A theoretical and experimental evaluation of a novel radial-flow hollow fiber reactor for mammalian cell culture

Abstract

A hollow fiber perfusion reactor constructed from pairs of concentric fibers forming a thin annular space is analyzed theoretically in terms of mass transfer resistances, and is shown experimentally to support the growth of an anchorage-dependent cell line in high-density culture. Hollow fiber perfusion reactors described in the literature typically employ a perfusion pathlength much greater than the distance that could be supported by diffusion alone, and analyses of these reactors typically incorporate the assumption of uniform perfusion throughout the cell mass despite many reported observations of inhomogeneous cell growth in perfusion reactors. The mathematical model developed for the annular reactor predicts that the metabolism of oxygen, carbon substrates, and proteins by anchorage-dependent cells can be supported by the reactor even in the absence of perfusion. The implications of nonuniform cell growth in perfusion reactors in general is discussed in terms of nutrient distribution. In the second part of the paper, the growth and metabolism of the mouse adrenal tumor line Y-1 in flask culture and in the annular reactor are compared. The reactor is shown to be a promising means for culturing anchorage-dependent cells at high density.