Transport in a grooved perfusion flat-bed bioreactor for cell therapy applications

This study considers the transport of oxygen (a growth-associated solute) a nd lactate (a metabolic byproduct) in a flat-bed perfusion chamber modified to retain cells through the addition of grooves, perpendicular to the dire ction of flow, at the chamber bottom. The chamber has been successfully app lied to hematopoietic cell culture and may be useful for other basic and ap plied biomedical applications. The objective of this study is to characteri ze the culture environment in terms of solute transport under various opera tional conditions. This will allow one to improve the design and operating strategy of the perfusion system for maximizing cell numbers. The system is numerically simulated using the finite element package FIDAP. The reaction kinetics describing oxygen uptake by cells are simplified to zero order to give an upper bound for the oxygen consumption. A flat-bed chamber without grooves is considered here as a benchmark. We show that the growth environ ment is not oxygen limited (local oxygen concentration above 10 mu M) for a variety of flow rates and culture conditions (qo(2) = 0.1 mu mol/(10(6) ce lls h)). With a medium flow rate of 2.5 mL/min through the reactor, the mod el predicts that the 29-cm(2) reactor can support at least 33.4 x 10(6) tot al cells when the inlet medium is in equilibrium with high (20%) oxygen con centration. The culture becomes oxygen limited however for the same flow ra te for low (5%) oxygen concentration and can only support 7.2 x 10(6) total cells. Comparison of grooved vs nongrooved chambers reveals that the prese nce of grooves only affects solute transport on a local scale. This result is attributed to the small size (200 mu m) of the cavities relative to the chamber dimensions. The comparison also yields an empirical relation that a llows for rapid estimation of oxygen and lactate concentrations in the groo ves using only the numerical simulation of the simpler nongrooved chamber. Finally, our investigation shows that, while decreasing the spacing between cavities decreases the total number of cells the reactor can support, the efficiency of the reactor is increased by 25% (on an area basis) without gr owth restriction.