Prostat Kanseri Biyobelirteçlerinin Tayini İçin Nanoplazmonik Platformların Hassasiyetinin Arttırılması
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ABSTRACT ENHANCING THE SENSITIVITY OF NANOPLASMONIC PLATFORMS FOR DETECTING PROSTATE CANCER BIOMARKERS Semih ÇALAMAK Doctor of Philosophy, Department of Nanotechnology and Nanomedicine Supervisor: Prof. Dr. Kezban ULUBAYRAM JUNE 2018, 148 pages Early detection of cancer biomarkers in body fluids has significant importance for early diagnosis of cancer. LSPR technologies are the most powerful optical biosensors that can be used for label-free detection of biomolecules at ultra-low concentrations (ag/mL). Despite these advantages, the detection limits for many biomolecules are not at the desired levels. Especially biomarkers with low molecular weight can not be detected with LSPR sensors. The aim of the thesis is to develop the easy and cost-effective way to improve the sensitivity of nanoplasmonic platforms to detect low molecular weight biomarkers with enhanced plasmon coupling and in-situ gold nanoparticle growth method under static and dynamic conditions (in microfluidic platforms). In the first part of the thesis theoretical analysis of the electric field interactions of gold nanoparticles were investigated to determine the most suitable gold nanoparticle size and configurations for more precise measurement. The electric field enhancements on gold nanoparticles (20, 50, 80 and 100 nm) were investigated using Mie theory and the highest electric field enhancement was observed on the gold nanoparticle, which has the size of 50 nm. After that, double, triple and quadruple gold nanoparticle (50 nm) arrays were assembled and the highest electric field enhancement was calculated for quadruple nanoparticle array with 40.85 V/m electric field and 11.10 electric field enhancement factor. In the second part of the thesis, gold nanoparticles were functionalized on PS surface via polyethyleneimine (PEI). It was found that the nanoplasmonic iv surfaces showed the sharpest LSPR signal on the PS surfaces modified with 1 mg/mL PEI at 548 ± 1.5 nm maximum wavelength. In the third part of the thesis, a cost-effective new approach has been developed to increase the sensitivity of nanoplasmonic platforms. In this new approach, gold nanoparticles which were functionalized on PS surface were grown (in-situ) under static and dynamic (laminar and dynamic flow) using microfluidic platforms. In microfluidic chips with laminar and turbulence flow regimes, gold nanoparticles were grown more homogeneously and single row sequences on PS surface with increasing LSPR signal. Gold nanoparticles, which have 50 nm of particle size reached 110 ± 14, 123 ± 12 and 175 ± 6 average particle size in static media, laminar flow, and turbulence flow media after in-situ particle growth, respectively. The maximum wavelengths of nanoplasmonic surfaces were shown red shifts from 548 ± 4 nm to 569 ± 3, 570 ± 2 and 577 ± 4 nm for static in-situ, laminar in-situ and turbulence in-situ nanoplazmonik surfaces, respectively. Furthermore, after in-situ particle growth, turbulence in-situ nanoplasmonic surfaces showed significant red shifts in maximum wavelength along with an increase in extinction intensity in the LSPR signals three times more compared to the standard nanoplasmonic surface. In the last part of the study, detection studies of prostate cancer biomarkers (BSA (66 kDa), TGF-β1 (12.8 kDa) and BMP-2 (13 kDa)) with various molecular weights were carried out on standard, static in-situ and turbulent in-situ nanoplasmonic surfaces. Turbulent insitu nanoplasmonic surfaces were found more sensitive than standard nanoplasmonic surfaces and static in-situ nanoplasmonic surfaces from 1 pg/mL concentration of high (BSA) and low molecular weight (TGF-β1 and BMP-2) prostate cancer biomarkers. These results have shown that the nanoplasmonic platforms integrated into the microchips are reliable, accurate, reproducible and applicable.