehensive Review
(Wiley, 2024) Ebrahimi, Aliakbar; Icoz, Kutay; Didarian, Reza; Shih, Chih-Hsin; Tarim, E. Alperay; Nasseri, Behzad; Avci, Huseyin
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. This review is about the microfludic-based methods that have been used in the past two decades for the separation of different biomolecules like protein, DNA, and RNA. In this regard, passive, active, and hybrid microfludic methods that are used for biomolecules separation are disscused and reviewed in this paper.image