Abstract: Quantitation of cell dynamics is a prerequisite for demanding cell based biosensing applications related to cytotoxicity testing.
We take the challenge to advance a novel cellular sensing assay with boosted sensitivity and reproducibility for evaluating cytotoxicity of novel drugs and bio-materials. The dynamics of the: distribution of electro-optical cellular parameters (refractive index, and electrical conductivity), membrane permeability, cell-surface and cell-cell interaction were chosen as reporter processes. This work is connected with radically new support concepts recently developed associated with improved bio-sensing capability of dynamic control of electrified bio-interfaces’ response to an exogenous rhythm in cell-based platforms.
We present a multimodal, label free, high spatial resolution and low temporal noise functional imaging instrument enabling high resolution optical and electrochemical mapping - the latter beyond the limitations of electrode-based technologies (surface or scanning ones). It exploits the electrical modulation of the refractive index of a tailored (sensing) interface and of live cells, via an externally applied sinusoidal voltage to provide label free electric contrast of adhered and hydrogel matrix incorporated model eukaryotic cells. This enables high content label free assessment of cell parameters and is capable to provide electrical, morphological and structural properties of cellular structures dynamics relevant for toxicity evaluation.
We highlight the virtues and challenges of this novel opto-electrochemical method as an enabling tool for live cells analysis when undergoing toxic and cytopathic effects or in response to a model drug (a last resort antibiotic) presented as a case study.
The unique detection characteristics of this cellular platform are essential for applications in the fields of cell signalling, drug screening and hazard evaluation.
Reference support work US Patent US 11,680,939 B2; Anal. Chem, (2020), DOI: 10.1021/acs.analchem.9b03217; Light Sci Appl (2021) 10.1038/s41377-020-00461-x

Keywords: advanced cell based biosensing, label free electro-optical imaging, toxicity testing.

Acknowledgements: This research is supported by The Romanian Ministry for Education and Research, grant BioSense, PNRR-III-C9-2023-I8, contract CF129-31.07.2023.

Biography: Research Prof. Mihaela Gheorghiu is the head of the Biosensing Department of the International Centre of Biodynamics, Bucharest, Romania and PhD thesis advisor within the University of Bucharest (Biology Doctoral School). Physicist by formation, BSc Physics and MSc in Biophysics at the University of Bucharest (1994, and 1995 respectively), she obtained her PhD in 2003 and Habilitation in 2019 in Biology, University of Bucharest. She is the recipient of several fellowships such as of the Eastern Europe Research Scientists & Students Exchange & Collaboration Programme National University Singapore, at the Department of cell physiology, Catholic University Leuven, Belgium for postdoctoral stages, and of Boehringer Ingelheim, Research stage at Institute for Molecular Biotechnology, Jena, Germany, as well as of the Grigore Antipa Award of the Romanian Academy (in 2022). Her work combines engineering, modelling and biochemical tools for advancing electro-optical analytical platforms of cellular dynamics and of the effects triggered by various stimuli (as well as drug candidates) at single cell level. Prof Gheorghiu expertise covers the analysis of both homogenous and heterogenous cultures, encompassing prokaryotic (e.g., bacteria) and eukaryotic cells (including opto-genetically engineered ones).