Continuous microcarrier-based cell culture in a benchtop microfluidic bioreactor.

Microfluidic bioreactors are expected to impact cell therapy and biopharmaceutical production due to their ability to control cellular microenvironments. This work presents a novel approach for continuous cell culture in a microfluidic system. Microcarriers (i.e., microbeads) are used as growth support for anchorage-dependent mammalian cells. This approach eases the manipulation of cells within the system and enables harmless extraction of cells. Moreover, the microbioreactor uses a perfusion function based on the biocompatible integration of a porous membrane to continuously feed the cells. The perfusion rate is optimized through simulations to provide a stable biochemical environment. Thermal management is also addressed to ensure a homogeneous bioreactor temperature. Eventually, incubator-free cell cultures of Drosophila S2 and PC3 cells are achieved over the course of a week using this bioreactor. In future applications, a more efficient alternative to harvesting cells from microcarriers is also anticipated as suggested by our positive results from the microcarrier digestion experiments.

On the pinning of interfaces on micropillar edges.

Microsystems for biotechnology often make use of pillars to perform the targeted microfluidic functions. In many cases the role of the pillars is to block or maintain fixed an interface between two immiscible fluids. This phenomenon is usually called pinning. The pining principle is used for capillary valves, liquid-liquid extraction devices, etc. It is common to estimate the pinning efficiency by considering mathematically perfect edges. In reality, microfabricated edges always show some smoothness that can be modeled by a small curvature radius. In this work, we investigate the pinning on square, circular, triangular, and diamond-shaped pillars, and analyze the anchoring on the upstream edges (first pinning conditions) and possibly on the downstream edges (second pinning conditions). It is shown that pinning efficiency decreases very quickly with the curvature radius of the pillar edge. It is concluded that the quality of the microfabrication is essential. Especially oxidation of the silicon reduces considerably the pinning efficiency. Moreover, it is shown that square pillars pin better an interface than triangular pillars. For triangular pillars, a pillar angle--angle between two facets--optimal for pinning has been determined that depends on the quality of microfabrication.