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Aerobic Bioreactor Scale-Up: Modeling and Economics: Conference Paper
Aerobic Bioreactor Scale-Up: Modeling and Economics: Conference Paper
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David Humbird
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• If advanced microbial biofuels are to measurably displace fossil fuels in the near term, they
will have to operate at levels of efficiency, margin, and scale unprecedented in the current
biotech industry.
– The challenge of attaining fuel-class production scales comes down to cost-effective delivery of oxygen
• We will explore economies of scale in oxygen delivery for aerobic bioprocessing through
– Reactor cost estimates in Aspen Capital Cost Estimator (ACCE)
– Power-optimized process simulations in Aspen Plus
– Monte Carlo sensitivity analyses using Aspen Plus integrated with Oracle Crystal Ball
2 x 5 gal
2 x 106 gal
200,000 X
• Scale-up tactics
– Hydrodynamic similarity (constant Re)
Bench – Constant agitation P/V
– Constant impeller tip speed
– Constant O2 mass transfer rate
to 20 L to 20,000 L to 200,000 L
Product
• Scale-up for constant mass transfer coefficient kLa
Oxygen uptake rate = Oxygen transfer rate
Cooling Tower Chilled Water System
OUR = OTR = kLa (C* - CL)
aeration, agitation, kLa = f (aeration, agitation)
forced-circulation cooling,
chiller loop
6 © 2015 Aspen Technology, Inc. All rights reserved.
Modeling the operating cost of oxygen delivery
Volume and OTR dependency
• Aspen Plus used to simulate single bioreactors of Agitator power dissipated as heat
kWh/kg O2
• Any beneficial economies of scale
200 m3
realized at larger vessel sizes are more 1.0
0.5
1000 m3
0.0
0 50 100 150
OUR mmol O2/L-h
4.0
3.5
Cost ratio
3.0
2.5
Vendor bare vessel
2.0 y = x0.3
1.5
1.0
3 3 3 1 2 3 4 5
1,000 m 500 m 200 m Volume ratio
4.0
ACCE bare vessel
3.5 y = x0.8
Cost ratio
3.0
2.5
Vendor bare vessel
2.0 y = x0.3
1.5
1.0
3 3 3 1 2 3 4 5
1,000 m 500 m 200 m Volume ratio
$4.0MM
1000 m3
$3.5MM
$2.0MM 200 m3
$1.5MM
$1.0MM
$0.5MM
$0.0MM
0 500 1000 1500 2000 2500
1,000 m3 500 m3 200 m3 Agitator Power (hp)
$/kg O2
$0.40 200 m3
• Significant advantage scaling from 200 to 500 m3 50 mmol/L-h
$0.30 $0.29/kg O2
• Smaller advantage scaling from 500 to 1,000 m3
$0.20
• Likely no incentive to make a bioreactor larger
than 1,000 m3 $0.10
• Minimum total power to deliver a kg of O2 • How sensitive are our conclusions to our
is fairly independent of vessel size reactor design assumptions?
• Vendor capital quotes for hypothetically • kLa [s-1] = A (us [m/s])α (P/V [W/m3])β
large reactors scale too low; ACCE – A mostly determined by units in brackets
estimates are more believable – Exponents vary with equipment and biology
– Standard size costs match remarkably well – Review paper* gives ranges for exponents
– ACCE scales more rationally 0.2 ≤ α ≤ 0.7
– ACCE provides a critical check of the 0.4 ≤ β ≤ 1.0
external quotes
• Let’s perform a sensitivity analysis
• Capital economy of scale for aerated
STRs appears to diminish above 1,000 m3
*Garcia-Ochoa and Gomez, Biotechnol. Adv. 27:153 (2009)
• In the conceptual design phase, Aspen Plus optimization routines can be used effectively
to determine minimum power demand and minimum operating cost of oxygen delivery.
• The optimized, minimum cost of oxygen delivery appears fairly insensitive to the specific
design equation (kLa correlation) used.
• For conceptual scale-up to hypothetically large equipment, cost estimates from ACCE are
as good as or better than vendor quotes when the vendor is outside of their comfort zone.