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Sub-femtogram resolution of an in-liquid cavity optomechanical mass sensor based on the twin-microbottle glass resonator is demonstrated. An evaluation of the frequency stability using an optomechanical phase-locked loop reveals that this cavity optomechanical sensor has the highest mass resolution of g in water, which is four orders of magnitude better than that in our first-generation setup [Sci. Adv. 8, eabq2502 (2022)]. This highly sensitive mass sensor provides a free-access optomechanical probe in liquid and could thus be extended to a wide variety of in-situ chemical and biological metrology applications.

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