simulation of a bioreactor tiffany tarrant todd giorgio
TRANSCRIPT
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SIMULATION OF A BIOREACTOR
Tiffany TarrantTodd Giorgio
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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
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BME 281: Biotechnology
• Course goal: to integrate cellular and molecular biology with process bioengineering to describe the manufacture of products derived from mammalian cells
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Why Simulate?
• based on initial lab results
• quicker, more efficient, and less expensive
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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
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Typical Cell Culture
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• 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
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Past Work
• Modeled simple exponential growth based only on cell-specific growth constant
• Accounted for oxygen delivery limitation
• Introduced different impeller types
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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
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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
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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
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Impeller Types
Rushton turbine Rushton turbine PaddlePaddle Marine PropellerMarine Propeller
Anchor Anchor Helical ribbon Helical ribbon
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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
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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
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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
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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
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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
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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
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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)
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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 (+)
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Future Work
• 1. Slight alterations to the program to make it more user-friendly
• 2. Specific documentation of program procedure and functions