MEMS mass sensors with uniform sensitivity for monitoring cellular apoptosis

Abstract

MEMS-based resonant mass sensors can be sensitive tools to measure the physical properties of cells such as their mass. We recently developed an array of sensors that have a uniform mass sensitivity for measuring the stiffness and the long-term growth rate of adherent human colon adenocarcinoma cells (HT-29) [1]. We demonstrated that for these adherent single cells, the cell growth rate increases with call mass, i.e. larger cells grow faster. The finding points to the fact that additional cell-size control mechanisms might be required for cell size homeostasis over generations and that growth rate is determined by the amount of the ribosomal machinery, which doubles during the cell cycle. Here, we expand our studies by presenting an additional sensor design with further optimization for higher uniformity of the mass sensitivity based on a detailed numerical analysis. We also demonstrate that MEMS resonant mass sensors can be used to measure physical changes in apoptotic cells. HT29 were treated with staurosporine, a potent drug that induces cellular apoptosis. Through Laser Doppler Vibrometery (LDV), we measured changes in the cells' apparent mass, and correlated these changes with optical images using dark field microscopy. Such real-time mass measurements of individual cells coupled with optical imaging can be a powerful tool to understand the physiological processes of cell growth and apoptosis.