Nonlinear dielectric spectroscopy for label-free detection of respiratory activity in whole cells

We report on a novel electromagnetic biosensing technique for detecting respiratory activity in whole cells suspended in aqueous solution. Application of a pure sinusoidal voltage between two outer electrodes applies an oscillatory electric field to the aqueous cell suspension at frequencies in the range of one to several kHz. The fundamental and higher order harmonic responses are measured across two inner electrodes using a dynamic signal analyzer. Aqueous suspensions of S. cerevisiae (budding yeast), with both active and inactive mitochondrial electron transport (respiratory) chains are employed for this study. We find that the measured third harmonic for certain frequency ranges shows significant temporal changes in actively respiring yeast, while little significant changes are observed in yeast with suppressed respiratory activity, i.e. mutant yeast strains or yeast in the presence of respiratory inhibitors. The method holds potential for further development to detect respiratory activity in live tissue in vitro and perhaps in vivo for clinical applications.