This paper presents numerical analysis of an in-plane resonant nano-electro-mechanical (NEM) sensor based on mass-detection principle using a 3D FEM electromechanical simulation combined with a NEM/MOS hybrid circuit simulation. The self-assembled linker molecules are modeled simply by adding extra surface coating layer, and three different functionalization schemes are studied: top and bottom, only top and all-around configurations. We investigate the impacts of the coating layer mass change as well as stiffness change on the resonance frequency by varying thickness of the coating layer for all the configurations. The small signal AC analysis of the sensor is performed, and the effect of the coating layer on the output signal is studied. Mass of the coating layer is then changed in order to model the random adsorption of target molecules onto the coating layer surface. We show that the NEM sensor enables to achieve the mass responsivity of 0.05 zeptogram/Hz for all the different functionalization schemes, which is approximately 11 orders smaller than that reported for present quartz crystal microbalance sensors. Moreover, we clarify that the scaling rule of the mass responsivity is given by k(4) regardless of the different functionalization configurations. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.