ABSTRACT
This chapter discusses the benefits and the techniques of high cell density perfusion bioreactors for culturing mammalian cells. Perfusion refers to the continuous inflow of nutrient medium coupled with the outflow or harvesting of spent medium, while the cells are fully or partially retained within the bioreactor. In contrast to the chemostat bioreactor, in which the outflow stream contains cells at the same concentration as in the bioreactor, the outflow stream of a perfusion bioreactor is either completely or substantially depleted of cells. The concept of perfusion was applied as early as 1912 to keep small pieces of tissue alive for extended periods of observation under a microscope (1,2). A historical account on the development of perfusion bioreactors for mammalian cell cultivation is given in an earlier review (3). While many of the perfusion techniques discussed earlier pertain to attachment cultures and are still applicable, this chapter focuses more on perfusion techniques for suspension bioreactor cultures, as these homogeneous cultures have become increasingly popular in the ensuing decade (4).
