Work performed during Periods 1 & 2 (April 2016 to March 2019) is given under individual work packages. WP1 has synthesised 4 groups of NM: Au, SiO2, FexOy and TiO2. These NM were extensively characterised & sent out to all partners in the consortium. In addition Au and Ag NM of varying size, shape and functionality have been synthesised/characterised in particular to understand their interaction with the biomembrane module sensor element. WP2 has developed microfluidic networks and electronic systems for interfacing to the sensor element modules developed by individual partners. In particular a signal processing and data unscrambling algorithm has been successfully developed for analysing data generated by the biomembrane module. The biomembrane module has also been incorporated into an automated fluidic system which together with the electronic interrogation is entirely computer controlled. WP3 has identified strains of miRNA which are sensitive to NM damage. At the same time DNA-lipid conjugates have been incorporated into the biomembrane sensing element so that DNA damage can be electronically detected on-chip. WP4 has carried out a comprehensive study on interactions of novel NM with the biomembrane sensor element in the flow system. The lung-on-chip sensing device was initially configured and the single cell, liver-, kidney-, intestine- and placenta-on-chip devices have been developed together with their associated chip-based supports, flow systems and electronic/optical interrogation. WP5 has developed a 9 compartment PBPK model to mirror the experimental platforms. The model has been tested with published results on NM accumulation in in-vivo and in-vitro tissues and the fit to experimental data is good. WP6 has carried out 2 intercalibration exercises: Exercise (1) three soluble toxicants were sent out to 6 consortium partners. Results were extremely encouraging and showed that all sensor elements responded identically to the toxicity ranking of the toxicants. This can be explained by the fact that the cell/tissues sensor elements were recording membrane damage in their toxicity assay. Exercise (2) four groups of NM were sent out to the same partners. Results were less straightforward due probably to aggregation of the NM with time but they did show some consistency when this was taken into account. WP6 has continued with a general intercalibration of all platforms as well as performance characterisation/testing against the PBPK platform.
