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Breath as the mirror of our body is the answer really blowing in the wind? Recent technologies in exhaled breath analysis systems as non-invasive sensing platforms
(Elsevier Sci Ltd, 2021) Beduk, Tutku; Durmus, Ceren; Hanoglu, Simge Balaban; Beduk, Duygu; Salama, Khaled Nabil; Goksel, Tuncay; Turhan, Kutsal
Health care monitoring is an enormous field of research that has great potential to solve many problems in human life. In recent years, non-invasive health monitoring has become a prerequisite for early diagnosis of various diseases such as lung cancer, oxidative stress, diabetes, to enable the prompt treatment and screening of crucial chemicals. Although analyzing of exhaled breath has been correlated with advanced analytical techniques such as gas chromatography and infrared spectroscopy, breath analyzing biosensing systems offer a cost-effective, sensitive platform for a straightforward analysis. However, current non-invasive sensing strategies have been lacking in practicality in terms of the design and usage, on-site ability and accessibility. This review will critically discuss current commercialized breath analyzers, the recent achievements for the use of the detection towards chemical and biological substances from exhaled breath as non-invasive sensing systems including challenges/drawbacks by addressing the practical applications and concerns in the field. The different fabrication strategies, methodology of detection techniques involved in the development of the breath analyzing systems will be overviewed and discussed along with the future opportunities for possible point of care applications with smartphone integration in this review. The scientific and technological challenges in the field are discussed in the conclusion. (C) 2021 Elsevier B.V. All rights reserved.
Catechol-Attached Polypeptide with Functional Groups as Electrochemical Sensing Platform for Synthetic Cannabinoids
(Amer Chemical Soc, 2020) Durmus, Ceren; Aydindogan, Eda; Gumus, Zinar Pinar; Endo, Takeshi; Yamada, Shuhei; Coskunol, Hakan; Yagci, Yusuf
Herein, we first constructed a functional surface using a catechol-attached polypeptide (CtP) for the detection of JWH-018 (N-4-hydroxypentyl metabolite). K2 antibody was then incorporated to the polymer via covalent cross-linker. Step-by-step modifications on the glassy carbon electrode surface were characterized by electrochemical measurements such as differential pulse voltammetry, cyclic voltammetry, impedance spectroscopy, and X-ray photoelectron spectroscopy. Linearity and the limit of detection for JWH-018 (N-4-hydroxypentyl metabolite) were determined as 10-500 ng/mL with an equation of y = 0.0018x + 0.136 (R-2 = 0.993) and 5.892 ng/mL, respectively. the selectivity of the biosensor was evaluated with different interfering molecules (methamphetamine, codeine, and cocaine). Finally, the biosensor was successfully used in the determination of JWH-018 (N-4-hydroxypentyl metabolite) in spiked synthetic urine samples, and a high-performance liquid chromatography (HPLC) system was used as a reference method to confirm the sample application. the results show that this biosensor platform can be applied to detect other JWH series of synthetic cannabinoids with high sensitivity and accuracy.
Dye-Loaded Polymersome-Based Lateral Flow Assay: Rational Design of a COVID-19 Testing Platform by Repurposing SARS-CoV-2 Antibody Cocktail and Antigens Obtained from Positive Human Samples
(Amer Chemical Soc, 2021) Ghorbanizamani, Faezeh; Tok, Kerem; Moulahoum, Hichem; Harmanci, Duygu; Hanoglu, Simge Balaban; Durmus, Ceren; Zihnioglu, Figen
The global pandemic of COVID-19 continues to be an important threat, especially with the fast transmission rate observed after the discovery of novel mutations. In this perspective, prompt diagnosis requires massive economical and human resources to mitigate the disease. The current study proposes a rational design of a colorimetric lateral flow immunoassay (LFA) based on the repurposing of human samples to produce COVID-19-specific antigens and antibodies in combination with a novel dye-loaded polymersome for naked-eye detection. A group of 121 human samples (61 serums and 60 nasal swabs) were obtained and analyzed by RT-PCR and ELISA. Pooled samples were used to purify antibodies using affinity chromatography, while antigens were purified via magnetic nanoparticles-based affinity. The purified proteins were confirmed for their specificity to COVID-19 via commercial LFA, ELISA, and electrochemical tests in addition to sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Polymersomes were prepared using methoxy polyethylene glycol-b-polycaprolactone (mPEG-b-PCL) diblock copolymers and loaded with a Coomassie Blue dye. The polymersomes were then functionalized with the purified antibodies and applied for the preparation of two types of LFA (antigen test and antibody test). Overall, the proposed diagnostic tests demonstrated 93 and 92.2% sensitivity for antigen and antibody tests, respectively. The repeatability (92-94%) and reproducibility (96-98%) of the tests highlight the potential of the proposed LFA. The LFA test was also analyzed for stability, and after 4 weeks, 91-97% correct diagnosis was observed. The current LFA platform is a valuable assay that has great economical and analytical potential for widespread applications.
An Electrochemical Biosensor Platform for Testing of Dehydroepiandrosterone 3-Sulfate (DHEA-S) as a Model for Doping Materials
(Wiley-V C H Verlag Gmbh, 2019) Balaban, Simge; Durmus, Ceren; Aydindogan, Eda; Gumus, Zinar Pinar; Timur, Suna
Endogenous steroids such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) have commonly used as doping materials by athletes and to date novel techniques are needed for detection of these molecules. In this study, antibody-based electrochemical biosensor has developed for testing level of the DHEA-S. For this aim, gold surfaces were initially modified with cysteamine (Cys) and then, DHEA-S antibody was immobilized on the surface via glutaraldehyde (GA) as a crosslinking agent. The stepwise modification of electrode surface was monitored by using various electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Linear range was determined as 2.5-100 ng/mL DHEA-S using differential pulse voltammetry (DPV) technique, as well. Moreover, repeatability (+/- S.D.), coefficient of variation (%) and limit of detection (LOD) values were calculated as 0.033, 1.030 and 3.971, respectively. Also, DHEA-S in synthetic serum and urine samples were successfully determined with standard addition method and confirmation analysis were performed with liquid chromatography quadrupole-time of flight mass spectrometry (LC-QTOF/MS) system. The selectivity was studied with the addition of some interfering molecules (testosterone, bovine serum albumin (BSA), cholesterol, uric acid, lactic acid, codein (COD), ascorbic acid, DHEA). Consequently, this work is proposed as practical, innovative and cost-effective technique that can be easily adapted for the miniaturized form for the analysis of other doping substances as well as DHEA-S for the future works.
An Electrochemical Biosensor Platform for Testing of Dehydroepiandrosterone 3-Sulfate (DHEA-S) as a Model for Doping Materials
(Wiley-V C H Verlag Gmbh, 2020) Balaban, Simge; Durmus, Ceren; Aydindogan, Eda; Gumus, Zinar Pinar; Timur, Suna
Endogenous steroids such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) have commonly used as doping materials by athletes and to date novel techniques are needed for detection of these molecules. In this study, antibody-based electrochemical biosensor has developed for testing level of the DHEA-S. For this aim, gold surfaces were initially modified with cysteamine (Cys) and then, DHEA-S antibody was immobilized on the surface via glutaraldehyde (GA) as a crosslinking agent. The stepwise modification of electrode surface was monitored by using various electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Linear range was determined as 2.5-100 ng/mL DHEA-S using differential pulse voltammetry (DPV) technique, as well. Moreover, repeatability (+/- S.D.), coefficient of variation (%) and limit of detection (LOD) values were calculated as 0.033, 1.030 and 3.971, respectively. Also, DHEA-S in synthetic serum and urine samples were successfully determined with standard addition method and confirmation analysis were performed with liquid chromatography quadrupole-time of flight mass spectrometry (LC-QTOF/MS) system. The selectivity was studied with the addition of some interfering molecules (testosterone, bovine serum albumin (BSA), cholesterol, uric acid, lactic acid, codein (COD), ascorbic acid, DHEA). Consequently, this work is proposed as practical, innovative and cost-effective technique that can be easily adapted for the miniaturized form for the analysis of other doping substances as well as DHEA-S for the future works.
Electrochemical sensors and biosensors using laser-derived graphene: A comprehensive review
(Elsevier Advanced Technology, 2020) Lahcen, Abdellatif Ait; Rauf, Sakandar; Beduk, Tutku; Durmus, Ceren; Aljedaibi, Abdulrahman; Timur, Suna; Salama, Khaled N.
Laser-derived graphene (LDG) technology is gaining attention as a promising material for the development of novel electrochemical sensors and biosensors. Compared to established methods for graphene synthesis, LDG provides many advantages such as cost-effectiveness, fast electron mobility, mask-free, green synthesis, good electrical conductivity, porosity, mechanical stability, and large surface area. This review discusses, in a critical way, recent advancements in this field. First, we focused on the fabrication and doping of LDG platforms using different strategies. Next, the techniques for the modification of LDG sensors using nanomaterials, conducting polymers, biological and artificial receptors are presented. We then discussed the advances achieved for various LDG sensing and biosensing schemes and their applications in the fields of environmental monitoring, food safety, and clinical diagnosis. Finally, the drawbacks and limitations of LDG based electrochemical biosensors are addressed, and future trends are also highlighted.
in vitro Selection of Aptamer for Imidacloprid Recognition as Model Analyte and Construction of a Water Analysis Platform
(Wiley-V C H Verlag Gmbh, 2020) Bor, Gulsah; Man, Ezgi; Ugurlu, Ozge; Ceylan, Ayse Elcin; Balaban, Simge; Durmus, Ceren; Timur, Suna
Pesticide use in agriculture is one of the threats to water safety. Therefore, detection of pesticide residues is crucial for human health. Compared to conventional chromatographic methods, aptasensors are promising tools for fast, cheap and sensitive detection of environmental contaminants. To the best of our knowledge, such an aptasensor has not been reported for imidacloprid (Imi) which is one of the most widely used pesticides. in order to meet this demand, we initially selected two novel aptamers designated as 'Apta-1' and 'Apta-2' by graphene oxide-SELEX (GO-SELEX) method. Then, these aptamers were used to fabricate the gold electrode-based aptasensor platforms and characterized by using electrochemical methods such as cyclic voltammetry, and electrochemical impedance spectroscopy as well as X-Ray photoelectron spectroscopy. It was found that the limit of detection value of Apta-1 based sensor for the Imi was found better than Apta-2 based system, although linear ranges were similar. Based on that finding, Apta-1 based system was further tested against possible interference molecules. the proposed platform was successfully used for detection of very low concentrations of Imi in the range of ng/mL. Thus, it eliminates the need for sample pre-treatment and enables a practical analysis in real wastewater samples.
Indiscriminate SARS-CoV-2 multivariant detection using magnetic nanoparticle-based electrochemical immunosensing
(Elsevier, 2022) Durmus, Ceren; Harmanci, Duygu; Moulahoum, Hichem; Tok, Kerem; Ghorbanizamani, Faezeh; Sanli, Serdar; Zihnioglu, Figen
The increasing mutation frequency of the SARS-CoV-2 virus and the emergence of successive variants have made correct diagnosis hard to perform. Developing efficient and accurate methods to diagnose infected patients is crucial to effectively mitigate the pandemic. Here, we developed an electrochemical immunosensor based on SARS-CoV-2 antibody cocktail-conjugated magnetic nanoparticles for the sensitive and accurate detection of the SARS-CoV-2 virus and its variants in nasopharyngeal swabs. The application of the antibody cocktail was compared with commercially available anti-SARS-CoV-2 S1 (anti-S1) and anti-S2 monoclonal antibodies. After optimization and calibration, the limit of detection (LOD) determination demonstrated a LOD = 0.53-0.75 ng/ mL for the antibody cocktail-based sensor compared with 0.93 ng/mL and 0.99 ng/mL for the platforms using anti-S1 and anti-S2, respectively. The platforms were tested with human nasopharyngeal swab samples pre diagnosed with RT-PCR (10 negatives and 40 positive samples). The positive samples include the original, alpha, beta, and delta variants (n = 10, for each). The polyclonal antibody cocktail performed better than commercial anti-S1 and anti-S2 antibodies for all samples reaching 100% overall sensitivity, specificity, and accuracy. It also showed a wide range of variants detection compared to monoclonal antibody-based platforms. The present work proposes a versatile electrochemical biosensor for the indiscriminate detection of the different variants of SARS-CoV-2 using a polyclonal antibody cocktail. Such diagnostic tools allowing the detection of variants can be of great efficiency and economic value in the fight against the ever-changing SARS-CoV-2 virus.
Laser-scribed Graphene Electrodes as an Electrochemical Immunosensing Platform for Cancer Biomarker 'eIF3d'
(Wiley-V C H Verlag Gmbh, 2021) Balaban, Simge; Beduk, Tutku; Durmus, Ceren; Aydindogan, Eda; Salama, Khaled Nabil; Timur, Suna
eIF3d is a protein biomarker which has a potential for the diagnosis of various cancers. Herein, a bio-platform was constructed for eIF3d sensing by using LSG and surface functionalization with anti eIF3d antibody via EDC/NHS chemistry. Following the surface modifications, XPS and several electrochemical methods were used. Difference in the signals were related to biomarker amounts between 75-500 ng/mL. LOD was calculated as 50.4 ng/mL. Selectivity of biosensor was tested by using of various interference molecules. EIF3d was also successfully detected in synthetic biological samples. Thus, to the best of our knowledge, this study is one of the rare studies on use of LSGs in immunosensor studies.
Metal-Organic Frameworks Meet Molecularly Imprinted Polymers: Insights and Prospects for Sensor Applications
(Amer Chemical Soc, 2022) Lahcen, Abdellatif Ait; Surya, Sandeep G.; Beduk, Tutku; Vijjapu, Mani Teja; Lamaoui, Abderrahman; Durmus, Ceren; Timur, Suna
The use of porous materials as the core for synthesizing molecularly imprinted polymers (MIPs) adds significant value to the resulting sensing system. This review covers in detail the current progress and achievements regarding the synergistic combination of MIPs and porous materials, namely metal/covalent-organic frameworks (MOFs/COFs), including the application of such frameworks in the development of upgraded sensor platforms. The different processes involved in the synthesis of MOF/COF-MIPs are outlined, along with their intrinsic properties. Special attention is paid to debriefing the impact of the morphological changes that occur through the synergistic combination compared to those that occur due to the individual entities. Thereafter, the strategies used for building the sensors, as well as the transduction modes, are overviewed and discussed. This is followed by a full description of research advances for various types of MOF/COF-MIP-based (bio)sensors and their applications in the fields of environmental monitoring, food safety, and pharmaceutical analysis. Finally, the challenges/drawbacks, as well as the prospects of this research field, are discussed in detail.
Metal-Organic Frameworks Meet Molecularly Imprinted Polymers: Insights and Prospects for Sensor Applications
(Amer Chemical Soc, 2022) Lahcen, Abdellatif Ait; Surya, Sandeep G.; Bedük, Tutku; Vijjapu, Mani Teja; Lamaoui, Abderrahman; Durmus, Ceren; Timur, Suna
The use of porous materials as the core for synthesizing molecularly imprinted polymers (MIPs) adds significant value to the resulting sensing system. This review covers in detail the current progress and achievements regarding the synergistic combination of MIPs and porous materials, namely metal/covalent-organic frameworks (MOFs/COFs), including the application of such frameworks in the development of upgraded sensor platforms. The different processes involved in the synthesis of MOF/COF-MIPs are outlined, along with their intrinsic properties. Special attention is paid to debriefing the impact of the morphological changes that occur through the synergistic combination compared to those that occur due to the individual entities. Thereafter, the strategies used for building the sensors, as well as the transduction modes, are overviewed and discussed. This is followed by a full description of research advances for various types of MOF/COF-MIP-based (bio)sensors and their applications in the fields of environmental monitoring, food safety, and pharmaceutical analysis. Finally, the challenges/drawbacks, as well as the prospects of this research field, are discussed in detail.
Metal-Organic Frameworks Meet Molecularly Imprinted Polymers: Insights and Prospects for Sensor Applications [Review]
(Amer Chemical Soc, 2022) Lahcen, Abdellatif Ait; Surya, Sandeep G.; Beduk, Tutku; Vijjapu, Mani Teja; Lamaoui, Abderrahman; Durmus, Ceren; Timur, Suna
The use of porous materials as the core for synthesizing molecularly imprinted polymers (MIPs) adds significant value to the resulting sensing system. This review covers in detail the current progress and achievements regarding the synergistic combination of MIPs and porous materials, namely metal/covalent-organic frameworks (MOFs/COFs), including the application of such frameworks in the development of upgraded sensor platforms. The different processes involved in the synthesis of MOF/COF-MIPs are outlined, along with their intrinsic properties. Special attention is paid to debriefing the impact of the morphological changes that occur through the synergistic combination compared to those that occur due to the individual entities. Thereafter, the strategies used for building the sensors, as well as the transduction modes, are overviewed and discussed. This is followed by a full description of research advances for various types of MOF/COF-MIP-based (bio)sensors and their applications in the fields of environmental monitoring, food safety, and pharmaceutical analysis. Finally, the challenges/drawbacks, as well as the prospects of this research field, are discussed in detail.
Multiplexed sensing techniques for cardiovascular disease biomarkers- A review
(Elsevier Advanced Technology, 2022) Mani, Veerappan; Durmus, Ceren; Khushaim, Walaa; Ferreira, Daisy Camargo; Timur, Suna; Arduini, Fabiana; Salama, Khaled Nabil
Cardiovascular diseases (CVDs) are the number one cause of death worldwide, taking 17.9 million lives each year. The rapid, sensitive, and accurate determination of cardiac biomarkers is vital for the timely diagnosis of CVDs. For accurate diagnosis, dependence on a single biomarker is unreliable because each one has also been linked to other diseases. To overcome this problem, the multiplexed determination of two or more markers has emerged as a promising alternative to single-marker analysis. Over the last 5 years, research interest in the development of biosensors for targeting multiple cardiac markers has increased. In this study, we critically reviewed the various multiplexed biosensing approaches reported during the last 5 years, categorizing them by signal readouts. Prospective detection configurations, capture probes, electrode design strategies, electrode types, nanomaterials, reporter tags, and assay types were reviewed, tabulated, and critically discussed. Then, their advantages and limitations were highlighted. For each category, we provided our perspective as well as the overall critical discussion. Lastly, we summarized potential commercial multiplexed cardiac biosensors and commented on the challenges and future prospects for such sensors.
Sensor Platform with a Custom-Tailored Aptamer for Diagnosis of Synthetic Cannabinoids
(Wiley-V C H Verlag Gmbh, 2020) Balaban, Simge; Man, Ezgi; Durmus, Ceren; Bor, Gulsah; Ceylan, Ayse Elcin; Gumus, Z. Pinar; Timur, Suna
Synthetic cannabinoids (SCs) are the large group of abused drugs and detection of them is still a challenge. Hence, new methods for analysis of SCs are being investigated. We aimed to develop a novel system for selective analysis of SCs. First, various custom-tailored aptamers against the target SCs were selected through GO-SELEX process. Toggling between different SC analytes during successive rounds of selection was performed to generate cross-reactive aptamers. Then, the amino-capped aptamers were synthesized and easily attached to the cysteamine-covered gold electrodes. Analytical parameters and selectivity of the aptasensors were compared by using electrochemical techniques. After comparison of the analytical features and selectivity towards target analytes, one of the aptamers designated as Apta-1 was chosen for further measurements. the aptasensor was tested by using differential pulse voltammetry technique against JWH-018 (5-pentanoic acid), selected as a model for SCs. the linearity and limit of detection were determined as 0.01-1.0 ng/mL and 0.036 ng/mL. Finally, sample application in synthetic urine samples was successfully performed with standard addition method, as confirmed by LC-QTOF/MS. JWH-018 (4-hydroxypentyl), JWH-073 (3-hydroxybutyl), JWH-250 (5-hidroxypentyl) and HU-210 were used to test the selectivity of the aptasensor and the system was shown to recognize all these SCs. Also other illegal drugs did not significantly interfere with the signal responses.
Simple workflow to repurpose SARS-CoV-2 swab/serum samples for the isolation of cost-effective antibody/antigens for proteotyping applications and diagnosis
(Springer Heidelberg, 2021) Tok, Kerem; Moulahoum, Hichem; Ghorbanizamani, Faezeh; Harmanci, Duygu; Hanoglu, Simge Balaban; Durmus, Ceren; Evran, Serap
Supply shortage for the development and production of preventive, therapeutic, and diagnosis tools during the COVID-19 pandemic is an important issue affecting the wealthy and poor nations alike. Antibodies and antigens are especially needed for the production of immunological-based testing tools such as point-of-care tests. Here, we propose a simple and quick magnetic nanoparticle (MNP)-based separation/isolation approach for the repurposing of infected human samples to produce specific antibodies and antigen cocktails. Initially, an antibody cocktail was purified from serums via precipitation and immunoaffinity chromatography. Purified antibodies were conjugated onto MNPs and used as an affinity matrix to separate antigens. The characterization process was performed by ELISA, SDS-PAGE, electrochemistry, isothermal titration calorimetry, and LC-Q-TOF-MS/MS analyses. The MNP-separated peptides can be used for mass spectrometry-based as well as paper-based lateral flow assay diagnostic. The exploitation of the current workflow for the development of efficient diagnostic tools, specific treatments, and fundamental research can significantly impact the present or eventual pandemic. This workflow can be considered as a two birds, one stone-like strategy.

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