Label-free monitoring of cell-based assays: combining impedance analysis with SPR for multiparametric cell profiling.

Label-free approaches to monitor cell-based assays provide an unprecedented, time-resolved and non-invasive view on the response of mammalian cells to chemical, biological or physical stimuli. The most widespread techniques are impedance analysis and optical sensing using evanescent waves like SPR. This study describes the combination of both in one experimental setup so that a given cell population can be monitored simultaneously for electrical and optical changes. The device is based on commercial SPR chips that are processed by photolithography to provide electrodes for impedance analysis and gold spots for surface plasmon excitation on the same substrate. Simultaneous recordings do not interfere with each other but provide independent, time-resolved information on cell shape changes (impedance) and dynamic mass redistribution (SPR) as they occur during exposure of the cells to drugs or toxins or along their normal life cycle. This study provides proof-of-concept experiments of the dual biosensor platform in two experimental settings: signals are recorded and analyzed (i) during cell attachment, spreading and differentiation of initially suspended cells and (ii) during the exposure of the mature cells to an actin cytoskeleton disrupting drug. Impedance and SPR recordings provide complementary information that can be used to trace and assign intracellular mechanisms of action.