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As a natural living system, mammalian cells have the ability to respond to various environmental cues in
distinct ways at both the cellular and molecule levels. Such unique ability of the cells can be utilized for the
rapid detection of chemical and biological analytes. In this report, we have demonstrated the feasibility of a novel cell-based biosensor that utilizes a microcantilever to convert a cellular response to a measurable mechanical response. With this innovative approach, we have been able to detect the distinct responses of α-cyclodextrin and methyl-β-cyclodextrin with mammalian cells based on their differential effects on cells. This study has established a foundation for the future development of a highly sensitive sensing platform for environmental, medical, toxicological, and defense applications.