Module 4 - Design of Bioreactors
Module 4 - Design of Bioreactors
Module 4
Part 1
Substrate balance
𝑑𝑥 " !& 𝑑𝑠 " 𝜇𝑥 "
= 𝜇𝑥 " , = 𝐹 = 𝑉𝐷 = 𝐹𝑠$ − 𝑠 & = total amount
𝑑𝑡 !" 𝑑𝑡 𝑌-/( of substrate
𝑑𝑝#
= 𝑞+ 𝑥𝑚(𝑉. + 𝐹𝑡)
𝑑𝑡
Repeated fed-batch culture.
-Part of the culture volume is removed at certain
intervals
"$ " 0#
𝑝 = 𝑝. "
+ 𝑞+ 𝑥/ ( "$ + 1
)t
Example: In a fed-batch culture operating with intermittent addition of glucose
solution, values of the following parameters are given at time t = 2 h, when the system
is at quasi-steady state.
V = 1000 ml
a)Find V0 (the initial volume of the culture).
so =100 g/l
b)Determine the concentration of growth-limiting substrate in F = dV /dt= 200 ml/h
the vessel at quasi-steady state. 𝜇()* = 0.3/h
c)Determine the concentration and total amount of biomass in Ks = 0.l g/l
the vessel at t = 2 (at quasi-steady state). 𝑌*/, = 0.5g/g
d. If qP = 0.2 g product/g cells-h, po = 0, determine the
concentration of product in the vessel at t = 2 h. 𝑥-& =30 g
Solution c)
𝑥 " = 𝑥0" + 𝐹𝑌-/( 𝑠0 t
𝑎)
𝑥 " = 30 + 0.2 ∗ 0.5 ∗ 100 ∗ 2 = 50 𝑔
𝑉 = 𝑉𝑜 + 𝐹𝑡
-' 45
𝑥2 = = =50g/l
𝑉𝑜 = 𝑉 − 𝐹𝑡 &. *3" 5.7*5.8∗8
=16g/L
c)
Solution
𝑥2 = 𝑥𝑜 + 𝑌𝑥 /𝑠𝑠𝑓 = 20𝑔/𝐿 + 0.3 300 g/L=110g/2L=55 g/L
𝑎)
𝑥 " = 𝑥0" + 𝐹(𝑌-/( 𝑠𝑓)t
𝑉 = 𝑉𝑜 + 𝐹𝑡 x ; = 20 ∗ 500 + 50 ∗ 0.3 ∗ 300 ∗ 10 = 55,500g
𝑉 = 500 + 50 10 = 1000 or -' 44455
𝑥2 = = =55g/l
&. *3" 455*45∗:5
b)
d) 𝑝 = 𝑝. "$ + 𝑞+ 𝑥/ ("$ + 0#)t
" " 1
D=F/V = 50/1000=0.05/h
455 455 5.54(:5)
𝑝 = 0.1( ) + 0.05 (55)( + )10=20.675g/L
[\3 :555 :555 8
s=
]456^[ pt =p (V)= (20.675)*1000=20,675 g
_._h(_.h)
s= _.a^_._h
= 0.167g/l
Note: Problem 9.4 (Shuler and Kargi)
For repeated fed-batch culture of the same problem in 9.4 (Shuler and Kargi)
A fed-batch repeated culture is carried out using the same
condition as in the previous slide, calculate the following:
a) g
b) tw
c) pw
= 500/1000=0.5
Dw=F/Vw = 50/1000=0.05/h
2 =
pw=gpo+ 10>
" #
(1-g2)
8.8?(??)
pw=0.5(0.1)+ 1(8.8?)
(1-0.52)
=20.675g/L
Non-sterile CSTR-Single Bioreactor
BK@
0= At steady state
BD
𝐹
(𝑥b −𝑥_ ) = 𝜇𝑥b
𝑉
𝐷(𝑥b −𝑥_ ) = 𝜇𝑥b
(𝑥b −𝑥_ )
𝜇=𝐷
𝑥b
𝑑𝑥b 𝑥0
𝐹𝑥_ − 𝐹𝑥b + 𝜇b 𝑉𝑥b = 𝑉 𝜇 = 𝐷(1 − )
𝑑𝑡 𝑥1
𝑥0
𝜇1 = 𝐷1(1 − )
𝑥1
Multiple Bioreactors CSTR
For n stages
CSTR in Series
𝜇a 𝑥a = D2(𝑥a −𝑥b )
𝜇p 𝑥p = 𝐷p (𝑥p − 𝑥p^b )
𝑟K,p = 𝐷p (𝑥p − 𝑥p^b )
At stage 1 for microorganisms
𝐾( 𝜇: 1
𝑠: = 𝑥9 = 𝑥0 + 𝑌)/- (𝑠. −𝑠9 ) 𝑟K,p = (𝑥p − 𝑥p^b )
𝜇2 − 𝜇: Θp
Material balance at stage 2 for
microorganisms 1
𝑑𝑥a Θp = (𝑥p − 𝑥p^b )
𝐹𝑥b − 𝐹𝑥a + 𝜇a 𝑉a 𝑥a = 𝑉a 𝑟K,p
𝑑𝑡
𝑑𝑥a
𝑉a =0 at steady state Can be solved graphically (area
𝑑𝑡 under curve)
𝜇a 𝑥a = D2𝑥a − 𝐷2𝑥b
𝑥b
𝜇a = D2(1 − ).
𝑥a
Sample Problem – Multiple Reactors
x0 = 4 g/l
a. so=50g/L
F=500 L/h
CSTR1
p1 = 22 g/l
x1
*$ s1
𝜇= 𝐷(1 − ) D1,
*%
! !"! " $$"%
Yp/x= =0.71=
#!"#" #!"&
are µmax = 1.5 h-1 and Ks = 2g/L. The yield Yx/s is s1 = 12.65g/l
0.83 and Yp/x, is 0.71. If the outlet product
concentration is maintained at 22 g/L. 𝜇'() 𝑠1
𝜇=
a) Calculate the dilution rate, s, x and the 𝐾* + 𝑠1
volume of the tank
b) If one reactor is added, what is the cell, +.-(+$./-)
substrate, concentration in the first reactor, 𝜇= =1.295/h
$1+$./-
of same volume. What are the volumes of
the two bioreactors. Compare the volumes
obtained using one CSTR and two CSTR 5
1.295= 𝐷(1 − ), D=1.46/h
system. 34
8 466
V= = = 341.97 𝐿
9 :.5<
).+()-.5+)
b. 𝜇2 = -.)-.5+
=1.295/h
CSTR1 CSTR2
Eq.2÷Eq.1
p2 = 22 g/l 45.325 𝐷1[35 − (4 + 0.83 50 − 𝑠1 )]
x2 = 35 g/l =
1.5𝑠 𝐷1[4 + 0.83(50 − 𝑠1) − 4]
s2 = 12 .65g/l (2 + 𝑠1 )4 + 0.83(50 − 𝑠1)
1
At Reactor 1
D2=?
5 45.325 35 − (4 + 0.83 50 − 𝑠1)
𝜇1 = 𝐷1(1 − ) 1.5𝑠1
=
[4 + 0.83(50 − 𝑠1) − 4]
*%
𝜇120 𝑠1 2 + 𝑠1 [4 + 0.83(50 − 𝑠1)]
𝜇1 =
𝐾, + 𝑠1
1.5𝑠1
s1=39.15 g/L
𝜇1 = 𝑥1 = 4 + 0.83(50 − 𝑠1)
2 + 𝑠1
).+,! / 𝑥1 = 4 + 0.83(50 − 39.15)
-.,!
= 𝐷1(1 − 0 ) =13.00 g/L
#
u u
uc Z uc Z+Dz
𝑐 𝑐 + ∆𝑐
x0 x1
so s1
F F
Same equation as
in Batch
𝑉𝑑𝑐
= 𝑉𝑟NO In general
𝑑𝑡
𝑑𝑥
𝑌(𝑠0 − 𝑠) = 𝑥 − 𝑥5
= 𝜇𝑥 For microorganism 𝑥 = 𝑥5 + 𝑌(𝑠0 − 𝑠)
𝑑𝑡
𝑑𝑥 𝜇()* 𝑠 ds − µ34# s
= 𝑥 = [x + Y(s6 − s)]
𝑑𝑡 𝐾, + 𝑆 dt Y (K 5 +s) %
𝑥 − 𝑥5 Integrate with limits of
𝑌-/( =𝑌=
𝑠0 − 𝑠 t = 0, s = s0,
t = t, s = s,
𝑌(𝑠2 − 𝑠) = (𝑥 − 𝑥% )
𝑑𝑠 𝑑𝑥 𝑥% + 𝑌(𝑠2 − 𝑠) 𝑠
−𝑌 = 𝑥% + 𝑌(𝑠2 + 𝐾* )ln − 𝐾* 𝑌ln = 𝜇'() 𝑡(𝑥% + 𝑌𝑠2 )
𝑑𝑡 𝑑𝑡 𝑥% 𝑠2
𝑑𝑠 −1 𝑑𝑥
=
𝑑𝑡 𝑌 𝑑𝑡
𝑑𝑠 −1 𝜇120 𝑠
= 𝑥
𝑑𝑡 𝑌 𝐾, + 𝑠
Example
The growth rate of E. coli can be expressed by Monod kinetics with the
parameters of µmax =0.935/h and KS =0.71 g/L. Assume that the cell yield is 0.6 g dry cells
per g substrate. If xo is 1 g/L and so 10 g/L when the cells start to grow exponentially, at t =
0, show how x, s, change with time.
a) What is the cell and substrate concentration after 1, 1.5 hours?
b) At 20%, 50% and 70% substrate conversion, what is the residence time (for PFF) and
time t for batch cultivation
c) Plot conversion vs time
d) Using the plot, find the residence at 70% and 80% substrate
conversion
µmax =0.935/h Substrate
KS =0.71 g/L conversion (-) s (g/L) x (g/L) t (h)
YX/S = 0.6 dry cells per g substrate 0.0 10.0 0.00 0.00
xo = 1 g/L 0.1 9.0 0.60 0.54
so = 10 g/L 0.2 8.0 1.20 0.91
0.3 7.0 1.80 1.19
Solution 0.4 6.0 2.40 1.42
0.5 5.0 3.00 1.62
𝑥 = 𝑥5 + 𝑌(𝑠0 − 𝑠) 0.6 4.0 3.60 1.79
𝑥6 + 𝑌(𝑠- − 𝑠) 𝑠 0.7 3.0 4.20 1.95
𝜇()* 𝑡(𝑥6 + 𝑌𝑠- ) = 𝑥6 𝑌(𝑠- + 𝐾, )ln + 𝐾, 𝑌ln 0.8 2.0 4.80 2.10
𝑥6 𝑠-
0.9 1.0 5.40 2.26
𝑥6 + 𝑌(𝑠- − 𝑠) 𝑠
𝜇()* 𝑡(𝑥6 + 𝑌𝑠- ) = 𝑥6 +𝑌(𝑠- +𝐾, )ln + 𝐾, 𝑌ln
𝑥6 𝑠-
12.00
10.00
8.00
s
s or x(g/L)
6.00
4.00
2.00
x
0.00
0.00 0.50 1.00 1.50 2.00 2.50
time (h)
x (g/L) s (g/L)
+)( 5.4@4(4)
s= = =16.21 g/L
'120 ,+ 5.A,5.4B4
=5g/L
xopt=Yx/s(sf-s) =0.65(85−16.21)=44.71
' A&WX - 8.E(?)
D=" = = ?C? = 0.35/ℎ Or
BY CD xopt= 𝑌)/* ( 𝑠8 + 𝐾𝑠)(1 −
9&
)
9 & 15'
' ?88
V = 0 = 8.F?= 1428. 57𝐿 4
xopt= 0.65( 85 + 5)(1 − ) = 44.71
4LM4
The cell concentration of the outlet stream is
Since x is larger than xopt , need two reactors in series.
x =Yx/s(sf – s)= 0 .65 (85 - 5) =52 g/L
At the second stage
𝑉𝑇 = 𝑉1 + 𝑉2
= 934.58 + 200.8 = 1135.38𝐿
𝑥: (𝑉𝑇 − 𝑉)/𝑉𝑇 =
𝜇8 = D2(1 − ). =(1428.57 − 1135.38)/1428.57 x100
𝑥8 = 20%
𝜇()* 𝑠2 0.7(5)
𝜇P = )= = 0.35/ℎ
(𝐾𝑠 + 𝑠2 5 + 5)
<( %.=-
𝐷$ = ) = =2.49 /h
(+" * ) +"&-/-$
)(
𝐹 500𝑙/ℎ
𝑉2 = = = 200.8𝐿
𝐷2 2.49/ℎ
For the second stage using PFF
umax 0.7 1/h
Ks 5 g/L
sf 85 g/L
F 500 L/h
Yx/s 0.65
F
x1
s1 F
x2
s2
𝑥6 + 𝑌(𝑠- − 𝑠) 𝑠
𝑥6 + 𝑌(𝑠- + 𝐾, )ln + 𝐾, 𝑌ln = 𝜇()* 𝑡(𝑥6 + 𝑌𝑠- )
𝑥6 𝑠-
𝑥: + 𝑌(𝑠: − 𝑠2) 𝑠2
𝑥: + 𝑌(𝑠: + 𝐾, )ln + 𝐾, 𝑌ln = 𝜇()* 𝑡(𝑥: + 𝑌𝑠: )
𝑥: 𝑠:
A
𝑠) = 16 B
A
𝑠- = 5 B
x1= 45g/l
F
x1
s1
F
x2
s2
(a) (b) (c)
For a single steady-state CSTRFwith a sterile feed, the dilution xopt=Yx/s(sf-s) =0.4(50−8.204)=16.72
rate is equal to specific growth rate:
Second reactor
3 '"#$ ( 5.4(:4) 𝜇()* 𝑠2 0.5(8)
D= = = = 0.441/ℎ 𝜇P = = ) = 0.4/ℎ
& )% *D 8*:4 (𝐾𝑠 + 𝑠2) (2 + 8
<( %.&
𝐷$ = ) = =-2.059 /h
3 855 (+" * ) +"+/.>$/+&
V= = = 543.51 𝐿 )(
+ 5.@@:
Not possible!!!
The cell concentration of the outlet stream is Since, the x concentration at the second recorder
x =Yx/s(sf – s)= 0 .4 (50- 15) =14 g/L exceeds the design concentration at first reactor,
second reactor is not needed. Why will you spend
Check if x=14 g/L is than less or more money of putting a second recorder if you already
reached your target with one reactor.
than xopt
Sample Problem Bioreactor: Single or Multiple
A certain microorganism obeys the Monod equation where µmax =0.5hr-1 and Ks = 2
g/L. The cell yield Yx/s is 0.4. The flow rate and the substrate concentration of the inlet
is 600 L/hr and 50 g/L, respectively. The substrate at the exit tank is 96% converted
a) If single CSTF is used what is the size?
b) If two CSTFs (firs is optimized) are used what is the size of each?
c) If one CSTF followed by PFF (in series) are used what is the size of each?
so=50g/L
=50(1-0.96)=2g/L
a. One CSTF
s=50(1-0.96)=2g/L
x=0.4(50-2)=19.2g/L
' A&WX - 8.?(1)
D=" = BY C-
= 1C1 = 0.25/ℎ
3 855
V= = = 800 𝐿
+ 5.84
so=50g/L s2=2g/L 𝑉𝑇 = 𝑉1 + 𝑉2
x2=19.2g/L = 496.28 + 103 = 600𝐿
V, P
2-Stage 496.3 L 103L 600L
Dopt=µmax(1- V,L,N
) =0.5(1− PL46
)=0.402
9V, 6.56P(P)
s= = =8.204 g/L (𝑉 − 𝑉𝑇 )/𝑉𝑇 =
W$%& 09 6.406.56P
=(800 − 600)/800 x100
= 25% smaller if 2 CSTF are used
xopt=Yx/s(sf-s) =0.4(50−8.204)=16.72
Since x2 is larger than xopt , two reactors are needed
8 P66
V1 = 9 = 6.56P= 496.28 𝐿
!
Second reactor
𝜇()* 𝑠2 0.5(2)
𝜇P = = ) = 0.25/ℎ
(𝐾𝑠 + 𝑠2) 2+2
c) For two stage reactor (CSTF + PFF) No. of Stage V1 CSTF) V2 (PFF) VT
First reactor is at optimum
Second reactor is evaluated using outlet condition 1-Stage 800 L 0L 800L
F (𝑉 − 𝑉𝑇 )/𝑉𝑇 =
x1 =(800 − 576)/800 x100
s1 = 28% smaller: (if 2 CSTF’s are used)
F
x2 Rank (From worse to best
s2 1. CSTF+PFF (576 L)
(𝑥: + 𝑌(𝑠: + 𝐾, ))ln
*% + ^(,% 0,') ,
+ 𝐾, 𝑌ln , ' = 𝜇()* 𝑡(𝑥: + 𝑌𝑠: ) 2. CSTF+CSTF (600 L)
*% %
3. CSTF (800 L)
A
𝑠) = 8.204 B
A
𝑠- = 2 B
x1= 16.72g/l