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TOXicity assessment on neurons and cardiomyocytes by means of FluoRescence Emitting Electrodes

Periodic Reporting for period 1 - TOX-Free (TOXicity assessment on neurons and cardiomyocytes by means of FluoRescence Emitting Electrodes)

Okres sprawozdawczy: 2021-06-01 do 2022-05-31

Drugs, pesticides and chemical pollutants can potentially cause neurotoxicity and cardiotoxicity. However, we lack robust assays for accurate and sensitive assessment of functional toxicity in the cardiac and central nervous systems. The EU-funded TOX-Free project develops a non-invasive nanotechnology-based technique capable of recording in vitro electrical signals from human stem-cell derived neuronal and cardiac cells. The TOX-Free biosensing technology is based on the "VIrtual CEll" (VICE) concept that transduces electrophysiological activity into optical signals in a label-free way (A. Barbaglia, Advanced Materials, 2021). The VICE biosensor will allow the assessment and quantification of subtle cellular and functional disturbances by toxicants or drugs beyond existing technologies including microelectrode array (MEA) and live-cell imaging. The biosensor will find direct applications in toxicology and pharmacology as well as in basic biology studies.
During Reporting Period 1 (first 12 months of the project, RP1), the partners have focused their technical efforts primarily toward (i) the realization of VICE 1.0 (first version of the TOX-Free biosensor), (ii) the preparation of all experimental setups in partner’s labs for testing the VICE biosensor, (iii) the preparation of a suitable software bench for Acquisition and analysis, and (iv) surface modifications of the biosensor for improvement of cell culture conditions.
The consortium has been active on communication, dissemination, and exploitation activities. TOX-Free has been presented online and in-person during several events, on social media, and in four peer-reviewed scientific publications.
A first market analysis has been commissioned to an external consultant, who assessed the overall potential market in which TOX-Free could be exploited, i.e. toxicology assessment by mean of fluorescence microscopy.
The VICE biosensor of TOX-Free will be the first device for recording neuronal and cardiac action potentials in-vitro in a completely non-invasive manner. It will allow for detecting subtle toxic effects on neurons and cardiomyocytes caused by drugs, pollutants, toxicants and other foreign molecules. Thanks to the non-invasiveness of the measurement, cells will be monitored for long time for assessing long-term and chronic toxic effects. Such features are beyond the state of the art represented by patch-clamp, microelectrode arrays, and calcium imaging, as all these traditional techniques cannot measure accurately action potentials without affecting cell health in long-term experiments.
The possibility to monitor toxic effects in long-term screenings will be fundamental to assess in-vitro toxicities that ofter remain hidden to standard tests. On the one hand, this will reduce the need of in-vivo tests on animals or during clinical phases. On the other hand, long-term screenings may shed light on previously unknown toxic effects of molecules that need to be withdrawn from the market or from which the population must be protected.
Fluorescence imaging of cardiac cells on a VICE biosensor