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This paper considers mechanical stress and strain in a piezoresistive cantilever sensor under surface stress loading, which is the loading condition that occurs in biochemical sensing applications. Finite element simulations examine the piezoresistor sensitivity due to changes in cantilever length, width, and thickness, and piezoresistor size, location, and depth. A few unexpected results are found. Unlike cantilevers designed for atomic force microscopy, cantilevers for biochemical sensing should be short and wide. While shallow piezoresistors offer good sensitivity, the piezoresistor may extend far into the thickness of the cantilever and still be quite effective. The paper concludes with comments on design guidelines for piezoresistive cantilever sensors.