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This chapter presents the design, modeling, fabrication, and characterization of in-plane resonant nano-electromechanical (NEM) sensors based on mass detection principle. The simplified NEM sensor consists of a clamped-clamped (CC) beam with two side electrodes, in-plane resonant NEM (IP-RNEM) sensor. Later, the IP-RNEM sensor is monolithically integrated with an in-plane field-effect-transistor (FET) to realize the in-plane resonant suspended gate FET (IP-RSGFET) sensor. The numerical modeling of IP-RSGFET sensor is presented using a three-dimensional finite-element-method electromechanical simulation of IP-RNEM sensor combined with a NEM-MOS hybrid circuit simulation. We investigate the impacts of the adsorbed self-assembled linker and target molecules in various configurations on the resonance frequency of the sensor that results in the mass responsivity of 0.05 zepto g/Hz for all the different functionalization schemes, which is approximately 11 orders of magnitude smaller than that of the reported value for present quartz crystal microbalance sensors. A comparison is shown for the important parameters of the current mass detection-based sensors and the proposed NEM sensors. The effects of structural modification on the high-frequency characteristics are studied numerically for various key parameters of the sensor. Further modification and numerical analysis for the IP-RSGFET sensor are conducted to improve the DC characteristics of the sensor for the consequent RF measurement. The RF characterization of the IP-RNEM sensor is successfully conducted using a down-mixing measurement technique. The outcomes of the modeling and experimental analysis provide a realistic guideline for further improvement and characterization of these ultrasensitive sensors.