Reactor Engineering

Bioreactor
O A device within which biochemical
transformations are caused by the action
of enzymes or living cells
O Frequently called a fermenter whether
the transformation is carried out by living
cells or in vivo cellular components (that
is, enzymes).
 Key aspects of
bioreactor design
O Reactor configuration
O Stirred tank? Or air-driven?
O Reactor size
O Mode of operation
O Batch
O Continuous
O Processing conditions
O T, pH, DO tension
O Controls
O Optimization
Bioreactor configuration

Glacial Lakes Energy in Watertown, South Dakota

47+ million gallon per year ethanol production
 Bioreactor Configurations
O Classification based on operation modes
O BATCH (stirred-tank)
O CONTINUOUS
O Chemostat
O Fluidized bed
O MODIFIED
O Chemostat with recycle
O Fed-batch
O Multistage continuous reactors
 Bioreactor Configurations
O Classification based on oxygen supply
O AEROBIC
O airlift
O ANAEROBIC

O Classification based on form of biocatalyst

O FREE CELL / ENZYME
O IMMOBILIZED ENZYME/CELL
O PACKED-BED REACTOR
O MEMBRANE REACTOR
 Bioreactor Configurations

Airlift reactor configurations: (a) and (b) internal

loop vessels; (c) external loop airlift.
Typical stirred tank fermenter for
aerobic culture
 Ideal reactor design
O Final biomass, substrate and product concentrations
and time required for conversion can be determined
using mass balances.

For a general reaction system:

dM
= M in - M out + RG - Rc
dt
Rate of mass Rate of
accumulation Rate of Rate of Rate of consumption
mass in mass out generation
 Batch operation
in a mixed reactor
O Substrate is added at the
beginning of the process
and products removed only
at the end.

V
S
p
Uniform concentration
of substrate, catalysts
and product
 Batch operation
in a mixed reactor

0 0 0

dM
= M in - M out + RG - Rc
dt
V
S
where P
S – substrate concentration
V – liquid volume
P – product concentration
 Batch operation
in a mixed reactor
Since

M = SV and RC = vV

d(SV ) vmax S dS vmax S

=- V =-
dt Km + S dt Km + S

where M – mass of substrate

V – volume of liquid
S – substrate concentration
 Batch operation
in a mixed reactor
Km + S
dt = - dS
vmax S
Integrating at t = 0; S = S0
t = t; S = S

K m S0 1
tb = ln + ( S0 - S )
vmax S vmax
 Batch operation
in a mixed reactor
When the enzyme is deactivated: 𝑣𝑚𝑎𝑥 = 𝑘2 𝐸𝑎 = 𝑘2 𝐸𝑎0 𝑒 −𝑘𝑑 𝑡

-kd t
dS vmax 0 e S
=- where vmax0 – vmax before
dt Km + S deactivation

1 é æ Km S0 1 öù
tb = - ln ê1- kd ç ln + ( S0 - S ) ÷ú
kd ë è vmax 0 S vmax 0 øû
 Batch operation
in a mixed reactor

When the enzyme is immobilized:

dS vmax S
= -hT
dt Km + S

ηT – total effectiveness factor

 Batch operation
in a mixed reactor
Sample problem 1
An enzyme is used to produce a compound used in
the manufacture of sunscreen lotions. vmax for the
enzyme is 2.5 mmol m−3 s−1; Km is 8.9 mM. The initial
concentration of substrate is 12 mM. Plot the time
required for batch reaction as a function of substrate
conversion.
Suppose the enzyme deactivates with half-life 4.4
h. What is the batch reaction time required to achieve
90% substrate conversion.
 Batch operation Benefit gained from
conversions above 80 to

in a mixed reactor 90% must be weighed

against the significantly
greater reaction time,
and operating costs,
Solution: involved.
6

5
Batch reaction time (h)

0
0 20 40 60 80 100
Substrate conversion (%)
 Continuous operation
in a mixed reactor
Feed stream Product stream
O Also referred to as
continuous stirred tank F F
reactor (CSTR) or Si S
continuous stirred tank Pi P
fermenter (CSTF).

V
S
P
 Continuous operation
in a mixed reactor
Feed stream Product stream

F F
Si S
Pi P If the vessel is well mixed,
the product stream has the
same composition as the
liquid in the reactor.
V When used with freely
S suspended cells or enzymes,
P the catalyst is continuously
withdrawn from the vessel in the
product stream.
 Steady-state operating strategies
O Chemostat
O The liquid volume is kept constant by setting the inlet and outlet flow rates
equal.
O The dilution rate (D = F/V) is constant and steady state is achieved as
concentrations in the chemostat adjust themselves to the feed rate.

O Turbidostat
O The liquid volume is kept constant by setting the outlet flow rate equal to the
inlet flow rate; however, the inlet flow rate is adjusted to keep the biomass
concentration constant.
O The dilution rate adjusts to the steady-state value required to achieve the
desired biomass concentration.
CSTR operating parameters
O Dilution rate (D) and residence time (τ)

1 V • The amount of material that can

t= = be processed over a given period
of time is represented by the flow
D F rate F.
• For a given throughput, the
reactor size V and associated
where capital and operating costs are
minimised when  is made as
V – reactor size (m3)
small as possible.
F – flow rate (m3/s)
 CSTR: Enzyme reaction
O For a limiting substrate in a CSTR at steady-state:

Feed stream Product stream

F F
Si S
Pi
0 0
P

dM
= FSi - FS + RG - Rc
dt
V vmax S
S FSi - FS = V
P
Km + S
 CSTR: Enzyme reaction
O For a limiting substrate in a CSTR at steady-state (with
free enzymes continuously replaced, vmax = constant ):

vmax S
D(Si - S) =
Km + S

O For immobilized enzymes:

hT vmax S
D(Si - S) =
Km + S
 Sample problem 2
Mushroom tyrosinase is immobilized in spherical beads
of diameter 2 mm for conversion of tyrosine to dihydroxy-
phenylalanine (DOPA) in a continuous, well-mixed reactor.
The Michaelis constant for the immobilized enzyme is 2
gmol m-3. A solution containing 15 gmol m-3 tyrosine is
fed into the reactor; the desired level of substrate
conversion is 99%. The reactor is loaded with beads; all
enzyme is retained within the vessel. The intrinsic vmax for
the immobilized enzyme is 1.5 x 10-2 gmol s-1 per m3
catalyst. The effective diffusivity of tyrosine in the beads
is 7 x 10-10 m2 s-1. External mass transfer effects are
negligible. Immobilization stabilizes the enzyme so that
deactivation is minimal over the operating period.
Determine the reactor volume needed to treat 18 m3 of
tyrosine solution per day.
 Effectiveness factor for
internal diffusion
Generalized Thiele modulus: 1st-order kinetics rA = k1CA
VP k1
f1 =
Sx DAe

Sphere R k1
f1 =
3 DAe

Flat plate k1
f1 = b
DAe
 Effectiveness factor for
internal diffusion
1st-order kinetics: rA = k1CA
Sphere 1
2 (
hi1 = 3f1 coth3f1 -1)
3f1

e x + e- x
coth x = x - x
e -e

Flat plate tanh f1 e x - e- x

hi1 = tanh x = x - x
f1 e +e
For ϕ1 > 10 1
hi1 »
f1
 Continuous operation
in a plug flow reactor
F
Sf
O Alternative to CSTR
O No mixing occurs (ideal PFR)
F O Liquid entering passes through as a
S z+Dz discrete plug and does not interact
L Δz with neighboring fluid elements
O achieved at high flow rates
SZ
O Occurs most readily in column or
F z tubular reactors
O Liquid flows at constant velocity (all
parts of the liquid have identical
F residence time in the reactor)
Si
 Continuous operation
in a PFR: Enzyme reaction
O Mass balance equation for substrate for a section, Δz

dM
= M in - M out + RG - Rc
dt
n max S
F S z - F S z+Dz - ADz = 0
Km + S
dS n max S
u =- where u – superficial
dz Km + S velocity through the
column
 Continuous operation
in a PFR: Enzyme reaction
O Integrating from
S = Si at z = 0
S = Sf at z = L

éK S S - S ù
L = uê m ln i + i f
ú
êën max S f n max úû
 Continuous operation
in a PFR: Enzyme reaction
O Residence time:
V L
t= =
F u

Km Si Si - S f
t= ln +
n max S f n max
 Continuous operation
in a PFR: Enzyme reaction
O For immobilized enzymes

dS n max S
u = -hT
dz Km + S
 Sample problem 3
Immobilized lactase is used to hydrolyze lactose in
dairy waste to glucose and galactose. The enzyme is
immobilized in resin particles and packed into a 0.5-
m3 column. The total effectiveness factor for the
system is close to unity. Km for the immobilized
enzyme is 1.32 kg/m3 and vmax is 45 kg/m3-h. The
lactose concentration in the feed is 9.5 kg/m3. A
substrate conversion of 95% is required. The column
is operated under plug flow conditions. At what flow
rate should the reactor be operated.