Tailoring the Sensitivity of Microcantilevers To Monitor the Mass of Single Adherent Living Cells

Microcantilevers are widely employed as mass sensors for biological samples, from single molecules to single cells. However, the accurate mass quantification of living adherent cells is impaired by the microcantilever's mass sensitivity and cell migration, both of which can lead to detect masses mismatching by ≫50%. Here, we design photothermally actuated microcantilevers to optimize the accuracy of cell mass measurements. By reducing the inertial mass of the microcantilever using a focused ion beam, we considerably increase its mass sensitivity, which is validated by finite element analysis and experimentally by gelatin microbeads. The improved microcantilevers allow us to instantly monitor at much improved accuracy the mass of both living HeLa cells and mouse fibroblasts adhering to different substrates. Finally, we show that the improved cantilever design favorably restricts cell migration and thus reduces the large measurement errors associated with this effect.