Biomedical Engineering Reference
In-Depth Information
18.13. You wish to produce active retrovirus, and you are investigating the effect of
temperature on the process. Active virus is subject to decay with a rate constant,
k
d
¼
2.2 day
1
at 37
C and 0.76/day at 31
C. The rate of virus production from
a packaging cell line is k
p
¼
3.5 virus
$
cell
1
$
day
1
at 37
C and 3.0
10
6
cells and the volume of the
liquid medium is 5 mL. The initial number of virus in solution is zero. How many
viruses are there in 1 mL solution 1 day after initiation of virus production if the
temperature is maintained at 35
C?
18.14. What value of k
L
a must be achieved to sustain a population of 5
virus
$
cell
1
$
day
1
at 31
C. Assume that there are 5
10
9
cells/L when the
10
12
mol-O
2
/(h cell)?
18.15. Hybridoma cells immobilized on surfaces of Sephadex beads are used in a packed
column for production of monoclonoal antibodies (Mab). Hybridoma concentration
(X) is approximately 5 g/L in the bed (total bed volume). The flow rate of the
synthetic medium and glucose concentration are: Q
oxygen consumption is 0.1
40 g/L,
respectively. The specific rate constant for glucose consumption is 1 L/(g-X
$
day).
Assume that there are no diffusion limitations and glucose is the rate-limiting
nutrient. Determine
(a) the volume and the packed bed height for 95% glucose conversion. Bed diameter
is D
R
¼
¼
2 L/h and S
0
¼
0.2 m. Neglect the growth of the hybridomas and assume first-order
kinetics.
(b) the effluent Mab concentration and overall productivity if YF
P/S
¼
4 mg-Mab/g-S.
18.16. A small laboratory reactor is used to obtain data on the growth of E. coli on glucose.
The vessel is cylindrical with a liquid volume of 1 L and is 0.1 m in diameter. The walls
and the base of the vessel are covered with a film of E. coli, which grows to
a concentration of 10
5
cells/m
2
. The reactor is operated as a chemostat, with an inlet
substrate concentration of 2.0 g/L glucose. The yield coefficient for E. coli may be
taken to be 10
7
cells/g-glucose, and the maximum specific growth rate is 0.8 h
1
. The
Monod constant K
S
is 100 mg glucose/L.
The vessel is to be used to collect data on the kinetics of E. coli growth under glucose
limitation. How would the observed yield coefficient vary with dilution rate under
these conditions of wall growth? Plot X/(S
0
S) a function of D. What fraction of the
substrate is consumed by cells attached to the wall? In determining the kinetics
parameters, only the bulk cell and substrate concentrations are measured, and the
contribution by cells attached to the wall is ignored. The cells on the wall consume
substrate at a rate described by the Monod equation with the kinetic constants given
above. Their number remains constant due to the combined effects of cell growth and
cell lysis.
If a washout experiment is performed (D is set at a value greater than the maximum
growth rate and the cell concentration in the exit stream is monitored with time) what
is the behavior you would expect in the presence and absence of wall growth? Plot the
cell concentration as a function of time for both cases.