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The authors have fabricated and tested all-optical micromechanical resonators that sense the presence of analyte molecules by monitoring the shift in the resonant frequency of a mechani-cal mode of vibration. An analysis of the measured frequency noise at the fundamental flexural mode shows that it is dominated by thermal-mechanical noise. This result demonstrates that thermal-mechanical frequency noise can set the limit of detection in actual micromechanical or nanomechanical resonance-based sensors.