Published 10 June 2015
Updated 18 December 2015

High pressure in the pharmaceutical industry to decrease development time and costs has led to significant advancements to improve pre-clinical drug assessment. The “Body on a Chip”(BoC) develops interconnected 3D microtissues in a format compatible with existing assays to improve the relevance and speed of pre-clinical drug safety assessment.

This is a guest blog post written by Jens Kelm, CSO of InSphero, coordinator of BoC project

Back in March 2012, the BoC consortium was awarded with 1.4 mio Euro by the European Commission for the Body on a Chip project. The fact we were on the right track was confirmed not much later by the US grant initiative from the NIH and DARPA allocating more than 100 mio US$ to foster developments towards a Body on a Chip. The BoC consortium directive was to create a comprehensive, next-generation in vitro drug testing device which interconnects multi-organ tissue models to identify toxicity and/or decreased efficacy due to metabolic activity.  We started to envisage, already form the early stages, how a final market-ready product should look like. To this end, we brought an industry partner, AstraZeneca, on board to ensure our vision was consistent with the market’s needs.  One of our key learnings from this internal and external reviewing process was that not only biological significance, but also properties such as reproducibility, robustness and costs would be equally important to our clients. Therefore, the core challenge of the project became how the microfluidic design, which connects the microtissues and provides “flow” of growth medium similar to that of the human  circulatory system, could enable robust, reproducible and cost effective assays while at the same time reflecting the desired biological complexity.

These critical discussions guided us towards a very user-friendly, highly customizable Body on a Chip platform, one which simplified the process of interconnecting large numbers of more organ-like, physiologically robust 3D microtissues, rather than simply using microfluidic technologies to create individual tissue-specific models. The resulting technology and proof of concept experiments have been recently described in peer-reviewed publications in Nature Communications, the Journal of Laboratory Automation, and the Journal of Biotechnology.  The system is currently validated by the beneficiary AstraZeneca within the framework of the FETopen project, interconnecting liver and tumor microtissues to assess activation and anti-tumor effect of the chemotherapeutic drug Cyclophosphamide.

For us, a small enterprise with a little more than 30 employees, coordinating this FET Open high-tech SME project was a huge challenge, but it allowed us not only to work on next generation products, but also to examine a critical review of market needs. The interactions within the consortium, at scientific conferences and with clients generated new ideas and applications beyond the BoC system. Microtissue models such as the microliver and microheart developed in the framework of this project are used within the pharmaceutical industry but also within other EU projects such as the HECATOS. New collaborations for specific applications have emerged, and first requests for the micro-physiological system are already in place. In addition, the BoC project was recognized on the socio-ethical side in 2015, as Dr. Olivier Frey from the ETHZ in Basel was honoured by the NC3R, the National Centre for the Replacement, Refinement and Reduction of Animals in Research.

Making drug development more efficient is an important task to reduce cost on the pharmaceutical and health care system. Advanced cell culture technologies will be an integral part in the optimization process. Funding should be invested not only to understand how to make drugs safer, but also how to decrease the failure rate of lead compounds. In this sense the FETopen funding scheme enabled us to develop a micro-physiological system which has already started to penetrate into the pharmaceutical industry.

Get in touch with us via @InSphero!

Learn more about BoC project and achievements in this story!

References

Frey O, Misun PM, Fluri DA, Hengstler JG, Hierlemann A. Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun. 2014 Jun 30;5:4250.

Kim JY, Fluri DA, Kelm JM, Hierlemann A, Frey O. 96-well format-based microfluidic platform for parallel interconnection of multiple multicellular spheroids. J Lab Autom. 2015 Jun;20(3):274-82.

Kim JY, Fluri DA, Marchan R, Boonen K, Mohanty S, Singh P, Hammad S, Landuyt B, Hengstler JG, Kelm JM, Hierlemann A, Frey O. 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis. J Biotechnol. 2015 Jul 10;205:24-35.