MImETIC INDiRECT · MIcrovascularizED Tumour-on-chip for Cellular ImagiNg of Drug Response and Cell moTility

MIcrovascularizED Tumour-on-chip for Cellular ImagiNg of Drug Response and Cell moTility

MImETIC INDiRECT aimed to create a versatile microfluidic (MF)/organ-on-chip (OoC) toolkit for cost-effective, standardized methodologies creating advanced in vitro models (AIM) to study cell motility and drug response. Envisioned toolkit versatility fostered cross-platform compatibility under perfusion or static AIM approaches exploiting commercially available 24-multiwell (24MW) consumables. The OoC field currently lacks well-defined or established regulatory guidelines, where commercial entities each provide an unique, non-standardized products for end-users in academia and industry. Regulatory uncertainty and reluctance of adoption is echoed in the OoC markets, with conservatively low predicted compound annual growth rates (CAGRs). Adoption of OoC technologies require significant financial and investment where a plethora of patents, publications and commercial products instils confusion in end-users. Comparative advantages of OoC to “golden standard” technologies do not always demonstrate cot-incentive advantages for robust scientific application. These sentiments were echoed in a 2017/18 European Research Commission Joint Research Panel report. A 40-60% cost-saving and higher success turnover is predicted with OoC adoption in the drug development pipeline, currently requiring 13-15 years and ±USD2.6 billion per compound. However, end-users recognize OoC advantages for improved physiological recapitulation in vitro, once standardization and cost-barriers are addressed. Objectives were informed by initiating a technology- and market-landscape, with step-wise toolkit development: (i) design, fabrication and technical validation of consumables and biomaterial blends; and (ii) biological validation with proof-of-concept using commercially available cell lines to establish a microvascularized in vitro liver model. The Cherry CubiX platform was used to demonstrate proof-of-principle by providing multiparametric control of liquid perfusion to mimic blood flow; temperature regulation; and dissolved gasses (O2, CO2) management. In conclusion, it was successfully demonstrated that a standardized, robust toolkit and methodology can be established on a multiparametric platform (Cherry CubiX) to study AIMS liver pathology. However, fostering technology adoption remains a challenge in a small market embroiled in regulatory uncertainty, with early adopters currently the target end-users.

Data: CORDIS, © European Union