SIMULATION OF A BIOREACTOR Tiffany Tarrant Todd Giorgio
Jan 18, 2016
SIMULATION OF A BIOREACTOR
Tiffany TarrantTodd Giorgio
What is a Bioreactor?
• Experimental device used to culture cells
• Provides nutrient media, oxygen support, fluid environment, area to grow
• Used both in laboratories and in industry-- specifically used in the lab portion of the BME 281: Biotechnology class
BME 281: Biotechnology
• Course goal: to integrate cellular and molecular biology with process bioengineering to describe the manufacture of products derived from mammalian cells
Why Simulate?
• based on initial lab results
• quicker, more efficient, and less expensive
Experimental Time Comparison
• Laboratory• 22 days to prepare
cells for bioreactor• 5 days to obtain a significant amount of
growth
• TOTAL: 27 days
• Simulation• approximately 1
minute to enter experimental
data and get results
• TOTAL: 1 minute
Typical Cell Culture
• HeLa--common in research labs• ECV304--endothelial cells• 293--used in BME 282 lab
• can be distinguished based on specific growth constants & the extent to which they are affected by local environmental limitations
Cell Types
Past Work
• Modeled simple exponential growth based only on cell-specific growth constant
• Accounted for oxygen delivery limitation
• Introduced different impeller types
Simple Exponential Growth
• unlimited growth
• cell types distinguished based on k
Cell Growth
0
2000
4000
6000
8000
10000
12000
0 50 100 150 200 250 300
time (hours)
cell
conc
entra
tion
(cells
/ml)
HeLa
ECV304
293
Oxygen Limitation Effects
Cell Growth
0
10
20
30
40
50
60
70
0 100 200 300 400
time (hours)
con
cen
trat
ion
(c
ells
*10^
5/m
l)
HeLa
ECV304
293
Impeller
• different types influencing the amount of power that is delivered to the bioreactor system
• increases oxygen dispersal throughout the system, thereby increasing delivery
• forces imposed on cells due to stirring causes mechanical damage and cell death
Impeller Types
Rushton turbine Rushton turbine PaddlePaddle Marine PropellerMarine Propeller
Anchor Anchor Helical ribbon Helical ribbon
Current Work
• Incorporation of impeller effects on growth
• Integration of ISF to balance oxygen delivery capabilities with cell death due to mechanical damage
• Validation of model with actual lab results
• Literature search to investigate other cell culture models
Impeller Effects
Impeller Effects
0
200000
400000
600000
800000
1000000
1200000
1400000
0 100 200 300 400
time (hours)
cell
co
nce
ntr
atio
n
(cel
ls/m
l) Rushton Turbine
Paddle
Marine Propeller
Integrated Shear Factor
Growth vs. ISF
-20
0
20
40
60
80
100
120
0 10 20 30 40
ISF
relat
ive g
rowt
h (%
)
growth
• Cell growth under different shear conditions can be correlated to an ISF factor
Stirring Speed Effects via ISF
• ISF related to speed
of impeller and its distance from the walls of the
bioreactor
Stirring Speed Effects
-50000
0
50000
100000
150000
200000
250000
300000
0 24 48 72 96 120 144 168 192
time (hours)
cell c
once
ntrati
on
(cells
/ml)
100 rpm
250 rpm
300 rpm
350 rpm
400 rpm
600 rpm
Experimental Comparisons
• Given a time lag, model correlates with BME 282 data
Model Data: Lab 293 Cells
0
200000
400000
600000
800000
1000000
1200000
0 24 48 72 96 120 144 168 192
time (hours)
cell c
once
ntrat
ion (c
ells/m
l) Model
Lab Data
Other Models
• No other model attempted to integrate several interrelated factors that affect cell growth
• Instead, focused on one parameter or determining event
• None incorporated oxygen delivery limitations
Program Flowchart
V O L U M E(in p u t ra d iu s & f lu id h e ig h t)
C A L C _ IN IT(in p u t in it ia l co n c .)
P W R N U M _ F U N C(in p u t im p e lle r typ e)
D A M A G E(in p u t im p e lle r sp e e d)
ca lcu la te s IS F
IM P E L L E Rca lcu la tes p ow e r & kLa
O X Y G E Nd e term ine s O 2 s ta te
M A IN(in p u t ce ll typ e)
Parameter Effects on GrowthCell Type Rate of exponential
growth (+)Bioreactor Radius Culture volume (+)
oxygen delivery (-)Impeller Diameter(+)
Impeller Diameter Power delivered tocells (+) & k(-)
ISF-how many cellssurvive damage (-)
Fluid Height Culture volume (+) Oxygen delivery (-)& k (-)
Concentration @each time point
When oxygenbecomes limiting(+/-)
Impeller type Power delivered tocells (+)
Deliverycapabilities (+)
Impeller Speed ISF & powerdelivered to cells(+/-)
Oxygen deliverycapabilities (+)
Future Work
• 1. Slight alterations to the program to make it more user-friendly
• 2. Specific documentation of program procedure and functions