1. Terry A. Ring Chemical Engineering University of Utah
Batch Bio Reactor Design Ch 6 & 10 Bioprocess Engineering-Basic Concepts
Terry A. Ring
Chemical Engineering
University of Utah

2. Bio Processing Examples
See g/community/studen ts/student-design- competition/past- problems
Competition
Teams of 4 students
Start to form Teams
Individual

3. Overview of Biopharmaceutical Plant
10 pg/cell/day
1 mL = 106 cells
1,000 kg/yr

4. Cell Growth Cycle ~100x Days
For this process the doubling time is 36 hrs after lag time

5. Seed Train Demands For Each Cell entering the process
~2.7x108 cells must be generated to go into the production reactor
More than 4 seed reactors generating 100x cell multiplication
Seed Train
1st reactor is 100 mL
2nd reactor is 10 L
3rd reactor is 1000 L
Production reactor

6. Seed Train Demands For Each Cell entering the process
~2.7x10^14 cells must be generated to go into the production reactor
Seed reactors generating 100x cell multiplication in each
One reactor is ~7 doubling times
~7*36 hr=10.5 days in each reactor

7. Cell Kinetics Nutrient utilization
Net specific grow rate = growth – death
X can be cell mass or cell number

8. Cell Kinetics and Doubling Time

9. Cell Death Rate
Combining Forms
μnet = μg-kd

10. Cell Growth Cycle
Days

11. Utilization of Substrate (glucose) and Product Production
Growth-associated Product Generation
dS/dt=dX/dt * (YX/S)-1
dP/dt=dX/dt*(YX/S)-1*YP/S= YP/Sμg
dO2/dt=μgX/YX/O2 = kLa(C*-CL) or

12. Growth Kinetics
Substrate limited growth

13. Product Inhibited Growth
P = Product Concentration, Kp= is product binding constant

14. Inhibition by Toxic Compound
Inhibitor binds with KI binding constant

15. Combining Substrate and Cell Growth Kinetics
Solve for X vs time (t)

16. Reactors Aspects of CSTR Aspects of Fed Batch Control pH Dissolved O2
Liquid Level
Reactor Volume

17. CHEMOSTAT Material Balance on the cell concentration, X
Dilution rate, D=F/VR =1/τ, τ = residence time
At steady state when little death
In – out + cell growth – cell death = accumulation
Optimal Dilution Rate for max. P and X

18. Cell Growth Cycle
Days

19. Production Reactor
2.7x108 cells must be generated to go into the production reactor
10 pg/cell/day
Gives 1,000 kg/yr at 24/7 365 days/yr
What is the total size of the production reactors
Max cell density w/o death = 109cells/mL
VR=274 L minimum (no down time all year)
But you can be more accurate than this!!
VR=

20. Combining Substrate and Cell Growth Kinetics
Solve for X vs time (t)

21. CHEMOSTAT Material Balance on the cell concentration, X
Dilution rate, D=F/VR =1/τ, τ = residence time
At steady state when little death
In – out + cell growth – cell death = accumulation
Optimal Dilution Rate for max. P and X