Web Release Date: August 22,
Transport in a Grooved Perfusion Flat-Bed Bioreactor for Cell Therapy Applications
Accepted July 20, 1998. Abstract: This study considers the transport of oxygen (a growth-associated solute) and lactate
(a metabolic byproduct) in a flat-bed perfusion chamber modified to retain cells through
the addition of grooves, perpendicular to the direction of flow, at the chamber bottom.
The chamber has been successfully applied to hematopoietic cell culture and may be
useful for other basic and applied biomedical applications. The objective of this study
is to characterize the culture environment in terms of solute transport under various
operational 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 environment is not oxygen limited (local
oxygen concentration above 10 Download the full text:
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M) for a variety of flow rates and culture conditions
(qO2 = 0.1 mol/(106 cells h)). With a medium flow rate of 2.5 mL/min through the
reactor, the model predicts that the 29-cm2 reactor can support at least 33.4 × 106
total cells when the inlet medium is in equilibrium with high (20%) oxygen
concentration. The culture becomes oxygen limited however for the same flow rate
for low (5%) oxygen concentration and can only support 7.2 × 106 total cells. Comparison of grooved vs nongrooved chambers reveals that the presence of grooves only affects
solute transport on a local scale. This result is attributed to the small size (200 m)
of the cavities relative to the chamber dimensions. The comparison also yields an
empirical relation that allows for rapid estimation of oxygen and lactate concentrations
in the grooves 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 growth restriction.
