We report a membrane-based chemomechanical transducer for the sensitive detection of surface molecular reaction through a highly reliable common mode rejection (CMR) technique. Chemomechanical transduction, originally based on the micro-cantilever, offers potential benefits: label-free assay, and real-time monitoring of molecular interaction via mechanical deformation [1, 2]. Membrane-based approaches have been proposed to overcome the inherent limitations of the micro-cantilever system, but most results were either inconclusive or far from practical standards. Here we show clear-cut detection of molecular binding using a membrane transducer fabricated with conventional MEMS technology. This goal is achieved through the implementation of CMR that rejects physical effects such as pressure and temperature, leaving only specific chemical binding responsible for resulting signal. We demonstrate highly specific recognition of thrombin protein by using DNA aptamer immobilized on the membrane surface with the limit of detection down to ~3 pM, and the wide dynamic range > 5×10 4 .