aThere is a great need to improve the biocompatibility of silicon-based lab-on-chip substrate materials for reliable quantitative analysis of biological solutions. These advanced microdevice surfaces need not only be biocompatible but also have surfaces of defined wettability characteristics. The inhibition of biomolecular activity due to microdevice surface interaction is common and can result in inaccurate results or decreased reaction yields. In this work we investigate different techniques for the chemical functionalization of oxidized silicon (SiO x ) surfaces in order to: (i) obtain defined hydrophobic/hydrophilic surfaces; and (ii) increase the efficiency of performing Real-Time Polymerase Chain Reaction (PCR) on a silicon-based lab-on-chip. Silicon oxide surfaces are functionalized by grafting alkylic chain silanes and poly(ethylene glycol) (PEG) chains to the surfaces, rendering them hydrophobic or hydrophilic. Functionalized surfaces are characterized through contact angle and atomic force microscopy (AFM) measurements, showing stable hydrophobic surfaces with contact angles of 69-78• and layer thicknesses of 11-15 Å and hydrophilic surfaces displaying contact angles of 5-6• and thicknesses of 22-52 Å. PCR experiments carried out directly on bare silicon oxide lab-on-chip surfaces show low yields of DNA amplification. Hydrophobic surfaces decrease the inhibition of PCR. Hydrophilic surfaces are a major improvement on the bare silicon oxide exhibiting the same maximum reaction yield as obtained with a standard thermocycler. We have found that the best results are associated with PEG modified surfaces, which prove very suitable for the fabrication of reliable PCR silicon lab-on-chips.