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Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing

Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing

Bild
Disassembled Tissue Barrier-on-chip, with lower part on the left hand side and upper part on the right hand side. Both parts feature a microfluidic channel and interdigitated electrodes made of gold and transparent ITO (zoom in view on the right bottom corner). The thin sealing layer and a porous polymer membrane of PET are placed on the upper half. During cultivation, a cell layer of e.g. endothelial cells grows on the membrane, while the cells are constantly supplied with a continuous flow of the culture medium via the channels and the integrity of the barrier is measured via a resistance measurement between the electrodes. Picture: Eugen Koch

Until now, in vitro methods and animal testing have been used to predict the effect of drugs. Novel organ-on-a-chip models offer a more accurate and ethically acceptable alternative. An important application of organ-on-chip systems is the investigation of drug transport and absorption through native cell barriers such as the blood-brain barrier. In this work, a chip platform with important innovations was developed for practical use in drug permeation testing. First, the design enables the transfer of barrier-forming tissue into the microfluidic system after the cells have been seeded on nanoporous membranes. This allows the application of highly reproducible models and cultivation protocols established for static drug testing. The system consists of a microscopic glass chip with two liquid compartments with transparent embedded interdigitated electrodes separated by the membrane. In principle, the chip can be used many times for different experiments as well as for other types of tissue barriers. The non-permanent closure allows a free choice of membrane materials. The barrier tissue can be continuously monitored by measurements with integrated transparent microelectrodes. Supplemented by automated fluid control, the chip system represents a promising platform for investigating established in vitro models of tissue barriers under reproducible microfluidic perfusion conditions. In this way, drug candidates can be evaluated in preclinical studies under well-controlled conditions and thereby reduce animal testing.

Original Article:

Koch, E. V., Ledwig, V., Bendas, S., Reichl, S. & Dietzel, A. Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing. Pharmaceutics 14; 10.3390/pharmaceutics14071451 (2022). www.mdpi.com/1999-4923/14/7/1451

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