No abstract

Organ-on-chip (OoC) technology is one of the most promising in vitro tools to replace the traditional animal experiment-based paradigms of risk assessment. However, the use of OoC in drug discovery and toxicity studies remain still limited by the low capacity for high-throughput production and the incompatibility with standard laboratory equipment. Moreover, polydimethylsiloxanes, the material of choice for OoC, has several drawbacks, particularly the high absorption of drugs and chemicals. In this work, we report the development of a microfluidic device, using a process adapted for mass production, to culture liver cell line in dynamic conditions. The device, made of cyclic olefin copolymers, was manufactured by injection moulding and integrates Luer lock connectors compatible with standard medical and laboratory instruments. Then, the COC device was used for culturing HepG2/C3a cells. The functionality and behaviour of cultures were assessed by albumin secretion, cell proliferation, viability and actin cytoskeleton development. The cells in COC device proliferated well and remained functional for 9 days of culture. Furthermore, HepG2/C3a cells in the COC biochips showed similar behaviour to cells in PDMS biochips. The present study provides a proof-of-concept for the use of COC biochip in liver cells culture and illustrate their potential to develop OoC.

Luer slip is one of the gold standards for chip-to-world interface in microfluidics. They have outstanding mechanical and operational robustness in a broad range of applications using water and solvent-based liquids. Still, their main drawbacks are related to their size: they have relatively large dead volumes and require a significant footprint to assure a leak-free performance. Such aspects make their integration in systems with high microchannel density challenging. To date, there has been no geometrical optimization of the Luer slips to provide a solution to the mentioned drawbacks. This work aims to provide the rules toward downscaling the Luer slips. To this effect, seven variations of the Luer slip male connectors and five variations of Luer slip female connectors have been designed and manufactured focusing on the reduction of the size of connectors and minimization of the dead volumes. In all cases, female connectors have been developed to pair with the corresponding male connector. Characterization has been performed with a tailor-made test bench in which the closure force between male and female connectors has been varied between 7.9 and 55 N. For each applied closure force, the test bench allows liquid pressures to be tested between 0.5 and 2.0 bar. Finally, the analysis of a useful life determines the number of cycles that the connectors can withstand before leakage.