Quantitation of cell dynamics is a prerequisite for challenging biosensing and biomedical applications, ranging from cancer progression and metastatic potential evaluation, to assessment of cytopathic effects. Targeting fast label-free retrieval of electrical and optical parameters of cell-cell, cell surface interaction dynamics and of the temporal nanometer-scale fluctuations, we advance a novel concept of a multimodal, label free, functional imaging instrument. We report on ways to exploit the AC electrical modulation of the refractive index of a tailored (sensing) interfaces, e.g. custom designed conductive microscope slides, via an externally applied AC voltage, and time lapse optical assays to provide label free contrast of the local electrical impedances and surface charge densities - beyond the limitations of standard electrode-based technologies. This enables high content assessment of single cell relevant biophysical parameters and of their dynamics as well as of cellular fluctuation profiles. The concept grounds a wide range of electrically-modulated optical assays for measuring the electric field locally at nanoscale including quantitative phase microscopy or reflected light microscopy. The virtues of this novel enabling tool to monitor intracellular trafficking and electrical impedance contrasts and dynamical cellular response in living cells include: quantitative assessment of cytopathic effect (evaluation of relevance for viral infection), cell signaling, drug screening and hazard evaluation (e.g. last resort antibiotics, toxic compounds).
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