Electronic monitoring of a 3D in vitro model of the renal tubule with integrated microfluidics

摘要

There is an urgent need to move away from using animal models for toxicological testing as well as pharmacological evaluation of chemical substances, driven both by societal distaste and also the large cost of using animals. The alternative to testing on animal models is the use of cell-based models in vitro. However, the validity and predictive ability of in vitro based models has been shown to be poor and results in significant failures of drugs with a high associated price-tag. Limitations in technology are a major factor in the failure of the cell-based models. We take advantage of recent advances in materials research and tissue engineering to yield a highly performant 3D model of the kidney tubule integrated with microfluidics and in-line monitoring with on-board electronics, using organic electronic technology. The system has been designed in a multi-well plate format, with simultaneous acquisition to allow medium-throughput screening. We demonstrate multi-parameter monitoring of relevant parameters to predict renal tubule toxicology, including TEER, and metabolite levels, under fluidic conditions. Our system is compatible with high-resolution imaging and has potential for in situ immunofluorescence staining (as shown in Fig. 1 using RFP-actin labelled MDCK Ⅱ cells pictured on the device). In addition analysis of secreted biomarkers is possible by periodic sampling of efflux from the microfluidic chambers. We have monitored both canine and human kidney proximal tubule epithelial cells, in the presence or absence of endothelial cells to more closely mimic in vivo conditions.