Parallelized microfluidic biochips in multi well plate applied to liver tissue engineering

In this paper, we present a tool box to perform parallelized microfluidic cultures. The box was made in polycarbonate (PC) using a 24-well plate format. The microfluidic biochips were made in polydimethylsiloxane (PDMS). Two wells of the PC plate were used as inlet/outlet and fluid reservoir for one biochip. A hermetic cover was fabricated in PC to allow continuous and sterile dynamic cell cultures. Thus, the entire set up, called IDCCM for “Integrated Dynamic Cell Cultures in Microsystems” allowed the perfusion culture of 12 biochips simultaneously. To demonstrate the potential of the IDCCM box and the cell functionality, we analyzed the behaviour of HepG2/C3a liver cells. For that purpose, we have investigated the effects of the inoculated cell density and of the flow rates on the cell proliferation, glucose consumption, albumin production and the cytochrome P450-1A activity over 96 h of cultures. The results have shown that the cell proliferation and the cytochrome P450-1A activity were cell density and flow rate dependent. This led to identify a best optimized condition with HepG2/C3a at (5–7) × 105 cells/biochip (corresponding to (2.5–3.5) × 105 cells/cm2) and at a perfusion flow rate of 25 μL/min. This result highlighted the functionality of the HepG2/C3a cells in parallelized microfluidic culture conditions and illustrated the potential for larger in vitro toxicity studies using the IDCCM tools.