Integrating impedance-based growth-rate monitoring into a microfluidic cell culture platform for live-cell microscopy

Growth rate is a widely studied parameter for various cell-based biological studies.Growth rates of cell populations can be monitored in chemostats and micro-chemostats,where nutrients are continuously replenished.Here,we present an integrated microfluidic platform that enables long-term culturing of non-adherent cells as well as parallel and mutually independent continuous monitoring of(i)growth rates of cells by means of impedance measurements and of(ii)specific other cellular events by means of high-resolution optical or fluorescence microscopy.Yeast colonies were grown in a monolayer under culturing pads,which enabled high-resolution microscopy,as all cells were in the same focal plane.Upon cell growth and division,cells leaving the culturing area passed over a pair of electrodes and were counted through impedance measurements.The impedance data could then be used to directly determine the growth rates of the cells in the culturing area.The integration of multiple culturing chambers with sensing electrodes enabled multiplexed long-term monitoring of growth rates of different yeast strains in parallel.As a demonstration,we modulated the growth rates of engineered yeast strains using calcium.The results indicated that impedance measurements provide a label-free readout method to continuously monitor the changes in the growth rates of the cells without compromising high-resolution optical imaging of single cells.