Chemostat

Hadiyanto
Fed-batch exercise
Fed Batch Reactor
Reactor Design Equation
V dN A
FA0 FA rA dV
dt
No outflow FA = 0
Good Mixing rA dV term
out of the integral

dN A d C A V
FA0 rA V
dt dt
 Fed-batch cont.
Cell balance sterile feed
rfi mX
KS D
S
dX
( m D) X mm D
dt
This can be a steady state reactor if substrate is
consumed as fast as it enters (quasi-steady-state).
Then dX/dt = 0 and m = D, like in a chemostat.
Recall, D = F / V
 Fed batch cont
Substrate balance no outflow (Fcout = 0), sterile feed
St = SV and Xt = XV (mass of substrate or cells in reactor at a given
time)
S0 = substrate in feed stream
substrate
in substrate
consumed
Substrate no substrate out
dS t
mX t
balance D ( S0 S ) (Flow out = 0)
dt YX / S
Cell dX t
balance mXt
dt
 Fed batch cont.
Quasi steady state for St change in substrate
is very small in reactor and is consumed as
rapidly as fed

mXt
DS0
YX / S
t
dX
m X t FYX / S S0 Integrating from t=0 to t
dt
X t X 0t FYX / S S0t
Chemostat
 Fed batch cont.

X X FYX / SS0 t
t t
0

What this means

the total amount of cells in the reactor
increases with time
dilution rate and m decrease with time in fed
batch culture
Since m = D, the growth rate is controlled by
the dilution rate.
 Solution
dV
Fin
dt
Fin Fin Vt t
dV Fin dt
Vo 0

Vo Vt

Vt=Vo+Fin .t Vo=16 m3
solution
 Continuous Reactors

Chemostat - CSTR - continuous stirred tank reactor for the cultivation of cells.
mixing supplied by impellers and rising gas bubbles
assume complete mixing - composition of any phases do not vary with position
liquid effluent has the same composition as the reactor contents
 Mass Balance on Chemostat
Acc = in - out + gen - cons
dci
VR Fcif Fci VR rfi
dt
VR - reactor volume
F - volumetric flow rate of feed and effluent streams (they are
equal)
ci - concentration of component i in the reactor
cif - concentration of component i in the influent or feed stream
 If we have a steady state reactor - no changes in
composition with time F
then dci and r (c c )
0 fi i if
dt VR
F 1
D
Define as the dilution rate - VR
reciprocal of the mean holding or residence time
detention time
For cell mass, if we assume a sterile feed:
ci = X and Xf = 0 and
rx = mX then mX = DX
D=m at SS
 Chemostat with Monod Kinetics
mmS S
KS
mD
KS S mmm 1
The above equations only holds if mmmax >1
If mmmax < 1 or D>m
washout of the cells occurs
Cells leave the reactor faster than they are dividing.
mmS f
Dmax Near washout the reactor is very sensitive to variations in D

KS S f Small change in D large shifts in X and/or S

If mmax = 0.5 hr-1 then D< 0.4 hr-1
 Intracellular Product Formation -
Chemostat
dci
VR Fcif Fci VR rfi
dt
Steady State and ci = P

DPf P YP / X mX 0
If Pf = 0

YP / X mX
P
D
 Substrate Balance on Chemostat -
Intracellular Product
dci
VR Fcif Fci VR rfi
dt
If ci = S
1 dS
FS0 FS VR mX VR
YX / S dt

At Steady State
mX
DS 0 S X YX / S S0 S
YX / S
With Monod
Ks D
X YX / S S0
mm D
 Chemostat with Extracellular
Product
Cell Mass Balance
dX
VR FX 0 FX VR mX
dt
Dm
Substrate Balance
1 1 dS
FS0 FS VR mX VR qP X VR
YX / S YX / P dt

Solve Substrate at SS for X

 Class Exercise

E. coli is cultivated in continuous culture under

aerobic conditions with glucose limitation. When
the system is operated at D= 0.2 hr-1, determine the
effluent glucose and biomass concentrations
assuming Monod kinetics (S0 = 5 g/l, mm= 0.25 hr-1 ,
KS = 100 mg/L, Y x/s = 0.4 g/g)
 Chemostat with Recycle
FR, XR

F, X0 F, X2

V, X1

F+FR, X1

F - nutrient flow rate

V - reactor volume
X1 - x concentration in reactor
X2 - X concentration in effluent
XR - X concentration in recycle
FR - recycle flow rate
 Chemostat with Recycle Cell mass
equation
Acc = in - out + gen
dX 1
F X0 + FR XR - (F+ FR) X1 + VmX1 =V
dt

FR, XR

F, X0 F, X2
V, X1

F+FR, X1
 Chemostat with Recycle cont.
Define Substitutions
a = FR/F F + FR = (1 + a)F
recycle ratio FRXR term
C = XR /X1 FR = Fa
concentration factor XR = CX1
FRXR = aCFX1

dX 1
F X0 + FR XR - (F+ FR) X1 + VmX1 = V
dt
dX 1
F X0 + aCFX1- (1 + a)F X1 + VmX1 = V
dt
 Recycle cont
Assume
steady state dX 1 = 0 Chemostat can be
dt operated at higher
sterile feed X0 = 0 dilution rates than the
Then specific growth rate
(aC - 1 -a)F + Vm = 0 when cell recycle is
If D = F/V for recycle used.
m = D(1+ a(1 -C))

if C > 1 (concentration of cells) then a(1 - C) < 0

then m < D
 Substrate balance - Recycle
mX 1 dS
FS0 aFS V (1 a ) FS V
YX / S dt
At Steady state and substituting for m

D YX / S ( S0 S )
X 1 YX / S ( S0 S )
m (1 a aC )
 Recycle Substrate cont.
Assuming Monod

K S D(1 a aC )
S
m max D(1 a aC )
YX / S K S D(1 a aC )
X1 S0
(1 a aC ) m max D(1 a aC )
 In Class Exercise -

Consider a 1000 L CSTR in which biomass is being

produced with glucose as the substrate. The
microbial system follows a Monod relations with
mm = 0.4 hr 1, KS = 1.5 g/L, and yield factor = 0.5
g/g. If S0 = 10g/L glucose and F = 100 L/h:
What is the specific biomass production rate (g/l-h) at
SS?
If recycle is used with a recycle stream of 10 L/h and a
recycle biomass concentration five times as large as
that in the reactor exit, what would be the new specific
biomass production rate?
 Chemostat in Series

F, S0
V1, X1, S 1 F, S0
F, S1, X1

V2, X2, S 2

F2 , S 2 , X 2
 Chemostat in Series
(no additional feed)

First stage (assuming Monod)

K S1 D1
S1
m m1 D1
X 1 YX / S S 0 S1
Second Stage

dX 2
FX 1 FX 2 V2 m 2 X 2 V2
dt
 Chemostat in Series cont.
At Steady State

X1
m 2 D2 1
X2
X1
1, m 2 D2
X2
Substrate Balance

1 dS
FS1 FS 2 V2 m 2 X 2 V2
YX / S dt
 Chemostat in series

At Steady State
m2 X 2
S 2 S1
D2 YX / S

D2 = F/V2 and could have Monod growth for m2

Solve S and m equations simultaneously for

X2 and S2 once the value of m2 is known
 Chemostat in Series
(Additional Feed in Second Stage)

Cell balance around second stage

dX 2
F1 X 1 F ' X '( F ' F1 ) X 2 V2 m 2 X 2 V2
dt
At Steady State with X = 0

F1 X 1
m 2 D '2 Growth rate does not typically
V2 X 2 follow Monod in Second Stage if
F1 F ' additional feed.
D '2
V2
 Chemostat in Series cont.
Substrate Balance if Additional Feed

1 dS
F1S1 F ' S ( F1 F ' ) S 2 V2 m 2 X 2
'
0 V2
YX / S dt
At steady state the two equations can be solved
simultaneously for S2 and V2
Major advantage is to separate production
from growth
 Quiz
In a two stage chemostat system, the volumes of the first and
second reactors are 500 L and 300 L respectively. The first
reactor is used for biomass production and the second is for a
secondary metabolite formation. The feed flow rate to the first
reactor is F = 100 L/h, and the glucose concentration is 5.0 g/L.
Use the following constants for the cells.
mm = 0.3 h-1, Ks = 0.1 g/L Y X/S= 0.4 g/g
Determine the cell and glucose concentrations after the first
stage.
Assume that growth is negligible in the second stage and the
specific rate of product formation is qP = 0.02 gP/g cell hr, and Y
P/S = 0.6 gP/gS. Determine the product and substrate
concentrations in the effluent of the second reactor.
 Class Exercise 9.4
Penicillin is produced in a fed-batch culture with the
intermittent addition of glucose solution to the culture
medium. The initial culture volume at quasi-steady state is
V0= 500 L, and the glucose containing nutrient solution is
added with a flow rate of F = 50 L/h. X0 = 20 g/L, S0 = 300
g/L, mm = 0.2 h-1, Ks = 0.5 g/L and Y x/s= 0.3 g/g
Determine culture volume at t = 10 h
Determine concentration of glucose at t = 10 h
Determine the concentration and total amount of cells at t =
10 h
If qp = 0.05 g product.g cells h and P0 = 0.1 g/L, determine
the product concentration at t = 10 h
Production rate
Quiz
Comparison