Piezoresistive cantilevers have been extensively used for many years as force sensors, mass detectors, image scanning tools, and as biosensors, which have absorbate layers generating surface stress upon reaction with analyte. We will introduce different piezoresistive biosensor designs, e.g., single clamped cantilever and membrane-type sensor. The different sensor structures are compared with respect to DR/R value of a single piezoresistor embedded on the device structures with different arrangements. The quantitative DR/R values of each sensor were calculated with a simulation tool based on finite element analysis, to be introduced as another contribution to this conference. Based on the results, we will present an optimized single clamped cantilever with one piezoresistor and an optimized biosensor structure, which is not a simple “cantilever” rather it consists of an “absorbate membrane” suspended by four “sensing beams”.