Design of well and groove microchannel bioreactors for cell culture

Abstract

Microfluidic bioreactors have been shown valuable for various cellular applications. The use of micro-wells/grooves bioreactors, in which micro-topographical features are used to protect sensitive cells from the detrimental effects of fluidic shear stress, is a promising approach to culture sensitive cells in these perfusion microsystems. However, such devices exhibit substantially different fluid dynamics and mass transport characteristics compared to conventional planar microchannel reactors. In order to properly design and optimize these systems, fluid and mass transport issues playing a key role in microscale bioreactors should be adequately addressed. The present work is a parametric study of micro-groove/micro-well microchannel bioreactors. Operation conditions and design parameters were theoretically examined via a numerical model. The complex flow pattern obtained at grooves of various depths was studied and the shear protection factor compared to planar microchannels was evaluated. 3D flow simulations were preformed in order to examine the shear protection factor in micro-wells, which were found to have similar attributes as the grooves. The oxygen mass transport problem, which is coupled to the fluid mechanics problem, was solved for various groove geometries and for several cell types, assuming a defined shear stress limitation. It is shown that by optimizing the groove depth, the groove bioreactor may be used to effectively maximize the number of cells cultured within it or to minimize the oxygen gradient existing in such devices. Moreover, for sensitive cells having a high oxygen demand (e.g., hepatocytes) or low endurance to shear (e.g., human embryonic stem cells), results show that the use of grooves is an enabling technology, since under the same physical conditions the cells cannot be cultured for long periods of time in a planar microchannel. In addition to the theoretical model findings, the culture of human foreskin fibroblasts in groove (30 microm depth) and well bioreactors (35 microm depth) was experimentally examined at various flow rates of medium perfusion and compared to cell culture in regular flat microchannels. It was shown that the wells and the grooves enable a one order of magnitude increase in the maximum perfusion rate compared to planar microchannels. Altogether, the study demonstrates that the proper design and use of microgroove/well bioreactors may be highly beneficial for cell culture assays.

Compact heat exchange reactor for synthesis of mixed alcohols

“…Many reactions have been tested in microchannel reactors such as water gas shift [22], steam reforming [25], partial oxidation [26][27][28], Fischer Tropsch synthesis [29,30], synthesis of methanol [31], methane oxidative coupling [32], photocatalysis [33], catalytic combustion [34] and as a bioreactor [35]. These are just a few examples and the applications are spreading quickly.…”

Microfluidic Platforms for Hepatocyte Cell Culture: New Technologies and Applications

“…Tilles et al demonstrated that with internal membrane oxygenation in the bioreactor, flow conditions that resulted in low wall shear stresses generated higher albumin and urea synthetic rates compared with flow conditions that resulted in high wall shear stresses. Detailed parametric study of well and groove microchannel bioreactors was presented by Korin et al 28 Operation conditions and design parameters were theoretically examined via a numerical model. The complex flow pattern obtained at grooves of various depths was studied, and the shear protection factor compared with planar microchannels was evaluated.…”

A microfluidic traps system supporting prolonged culture of human embryonic stem cells aggregates

“…The oxygen consumption rate (OCR) for the EB bulk was set according to Michaelis-Mentin kinetics with respect to oxygen concentration (Cochran et al 2006;Korin et al 2009):…”