Measuring mass changes in single suspended and adherent cells, with applications to personalized medicine in Glioblastoma Multiforme (GBM)

Abstract

The increased precision offered by developments in suspended microchannel resonator (SMR) technology opens the possibility for measuring small mass changes in cells. Mass accumulation rate (MAR) measurements in single suspended cells over short periods of time have the potential for characterizing heterogeneous collections of tumorigenic cells and serve as a functional marker for the effects of anti-cancer drugs. In this thesis we adapt mass accumulation measurements for use in Glioblastoma Multiforme (GBM) patient-derived cell lines, exploring the heterogeneity between and within patient tumors, and validating the measurement as a predictor of drug susceptibility with response times on the order of 24 to 48 hours using an experimental MDM2 inhibitor. While MAR measurements can be performed on suspended single cells with high precision, it has not yet been adapted for measuring the growth of adherent cells. We develop a technique to measure mass accumulation in cells adhered to the inner surface of the resonator channel. To overcome challenges inherent in such a measurement, we use infrared imaging and multiple resonant modes to reveal the cell's position in the SMR, and utilize differential measurements from a second cantilever to account for frequency drift.