We theoretically investigate the dependence of the different parameters of an optical biosensor for the detection of Hydrogen peroxide (H 2O 2) based on absorption enhancement of Cytochrome c molecules near gold nanoparticles. H 2O 2 is a major reactive oxygen species which is involved in signaling pathways and oxidative stress in cells. We use the Green's function approach as well as confirm the corresponding simulation results using the surface integral formulation. Further we show that this technique can be applied for detection of other small molecules, like oxygen and carbon monoxide. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).