Effects of sampling rate on the interpretation of cellular transport measurements

Electrochemical sensing techniques are increasingly used to study biological processes by monitoring concentration changes of the molecule of interest close to cells. The measured concentration is the result of cellular transport across the cell membrane and diffusion of the released molecules from the cells to the sensing electrode. The objective of such experiments is to understand the cellular processes underlying the observed changes in concentration. Thus, the influence of mass transport on the measured concentration trace has to be removed. This is done by deconvolution of the impulse response function of diffusion from the concentration data. We have recently observed that measuring concentration at a sampling rate that satisfies the Nyquist criterion for the observed concentration dynamics may not be sufficient to correctly reconstruct cellular flux. This is because the impulse response function of diffusion also has to be represented with sufficient temporal resolution. We discuss this problem here using the example of monitoring drug efflux from a monolayer of cancer cells with microvoltammetry, and chloride secretion from an epithelial cell monolayer monitored with an ion-selective electrode.