Design, preparation, and study of physicochemical properties of molecular assemblies are extremely challenging multidisciplinary research fields. Understanding the elementary principles that correlate these properties with molecular level of electronic behavior will enable us to control basic properties of molecule-based compounds as well as of classical semiconductors. In particular, chemical modification of field effect sensor devices where the metal gate is replaced with organic molecular layer, projects a crucial impact upon the electrical properties of the sensor. In these cases it is important to control the effects in order to ensure that the organic gate is optimized for sensing. Here we used fully depleted silicon-on-insulator (SOI) ion sensitive field effect transistor in order to analyze the projection of surface chemical modification on electronic performance. We suggest that surface activation and the application of 3-aminopropyltrimethoxysilane on top of the gate dielectric introduces negative charge at the Si/ SiO2 interface or/and on top of the gate dielectric and consequently an accumulation layer that confines the electrons to the bottom of the SOI channel. The transistor gain postmodification is characteristic of volume inversion, and therefore suggests that, following modification, the channel electrons are confined to SOI thickness of <10 nm. Finally, measurements of pH sensitivity indicate that the pH sensitivity post- UV/ O3 treatment is maximized suggesting that the negative charge is introduced during the activation process, where the density of the negatively charged amphoteric sites maximized.