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Fall 2018 Homework #7 Due November 20th by the end of class to the TAs 1. Chemostat with Recycle and Cell Concentration Glucose
vest SX SXh
SXr You are running a 1000L chemostat with recycle, but your cells keep dying. Upon
investigation, you discover that the effluent media is highly acidic, so you add a second
feed for the continuous delivery of sodium bicarbonate, which maintains the reactor at an
optimal pH and solves your problem. Bicarbonate acts as a buffer and is not involved in
the reaction. Both feeds are sterile, the glucose feed concentration is 2.0 g/L with flow
rate 100 L/hr, and the bicarbonate feed concentration is 3.5 g/L with flow rate 50 L/hr.
The recycler has a volume recycle ratio of 0.2 and a cell concentration factor of 2.0. The
yield coefficient YX/S is 0.5 g cells/g S and the growth is described by kinetic parameters
Ks = 100 mg/L and µm = 0.3 hr -1.
Assume kd = 0. The recycler does not concentrate glucose or bicarbonate.
a) In the boxes above, write the expressions for the flow rate of the Effluent,
Recycle, and Harvest streams. b) At steady state, derive an expression for the specific rate of cell growth, µg.
Calculate the dilution rate and µg and compare them.
c) Derive an expression for the steady state concentration of cells in the reactor.
Calculate for qp = 0. 2. Immobilized Cell Bioreactor
The liver bioreactor shown below is a fluidized-bed reactor, where primary liver
cells from pigs have been seeded onto spherical plastic particles. The cells form a
Catapano and Gerlach
Bioreactors for Liver Tissue Engineering
biomatrix (biofilm) of average thickness L = 0.15mm.
When fat-soluble toxins in the
patient’s blood encounter the cells in the bioreactor, they are converted into watersoluble toxins that are removed
downstream by a membrane
separation process with 100%
efficiency. The patient’s blood is
being pumped through the
bioreactor at a flow rate of
300ml/hr and the concentration
of toxins in this feed stream is
0.025mg/ml. The conversion of
the toxins follows MichaelisMenten kinetics with the
assumption of first order
reaction kinetics (e.g. relatively
Fig. 3. Clinical
low substrate concentration).
Vmax = 0.50mg toxins/mmBAL
hr and Ks = 0.25mg
utilizing the bioreactor developed
by Gerlach et al.  loaded with 600 g of primary porcine cells.
toxins/mm . The specific surface area of the biofilm in the reactor is 1.25 mm2/mm3.
The diameter of the column is 100mm and the height is 500mm.
In 1997, Flendrig et al. proposed another packed-bed bioreactor with decentralized oxygen
of high allowable
density liver cells
with low nutrientsof
toxins in the blood leaving the
what does the
gradients . Primary
of a spiral
3D polyester non-woven
packed in a cylindrical
directly need to be?
perfused with medium or plasma flowing along the bioreactor length (Figure 2d). Microporous b.) Calculate
oxygen Assume all fat-soluble
toxin at a 1:1 (wt/wt) ratio
supply and CO 2 removal.
fabric in in vivo-like
aggregates, to synthesize urea and proteins, and to transform lidocaine into MEGX and xilidine
for up to 2 weeks. Use of the bioreactor for the EC treatment of animal models of ALF caused
a significant enhancement of the survival rate of small and large laboratory animals  and
was proven safe in the treatment of ALF patients . Recently, Ambrosino et al. proposed to 3. Fed-batch Culture couple the polyester fabric with a porcine autologous biomatrix to enhance cell attachment to
the 3D scaffold
later on Morsiani
et al. to
concept by arranging the fabric in an annular packed-bed bioreactor and by flowing medium or
plasma radially across the fabric to enhance oxygen transport to the cells and reduce the
bioreactor inlet/outlet pressure drop (Figure 2e).
Up to ca. 230 g primary hepatocytes could be cultured in such bioreactor in a high
metabolically active state . BALs based on this bioreactor are under clinical testing. an antibiotic. a.) Name two advantages of using a fed-batch process over CSTR production.
b.) Using mass balances on cells and substrate, i.e. starting from and
where X and S stand for the total amount of biomass in the reactor and the total
amount of substrate in the reactor
respectively, derive the following function: X t X 0t FYXM/ s S0t ...
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- Summer '19
- Immobilized Cell Bioreactor