FishOnChip project proposes to use a microfluidic multi-chamber microchip (MIMUC) coupled to a NanoporousElectrode Array (NEAR) chip able to measure transcriptomic responses resulting from multi-cell interactions mimicking toxicokinetic and toxicodynamic processes occurring in the MIMUC.
FishOnChip project aims to use a microfluidic multi-chamber microchip (MIMUC) coupled to a NanoporousElectrode Array (NEAR) chip able to measure transcriptomic responses resulting from multi-cell interactions mimicking toxicokinetic and toxicodynamic processes occurring in the MIMUC. The MIMUC will include different fish cell lines, mimicking the physiological connections between different tissues implicated in the toxicant uptake (gills, gut), the xenobiotic metabolism in liver, and the toxic effects on reproductive organs. Following exposures, selected transcriptomic responses will be measured using a NEAR chip obtained by merging the high throughput multiplexing capacity of microelectrode arrays with the unmet sensitivity of nano- biosensors, functionalized with custom cDNA probes for direct mRNA detection. This will allow for a risk assessment of chemicals based on transcriptomic responses of key genes linked to molecular initiating and key events selected across existing adverse outcome pathways (AOPs). We will first develop a simple MIMUC and the NEAR chip technology as a proof-of-concept, that could be scalable to more complex devices incorporating multi cell culture layers, 3D cell cultures and denser electrode arrays. Transcriptomic effects will be complemented with cell hallmarks of toxicity linked to cell viability, proliferation (growth) and reproduction. Validation of cell-based responses will be based on in silico analyses of existing AOPs, for specific reproductive effects using the placenta cell line JEG-3 – an established endocrine model, and for some mode of actions using Daphnia magna toxicogenomic assays.
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