Göz yüzeyinden in vivo metabolomiks çalışmaları için kullanılabilecek lens şeklinde tasarlanmış invazif olmayan ve biyo-uyumlu mikroekstraksiyon ince filmlerinin geliştirilmesi

In this thesis, the aim was to develop biocompatible extractive thin films in contact lens geometries with application potential for in vivo sampling of small molecules from the eye surface with the ultimate goal of being suitable for untargeted metabolomics and biomarker discoveries. For the purpose of the study, polydimethylsiloxane was functionalized with amine-containing groups using in situ modification approach and thin films were characterized with Fourier transform infrared spectroscopy, energy dispersive x-ray analysis, thermogravimetric analysis, and contact angle measurements. To investigate the thin films under representative conditions of eye surface contact lens geometries and in vitro agarose gel eye model were prepared in 3D printed molds To investigate the extractive capabilities of the thin films, various metabolites found on the eye surface such as representative lipids, amino acids, and neurotransmitters were used. Extractive capabilities of modified and unmodified polydimethylsiloxane thin films were compared by extractions from aqueous solutions and in vitro eye models after separation and detection of the analytes with liquid chromatography/mass spectrometry. Extractions showed that modified extractive lenses had between 60 to 130% increased extractive capability towards polar analytes and similar extractive capability towards non-polar analytes compared to unmodified polydimethylsiloxane extractive lenses. Composition of the desorption solvent and desorption time were optimized as ACN:MeOH:H2O (40:40:20, v/v/v/) and 30 minutes, respectively. Extractions using modified extractive lenses from the agarose in vitro eye model showed good repeatability with RSD% values ranging between 5 to 18% and good linearity in the tested range of 50.0-500.0 ng mL-1 for all analytes.