CHEN 4800/5800: Bioprocess Engineering
University of Colorado, Spring 1996

Homework Set #4
Due: April 9, 1996

1. Cells are growing at steady state in a chemostat of volume 1 liter, with nutrient feed inlet and outlet flow rates of 1 liter/day. The inlet feed stream contains no cells, and the concentrations (Xv and Xd) of living and dead cells in the outlet stream are found to be 2 x 106 and 1 x 106 cells/ml respectively. Calculate the rates of cell growth and cell death in the bioreactor, using the cell balance equations.

To achieve a higher concentration of living cells inside the reactor, a selective recycle device is added to the outlet line, as shown in the sketch below. The reactor outlet enters this device, which recycles most of the living cells back to the reactor and removes mostly the dead cells. With the new steady state concentration of living and dead cells inside the reactor and in the outlet stream measured at the doubled flow rate through the reactor (see the sketch below) show that the living cells are growing at a lower specific growth rate in the recycle reactor. Assume negligible cell growth, death, or accumulation in the recycle device.

2. When the cell doubling time D is increased by growing the cells at lower growth rates, only the time that cells spend in G1 phase G1 increases while the time periods spent in the other phases of cell cycle S, M, and G2 remain unchanged according to the cell cycle model of mammalian cell growth. For the two different cases of growth associated (q=µ)and non-growth associated (q=x) product formation rates, determine how the steady state content of an intracellular reporter protein is expected to change with the cell growth rate.

3. Problem 15.7 from the textbook (Shuler and Kargi), for HYBRIDOMA cells.

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Prof. Dhinakar S. Kompala / Department of Chemical Engineering
College of Engineering / University of Colorado