Introducción a los

Bioreactores

Reactor Batch
Prof. Pablo Araujo Granda Ph.D.

paaraujo@uce.edu.ec
 Lecturas iniciales

• Documentos en aula virtual

• Cap. 13. Reactor Engineering - Bioprocess

Engineering Principles - Doran 1995
he knowledge base and its
roblems or disturbances. operating strategy has a signific
conversion, product concentration,
Modos de Operación
w information about pro- - Tipos
ledge base. To maximise nation and process reliability.
elligent supervisory con- Characteristics such as final subst
• Discontinuo
and representative concentrations and the time requir
data- Batch
and engineering knowl- determined for different reactor ope
• Alimentación
n rule formulation and intermitente
balances. –
For Fed-Batch
a general reaction syst
Expert systems can also change of component masses in the
• Alimentación Continua
tion - CSTR
using Eq. (6.5):
ting unmeasurable fer-
contradictory data and
dM
lism [30-33].
nce with applications in dt
neural networks. Neural
xtracting useful informa-
 13 Reactor Engineering 353

Discontinuo – Mezcla perfecta - Batch

fed-batch and continuous reactors for enzyme conversion and
fermentation.
Figure 13.19 Flowsheet for a stirred batch enzyme-reactor.

13.5.1 Batch Operation of a Mixed Reactor

Batch processes operate in closed systems; substrate is added at J
the beginning of the process and products removed only at the

• Ni entran ni salen
end. Aerobic reactions are not batch operations in the strictest
sense; the low solubility of oxygen in aqueous media means
that it must be supplied continuously while carbon dioxide

líquidos
and other off-gases are removed. However, reactors with
neither input nor output of liquid are classified as batch. If
there are no leaks or evaporation from the vessel, the liquid
volume in batch reactors can be considered constant.
Most commercial bioreactors are mixed vessels operated in

• No fugas
batch. The classic mixed reactor is the stirred tank; however
mixed reactors can also be of bubble column, airlift or other
configuration as long as concentrations of substrate, product
and catalyst inside the vessel are uniform. The cost of running

• No evaporación
a batch reactor depends on the time taken to achieve the
desired product concentration or level ofsubstrate conversion;
operating costs are reduced if the reaction is completed quick-
ly. It is therefore useful to be able to predict the time required

• Volumen = cte
for batch reactions.

13.5.1.1 Enzyme reaction

Let us apply Eq. (6.5) to the limiting substrate in a batch
enzyme reactor such as that shown in Figure 13.19./f/i = /Qo
- 0 because there is no substrate flow into or out of the vessel;
 (11.31). Therefore, the mass and integr
(13.7)
- f dt = f m+S ds
13 Reactor Engineering Vmax sand K m is
where Vmax is the maximum rate of enzyme reaction
Reacciones enzimáticas - Batch
the Michaelis constant. Because V is constant in batch reac-
tb -
355
tors, we can take it outside of the differential and cancel
Enzima
through the“normal” to give:and integrating with initial condition s - so at t
(13.7)
equation
As discussed in Section 11.5, enzymes are subject to deactiva- where t b i
-- e-katdt
of tion.
1.5, enzymea s are
enzymes
Thus, them concentration
reaction
subject Vmax
toand 5K m is
deactiva-
tion of active enzyme inthe reactor,
of
--
active
t b -
e-katdt
K m
enzyme
= f Km+S
inthe
In n
s o reactor,
ds. +
s o - sf
strate con
Vand
is constant
therefore
dt inthe
batch
Km+s valuereac-
of Vmax, may change during reaction. produce a
f Vmax, may change during reaction. Vmax ZYmax0SSf Vmax
the
When differential
deactivation and iscancel
significant, variation of Vma x with time (13.12)
nificant, variation of Vmax with time (13.8) from Eq.
can be
(11.44) expressed
so that using
Eq. (13.8) Eq. (11.44)
becomes: so that
Integrating Eq. (13.8)
Eq. (13.12) becomes:
with initial conditionIntegrating
s = sn at t = 0E
Enzima Desactivada gives:
where t b is the batch reaction time gives:
required to
ds D
--VmaxOe-kdtS
tb -
1 [
strate concentration
In 1 - kd
So s0sf)]
fromInson to +sf. _The
_ _
batch t
1
dt Km+s(13.11) produce
k d a certain concentration
Pmax0 sf of Vmax0
product
tb - can
(13.8) (13.11)
from Eq. (13.10) and stoichiometric relationsh
(13.13)
kd
of Vmax before deactivation occurs
eactivation rate constant. Separating where t b is the batch reaction time and sf is the final substrate
where Vmax0 is the value of concentration.
Vmax before deactivation occurs
Inhibición enzimática
 - lzxV - kdxV.
dt Ifxfis the final biomass concentration after batch culture ti d
. Because/~ in batch culture remains of
%, rearrangement approximately
Eq. (13.17)constantgives: and (13.15) (13.17) tu
Cultivo celular - Batch
equal to/%ax for most of the growth period
Because/~
if k clfinal
in batch culture remains
likewise remains constant,
(see
Figure Section
13.20
approximately 11.7.3),
Flowsheet for a stirred batch fermenter.
constant and ge
Ifxfis the biomass 1 we can integrate
concentration xf afterEq (13.16)culture time
batch
equal
For to/%ax
directly to findfor
Vconstant, most
t bEq.
the of thebetween
= (13.15)
relationship growth
becomes: . period
In ~batch time and(seecell
r Section 11.7.3)co
%, rearrangement
if concentration.
k cl likewiseUsing of Eq.
remains ~ (13.17)
m a x
the initial- kd gives: Xo
condition that
constant, we x=can x 0 atintegrate
t= 0:
J
Eq (13.16)
(13.1
d x to find the
directly relationship between batch time and cel
x = xoe(/~max- kd)t.
1- ( / ~ - k d ) x. xf
t b concentration.
= dt Using
If the rate the
In initial
~of. cell deathcondition that
is negligible x= x 0 atwith
compared
(13.17) t= 0:
grow
~ m a x - k d <</Um~Xo
kd and Eqs (13.17) and (13.18) reduce(13.16)
to:
Ifxfis the final biomass concentration after batch culture time
x = xoe(/~max- kd)t.
%, rearrangementXof"-Eq. (13.17) (13.18)
Xoe ~maxt gives:
(13.17)
(13.1
1 xf
If the ratet bof
= cell deathIn ~ is. negligible compared with growth,
Ifxfis the~ mfinal - kd
a xand: Xo concentration after batch culture time
biomass
k d <</Um~ and Eqs (13.17) and (13.18) reduce(13.18) to:
%, rearrangement of Eq. (13.17) gives:
If the rate of cell death is lnegligiblexfcompared with growth,
X "- Xoe ~maxt tb - In - - .
k d <</Um~ and Eqs (13.17) and (13.18) reduce to:
1 ~max xf X0
t bX "-= Xoe ~maxt In ~ . (13.19)
(13.2
 -- - - ++ ++m
ms sxV.x.(13.23)to pVwhere p
ume. Assuming
dt d t YxsYxs Yvs
YPS
Cultivo Celular – Producto no asociado
Because x is a function of time, we must substitute an expres-
to(13.22)
rp Vwhere r
(13.2
According to E
sion for x into Eq. (13.23) before it can be integrated.
al metabolismo energético - Batch
For/r equal to/~max and Vconstant, we can write
Assuming cell death is negligible, x is given by Eq. (13.19).
where
Eq. qv is the
(13.22)
Because
as:
Therefore: x is a function of time, we must substitute an expr

S('maxqqp)t )
R G = rv V=T
sion for x into Eq. (13.23) before it can be integrat
ds
Assuming- - cell death is+ negligible, x is given by Eq. (13.1p
dt ~ + YPS~+ m Xo e+m~.
m s x.
and, from Eq.A(
Therefore:
dt Yxs YPS

S('maxq )t
to
(13.24) (13.23)
dCpv u
- q
to
If all the bracketed
Because x is aterms are constant
function of time, during
we mustculture, Eq. an expres-
substitute dt
(13.24)dtcan be integrated A
sion for x into ~ directly+withYPS~
Eq. (13.23) initial
+ condition
m it Xo
before canes -m~.
so
be integrated.
at t - 0 to obtain the following equation: w
Assuming cell death is negligible, x is given by Eq. (13.19).(13.2
If cell death is
Therefore:

S('maxq )t
1 s o - - sf for Vconstant,
t b -- In l + ( )
If all~ mtheax bracketed1 terms qp are constantms during culture,
@
+ + x0
(13.24)dt can be integrated directly
~ YXS + ~max
YPS~+ m with
YPS Xo initial condition
e m~.
~max
dt
qpsan
x- -

at t - 0 to obtain the following equation: (13.24)

 Cultivo Celular – Producto asociado
357

al metabolismo energético - Batch

true biomass 1 s o - - sf
roduct
ue forma-
biomass t b 1 -- In 1+
s o - - sf
andforma-
uct m s is the t b -- In 1+ (. 1 ms)
d m sthe
is the (. 1 m s )+ xo
6.5) mass- + rxs t'm.
xo
) the mass- rxs t'm. (13
(13.26)
Despreciando
If, in el mantenimiento
addition, maintenance requirements can be neglecte
If, in addition, maintenance requirements can be neglected:

(13.22)
(13.22)
t b -- t b -- In 1 +In 1 +(so - se) (so. - se) .
/~max /~max X0 X0
e Eq.
Eq. (13.22)
(13.22) (13.27) (13
 for Vconstant, we can write Eq. (13.29) as:
)
x0 @If cell death is
~Umanegligible
X t x is given by Eq. (
Cultivo celular- –qp
Concentración
x 0 de producto - Batch
for
dt Vconstant, we can write Eq. (13.29) as:
e .

)
(
s (13.25)
x0 @ ~UmaXt
x
substrate
If qp is constant,
- qp x
Eq. 0(13.30)
e can
. be integrated directl
dt
initial condition p - P0 at t= 0 to obtain the following
tion for batch culture time as a function of the final p
at (13.25)
all to qP = constante
concentration pf:
lysis (see
canbe
substrate
s directly tinitial
b-
1 [
condition
In 1 + p - P0 at ( P ft=
]
If qp is constant, Eq. (13.30) can be integ
- P o0
) to
" obtain t
xpression tion ~max
for batch cultureXOqPtime as a function o
at all to
separate (
concentration pf:
 Ejercicio enzima - Batch
I3 Reactor Engineering 354
,

Example 13.1 Time course for batch enzyme conversion

An enzyme is used to produce a compound used in manufacture ofsunscreen lotion. Vmax for the enzyme is 2.5 mmol m -3 s- 1;
K m is 8.9 mM. The initial concentration of substrate is 12 mM. Plot the time required for batch reaction as a function of sub-
strate conversion.

Solution:
so = 12 mM. Converting units of Vma~ to m M h - 1:
3600 s 1 m3
Vm~ = 2.5 mmol m - 3 s- l .
lh 10001
= 9 mmol1-1 h - I
= 9mMh -l.
Results from application ofEq. (13.10) are tabulated below and plotted in Figure 13E 1.1.

Substrate conversion sf tb
(%) (mM) (h)
I3 Reactor Engineering 358
i i

Ejemplo cultivo celular - Batch

density can beevaluated using Eq. (13.18) or (13.2b). If cell of maintenance metabolism. For negligible cell death and con-
death is negligible, the time required for a particular level ofs'ub- stant qv, the batch time required to achieve a particular product
strate conversion can be calculated using Eq. (13.25), (13.26) or concentration can be found from Eq. (13.31). Application of
(13.27) depending on the type of product and thi: importance these equations is illustrated in Example 13.3.

Example 13.3 Batch culture time

Zymomonas mobilis is used to convert glucose to ethanol in a batch fermenter under anaerobic conditions. The yield ofbiomass
from substrate is 0.06 g g- 1; YPXis 7.7 g g- 1. The maintenance coefficient is 2.2 g g- 1 h - 1; the specific rate of product forma-
tion due to maintenance is 1.1 h - ]. The maximum specific growth rate of Z. mobilisis approximately 0.3 h - 1.5 g bacteria are
inoculated into 50 litres of medium containing 12 g l- 1 glucose. Determine batch culture times required to:
(a) produce 10 g biomass;
(b) achieve 90% substrate conversion; and
(c) produce 100 g ethanol.

Solution:
Yxs = 0.06 g g - l ; ypx= 7. 7 gg-l;/Umax = 0. 3 h-l; ms=2.2 gg-1 h-l; mp= 1.1 h -1 9x0=5g/501=O.1 g l - ] ; s 0 = 12 g1-1.
(a) If 10 g biomass are produced by reaction, the final amount ofbiomass present is (10 + 5) g = 15 g. Therefore xf= 15 g/50 1
= 0.3 g 1- ]. From Eq. (13.20):

1 0.3g1-1
tb = In = 3.7h.
0.3 h -1 0.1 g1-1
 tpt~. t l ~ -------- t b thv ,~ tplb.-Itl~ tb-s thv

Tiempo total
tT reactor
-" Batch
tT "-
I
tion
Time occurs. These time perio
I
xf tion processes in I Figure 13.21
= I
r
tdn associated with batch react

8 tdn=thv+tp+tl
tion occurs.
Xo "11These timeI periods --V" are illustratedi for fermenta
tion processes in Figure
tpt~. t l ~ -------- tb thv ,~ tplb.-Itl
13.21. ~
Therefore, tb-s the thv
total downtim
tdn associated with -"and operation
tT batch reactor the total
tT batch
is: "- reaction tim
Time

tdn=thv+tp+tl tT=tb+tdn.
(13.32
Algunos problemitas

• Del capítulo 13 de Dorán

• Realizar los ejercicios: 13.1, 13.2 y 13.3