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This paper reports on a sensing mechanism created by converting a change in solid–liquid interfacial tension due to molecular interactions into a change in capillary force loading for a cantilever sensor design. Compared with former cantilever sensor designs based on surface stress measurement, the proposed mechanism takes advantage of capillary force to effectively amplify the signal output of the sensor by several orders of magnitude. A complementary-metal-oxide-semiconductor-based cantilever sensor design validates the proposed sensing mechanism. Detection of Biotin-NeutrAvidin specific binding in picomolar sample concentrations was demonstrated for the application of biochemical assay.