Development of nanoparticle-modified sensor platform for cancer marker detection

The detection and quantification of cancer biomarkers in human blood is crucial to diagnose patients in the early stage of a disease. The recent advances in biosensor technology can improve detection by reducing the application time and cost without an invasive approach. The development of such detection system is a major thrust of the rapidly growing biotechnology industry. It involves a multidisciplinary research effort including chemical engineering, microelectronics and biology. This study focused on the development of nanomaterial-modified sensing platform to enhance the sensitivity for cancer marker detection. An electrochemical-based capacitive biosensor was aimed to develop using two alternative nanomaterial modification including gold nanoparticles (Au-NPs) and magnetic beads (MBs) in cancer detection for the first time. Surface Plasmon resonanse (SPR) and quartz crystal microbalance (QCM)-based sensors were initially employed to verify the bioassays and the surface chemistries. The successful achievement of these research works was transferred into an electrochemical based-capacitive biosensor to increase the sensitivity and reliability of the assays for the quantification of the biological markers. The optimized sensor methods were conducted in the capacitive sensor using standard methodologies and the detection limit was increased 6 fold without a signal amplification tool. However, the quantification of some biomarkers is difficult since they have trace threshold level in human blood and/or small size. Moreover, real patient samples include various biological molecules beside the target analyte and this makes the detection difficult due to the non-specific responses and requires the signal amplification. Due to these reasons, a novel nanoparticle modified capacitive sensor was developed and used for synchronous multiple marker detection for the first time. The developed sensor increased the sensitivity up to 600 fold (5 pg.mL-1) when compared with standard sensor assays. The results have provided alternative and effective quantification approaches to the current tools; and also a promising future for precise detection of the cancer types using multiple marker assays. The developed and improved methodologies/sensors in this thesis can also be applied for the other diseases that have biomarkers in human body

Characteristics of food allergy in children: National multicenter study

Conference: Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) Location: Lisbon, PORTUGAL Date: JUN 01-05, 2019Background : Food allergies impose a significant burden on the life of the child and the family. In this study, to determine the demographic characteristics of food allergies, we investigated the characteristics of patients with food allergies in different regions of Pediatric Allergy- Immunology departments in Turkey. Method : Turkey ' s National Study of Allergy and Clinical Immunology Society has conducted a Study Group on Food Allergies. 25 centers participated in this multicenter, cross- sectional and descriptive study.European Academy of Allergy and Clinical Immunolog

DNA-based biosensor platforms for the detection of TP53 mutation

A DNA-based assay for the detection of one-point mutation in TP53 gene, responsible for lung cancer, was developed using a surface plasmon resonance (SPR) and a quartz crystal microbalance (QCM) biosensor systems. Amine coupling was employed for the immobilization of NeutrAvidin on thiol-derivatized surface to capture the biotinylated target sequence. Two targets sequences and one control DNA sequence were investigated including, a fully complementary (30 mer), one-point mutation and a non-complimentary DNA using hybridization with a detection probe strand (27 mer). The most appropriate surface coating was also examined for both sensor platforms with hybridization and single nucleotide polymorphism (SNP) detection efficiency were then compare. A 0.03-2 μM concentration range of detection probe was detected using the SPR and QCM sensors on wild and mutant type target surfaces. The linear regression analysis was performed for both sensors resulting in a R 2 value for the SPR assay of 0.985 and 0.993 for perfect and mismatch reaction and of 0.978 and 0.976 for the QCM assay, respectively. The obtained results demonstrate that the used approach represents a very promising future method for the detection of one-point mutation in genetic-based health problem with highly sensitive, specific, and real-time analysi

Surface plasmon resonance based immunosensor for the detection of the cancer biomarker carcinoembryonic antigen

An immunoassay in optimised conditions with a highly sensitive surface plasmon resonance (SPR) based biosensor was developed for the detection of the cancer biomarker carcinoembryonic antigen (CEA). Different formats of the immunoassay were initially investigated on the surface of the gold sensor chip. A self- assembled monolayer (SAM) was formed on the gold chip using 11- mercaptoundecanoic acid (MUDA), before the immobilisation of the antibodies was conducted. The assay was then formed in a direct capture and a sandwich assay. In order to increase the sensor signal the CEA antigen was incubated with the detection/capture antibody before it was injected to the sensor chip surface and the results were recorded in real-time using the Biacore 3000 instrument. A detection limit of 3ngml-1 CEA was obtained with a dynamic detection range from 3ngml-1 to 400ngml-1 with correlation coefficients of 1.00 and 0.99 for the sandwich and rabbit anti-mouse (RAM) capture assay. Kinetic data analysis was performed for the standard capture test and subsequently for the developed assays and Rmax showed an increase from 215 RU for the standard capture test to 428 RU for the RAM-capture assay and 734 RU for the sandwich assay, respectively. The developed SPR immunosensor using the sandwich assay format showed high sensitivity and reproducibility for CEA detection which makes it a promising procedure for cancer biomarker analysi

The British Role in Appearence of Armenian Problem According to Ottoman Archive Records Until 1890

Osmanlı Devleti’nin güç kaybetmeye başlamasıyla birlikte toprak kaybetmesi, büyük devletler olarak nitelendirilen İngiltere, Fransa ve Rusya’nın başı çektiği pek çok devletin İmparatorluğun topraklarından pay kapma, bunun mümkün olmadığı durumlarda da zamanın güç dengeleri çerçevesinde rakip devletlerin bu topraklardan pay kapmasına engel olma siyaseti izlemelerine neden olmuştur. Büyük devletlerin en başta geleni ise o dönemde İngiltere’dir. İngiltere, Rusya’nın 1774 Küçük Kaynarca Antlaşması’nda elde etmiş olduğu, Ortodoks Hıristiyan tebaanın koruyucusu unvânına da dayalı olarak Yunan bağımsızlık harekâtını destekleyerek Doğu Akdeniz’de İngiltere’nin tarihi Hindistan yolunu tehdit eder bir pozisyonu yakalamasından son derece rahatsız olmuştur. Ayrıca, Rusların kendi topraklarında 1829-1830’larda kurdukları küçük Ermenistan bölgesini, Osmanlı Devleti aleyhine güneye doğru genişleterek sıcak denizlere inme, Kafkaslardan Doğu Anadolu’ya ve Basra ile İskenderun Körfezlerine inerek bir Ermeni toprağı yaratma plânları, İngiltere’nin bu bölgelerde yaşayan Ermenilerle ilgilenmesini kendi menfaatleri açısından zarurî kılmıştır. İngiltere, bu nedenle öncelikle Protestan Ermeni Cemaati varlığını ortaya çıkararak bunların Osmanlı Millet Sistemi içinde yer almasını sağlamıştır. Osmanlı Devleti’nin Berlin Antlaşması’nı imzalamak zorunda kalması ve bu Antlaşmada Ermenilerin haklarıyla ilgili taahhüt altına girmesi, İngiltere’nin de taraflardan biri olması, İngiltere’nin Ermeniler konusunda daha aktif hale gelmesini temin etmiştir. Bölgede bulunan konsolosları vasıtasıyla Ermeniler konusunda, Osmanlı Devleti’ne sürekli müdahale etmiş, Batı’da Ermeni sorununun ortaya çıkmasında, kamuoyu oluşturulmasında, maddî ve manevî desteğini esirgememiş, isyancı Ermenilere her türlü desteği vermiştir.The group of countries leaded by France, England and Russia were trying to get their share when possible or otherwise avoid other countries to get what they want after the Ottoman Empire start loose both power and land. After Russians gained the orthodox christians guardian position through Küçük Kaynarca Agreement in 1774 and their support to Greek Independence movement threatened the British interest in the Eastern Mediternian which was their historical Indian route. Especially Russian move to establish a small Armenian region in 1829-1830’s and to expand this region toward South with main interest to reach hot seas and Caucasia to Eastern Anotolia and to Persian Gulf disturbed England. As a first move, England created a protestantArmenian group and placed them into the Ottoman National System. After the Ottoman Empire had signed Berlin Agreement which included promises about the Armenians caused England to actively involve constantly in related with Armenian issues through their consulates in the region. Besides their involvement in this issue, they also supported them in rising the Armenian problem in west both with money and publicizing the problem in press. They also supported the fighting Armenian Commitas

The British Role in Appearence of Armenian Problem According to Ottoman Archive Records Until 1890

Osmanlı Devleti’nin güç kaybetmeye başlamasıyla birlikte toprak kaybetmesi, büyük devletler olarak nitelendirilen İngiltere, Fransa ve Rusya’nın başı çektiği pek çok devletin İmparatorluğun topraklarından pay kapma, bunun mümkün olmadığı durumlarda da zamanın güç dengeleri çerçevesinde rakip devletlerin bu topraklardan pay kapmasına engel olma siyaseti izlemelerine neden olmuştur. Büyük devletlerin en başta geleni ise o dönemde İngiltere’dir. İngiltere, Rusya’nın 1774 Küçük Kaynarca Antlaşması’nda elde etmiş olduğu, Ortodoks Hıristiyan tebaanın koruyucusu unvânına da dayalı olarak Yunan bağımsızlık harekâtını destekleyerek Doğu Akdeniz’de İngiltere’nin tarihi Hindistan yolunu tehdit eder bir pozisyonu yakalamasından son derece rahatsız olmuştur. Ayrıca, Rusların kendi topraklarında 1829-1830’larda kurdukları küçük Ermenistan bölgesini, Osmanlı Devleti aleyhine güneye doğru genişleterek sıcak denizlere inme, Kafkaslardan Doğu Anadolu’ya ve Basra ile İskenderun Körfezlerine inerek bir Ermeni toprağı yaratma plânları, İngiltere’nin bu bölgelerde yaşayan Ermenilerle ilgilenmesini kendi menfaatleri açısından zarurî kılmıştır. İngiltere, bu nedenle öncelikle Protestan Ermeni Cemaati varlığını ortaya çıkararak bunların Osmanlı Millet Sistemi içinde yer almasını sağlamıştır. Osmanlı Devleti’nin Berlin Antlaşması’nı imzalamak zorunda kalması ve bu Antlaşmada Ermenilerin haklarıyla ilgili taahhüt altına girmesi, İngiltere’nin de taraflardan biri olması, İngiltere’nin Ermeniler konusunda daha aktif hale gelmesini temin etmiştir. Bölgede bulunan konsolosları vasıtasıyla Ermeniler konusunda, Osmanlı Devleti’ne sürekli müdahale etmiş, Batı’da Ermeni sorununun ortaya çıkmasında, kamuoyu oluşturulmasında, maddî ve manevî desteğini esirgememiş, isyancı Ermenilere her türlü desteği vermiştir.The group of countries leaded by France, England and Russia were trying to get their share when possible or otherwise avoid other countries to get what they want after the Ottoman Empire start loose both power and land. After Russians gained the orthodox christians guardian position through Küçük Kaynarca Agreement in 1774 and their support to Greek Independence movement threatened the British interest in the Eastern Mediternian which was their historical Indian route. Especially Russian move to establish a small Armenian region in 1829-1830’s and to expand this region toward South with main interest to reach hot seas and Caucasia to Eastern Anotolia and to Persian Gulf disturbed England. As a first move, England created a protestantArmenian group and placed them into the Ottoman National System. After the Ottoman Empire had signed Berlin Agreement which included promises about the Armenians caused England to actively involve constantly in related with Armenian issues through their consulates in the region. Besides their involvement in this issue, they also supported them in rising the Armenian problem in west both with money and publicizing the problem in press. They also supported the fighting Armenian Commitas

Diabetik sıçanlarda malign serebral iskemi ve iskemik ön koşullanmanın epigenetik rolünün araştırılması.

Objectives: In this study, we aimed to evaluate the effect of the Ischemic preconditioning (IPreC) on the expression profile of cerebral miRNAs against stroke by induced transient middle cerebral artery occlusion (MCAo) in diabetic rats

Gold nanoparticle modified capacitive sensor platform for multiple marker detection

The detection and quantification of cancer biomarkers in human blood is crucial to diagnose patients in the early stage of a disease. The recent advances in biosensor technology can improve detection by reducing the application time and cost without an invasive approach. In this study, a highly sensitive, novel nanoparticle-modified capacitive sensor was developed for the detection of cancer markers. The current work mainly focused on developing a surface modification protocol for achieving higher sensitivity using Au-NPs. An interdigitated electrode (IDE) transducer was modified using gold nanoparticles (Au-NPs) for signal enhancement, the platform was initially optimized with a small size IL-6 protein and the methodology was then applied for multiple marker detection with the aim of precise disease diagnostics. Carcinoembryonic antigen (CEA) and epidermal growth factor receptor (hEGFR) could be successfully detected in the concentration range of 20–1000 pg mL−1 while cancer antigen 15-3 (CA15-3) was detected in the range of 10–200 U mL−1. These results show an increase of sensitivity by five-fold with respect to those not modified, demonstrating a highly sensitive and specific capacitive immunoassay that has a great potential for the use of early diagnosis of cancer disease

A novel magnetic particle-modified electrochemical sensor for immunosensor applications

In this study, a novel magnetic particle-modified capacitive sensor was reported for the detection of cancer markers. A gold interdigitated (GID) capacitor transducer was modified using magnetic beads (MB) for signal enhancement and the optimal frequency range and magnetic bead amount were determined. The platform was initially tested using C-reactive protein (CRP) as the model analyte and the methodology was then transferred for multiple marker detection with the aim of precise disease diagnostics. For the first time, the protein biomarkers of lung cancer including carcinoembryonic antigen (CEA), epidermal growth factor receptor (hEGFR) and cancer antigen 15-3 (CA15-3) were investigated with a capacitive sensor. The threshold levels of the markers to indicate the cancer are higher than 5 ng mL−1 (CEA), 64 ng mL−1 (hEGFR) and 50 U mL−1 (CA15-3), respectively. CEA and hEGFR could successfully be detected in the concentration range of 5 pg mL−1 to 1 ng mL−1 while CA15-3 was detected in the range of 1–200 U mL−1 with a high specificity. Our study demonstrates a highly specific capacitive immunoassay, presenting a potential alternative tool for early and precise diagnosis of cancer disease

A new microfluidics system with a hand-operated, on-chip actuator for immunosensor applications

This paper presents the realization of a portable, point-of-care and multi-target immunosensing lab-on-a-chip (LOC). The chip utilizes a novel on-chip actuating mechanism which uses a negative pressure to create thrust inside the channels to facilitate and control the fluid flow. No external instruments and/or sources were used to drive or control the liquid throughout the experimentation. LOC demonstrates a highly sensitive detection and quantification of a cancer marker, human-epidermal growth factor receptor (hEGFR) and a cardiac marker, interleukin 6 (IL-6) by impedimetric measurement approach. Without the use of any signal amplification methods (chemical), a dynamic detection limit of 3-8 ng/ml of hEGFR and 0.1-5 ng/ml of IL-6 in human serum was obtained. The extracted dissociation constants were calculated as 5.86 ng/ml (hEGFR) and 2.45 ng/ml (IL-6) by kinetic analysis