BIOREACTOR:

DESIGN AND
OPERATION

Bioreactor- main part of any bioprocess

Main function- provide controlled environment for growth of
microorganisms/cells to obtain desired product.
 BASIC DESIGN
Considerations while designing a reactor-
1. The vessel- capable of aseptic operation continuously for days.
2. Adequate aeration and agitation - meet metabolic requirements
of micro-organisms.
3. Minimum power consumption.
4. System for temperature and pH control.
5. Appropriate sampling facilities.
6. Minimum evaporation losses.
7. Minimum use of labor in operation, harvesting, cleaning and
maintenance.
8. Internal smooth surfaces
9. Use of cheapest materials which enable satisfactory results
should be used.
 Hazard Assessment Systems
• Appropriate containment
requirements defined by
the hazard group of
organism.
• Hazard group 1- Good
Industrial Large Scale
Practice (GILSP), operated
aseptically but no
containment necessary.
• Hazard group 4- stringent
requirements of level 3.
 • Materials of
Vessel
Construction

• Agitator (Impeller)
Aeration
DESIGN OF A • Baffles
&
BIOREACOR Agitation • Aeration system
(Sparger)

• Temperature
Control • Dissolved oxygen
and • pH
Monitoring • Pressure
• Foam
Various components of an ideal fermenter for batch process are:
 I. VESSEL: Materials for body
construction of a fermenter
Traditional design is open cylindrical or rectangular vessels
made from wood or stone.
In fermentations with strict aseptic requirements it is
important to select materials that can withstand repeated
steam sterilization cycles.
It should be constructed from non-toxic, corrosion-resistant
materials.
Small fermentation vessels of a few liters capacity are
constructed from glass and/or stainless steel.
Glass is useful because it gives smooth surfaces, is non-
toxic, corrosion proof and it is usually easy to examine the
interior of the vessel.
 BASIC TYPES OF
FERMENTERS

Glass vessel with

Glass cylinder with
round/flat bottom
top and bottom
and top flanged
plates
carrying plate
Mild steel- used for penicillin production
Mild steel coated with glass or phenolic epoxy
materials used for acetone-butanol production.
 Stainless steel vessels (Steel containing > 4%
chromium) - limits corrosion
The minimum amount of chromium needed to resist
corrosion will depend on the corroding agent in a
particular environment, such as acids, alkalis, gases,
soil, salt or fresh water.
Other materials enhancing corrosion resistance-
nickel, molybdenum, tungsten, silicone and other
elements.
Steel + 18% Chromium + 10% Nickel+2-2.5 %
Molybdenum
REASON FOR CORROSION RESISTANCE IN STAINLESS
STEEL

 Depends on the existence of a thin hydrous oxide film on the

surface of the metal.
 The composition of this film varies with different steel alloys.
 The film is stabilized by chromium and is considered to be
continuous, non-porous, insoluble and self healing.
 Increasing the chromium content enhances resistance to
corrosion, but only grades of steel containing at least 10 to 13%
chromium develop an effective film.
 If damaged, the film will repair itself when exposed to air or an
oxidizing agent.
 Types of Seals
Aseptic seal made between
glass and glass, glass and metal
or metal and metal joints
between bioreactor vessel and
a detachable top or base plate.

a) Gasket seal (Glass-Glass) b) Lip seal (glass-metal) c) O-ring seal (metal-metal)

Nitryl or butyl rubbers are normally used for these seals as they
will withstand fermentation process conditions.
Double seals- difficult to assemble and to detect failure.
 II. TEMPERATURE CONTROL
Adequate provision for temperature control effect design of the vessel
Temperature control
HEAT PRODUCTION- microbial activity and mechanical agitation.

Heat requirement depends on- type of micro-organism, energy supplied

by stirring/agitation, temperature of water used for cooling.
If this heat is not ideal for particular manufacturing process then it may be
added to or removed from the system.

Provision of heat – by placing the fermenter in thermostatically controlled

bath or by use of internal heating coils or by a silicone heating jacket
through which water is circulated
Silicone jacket consists of double silicone rubber mats wrapped around
the vessel with heating wires between the two mats.

Cooling surface/cooling water. With increase in size of fermenter, silicone

jackets are inadequate to remove heat produced by fermentation process
so internal coils are used and cold water is circulated to achieve correct
temperature.
 Overall energy balance for a
fermenter
Qmet+ Qag + Q gas = Qacc+ Qexch + Qevap + Qsen

Qmet = heat generation due to microbial metabolism

Qag = heat generation due to mechanical agitation
Q gas = heat generation due to aeration power input
Qacc = heat accumulation rate by the system
Qexch = heat transfer rate to the surroundings
Qevap = heat loss rate by evaporation
Qsen = rate of enthalpy gain
 III. AERATION AND AGITATION
Purpose of aeration- provide microorganisms in submerged
culture with sufficient oxygen for metabolic requirements.
Purpose of agitation- to ensure that a uniform suspension of
microbial cells is achieved in a homogenous nutrient medium.
Aeration-agitation system comprises of-
1. Sparger- aeration system
2. Baffles
3. Agitator (Impeller)
4. Stirrer glands and bearings

Agitation not required in systems when aeration provides

sufficient agitation (air-lift fermenter) but requirements for the
same are-
1. Low viscosity medium
2. Low total solid contents
3. Vessel aspect ratio (5:1)
 A. THE AERATION SYSTEM
(SPARGERS)
Sparger- a device that is
used for introducing air
into the liquid in a

SPARGER
fermenter. Porous sparger
- It provides appropriate
oxygen for growth of Orifice sparger
micro-organisms.
- Helps in mixing reactor Nozzle sparger
contents thus reducing
power consumption.
1. Porous Sparger

Material used- sintered glass, ceramics or metal in non-agitated

vessels.
Bubble size produced - 10 to 100 times larger than the pore size
of the aerator block.
Disadvantages- Fine holes become blocked by growth of
microbial culture.
2. Nozzle Sparger

Single open or partially closed pipe to provide a stream of air

bubbles
Ideally the pipe should be positioned
centrally below the impeller
as far away as possible from the impeller
Advantage- causes a lower pressure loss + does not get
blocked.
3. Orifice Sparger
Perforated pipes
Sparger holes should be at least 6 mm (1/4 inch)
diameter because of the tendency of smaller
holes to block and to minimize the pressure
drop.
Arranged below the impeller in the form of
crosses or rings (ring sparger), approximately
three-quarters of the impeller diameter.
In most designs the air holes were drilled on the
under surfaces of the tubes making up the ring
or cross.
Mostly used with agitation in small stirred
fermenters
Orifice spargers might be used is reactors
without agitation (manufacturing of aker s
yeast, single cell protein)
Function- prevent vortex and improve aeration efficiency.

The agitation effect is only slightly increased with wider

baffles, but drops sharply with narrower baffles.

A gap between the wall and the baffle facilitates scouring

action, preventing growth of micro-organisms at these places.

Extra cooling coils may be attached to baffles to improve the

cooling capacity of a fermenter without unduly affecting the
geometry.
 B. BAFFLES
• Metal strips that
prevent vortex
formation around
the walls of the
reactor.
• Roughly one-tenth
of the vessel
diameter and
attached radially to
the wall.
• Number of baffles-
generally four
DISC TURBINE VANED DISC
 C. AGITATOR (IMPELLERS)
Agitation of suspended cell fermentations is performed in order
to mix the three phases within a fermenter
1. liquid phase contains dissolved nutrients and metabolites
2. gaseous phase is predominantly oxygen and carbon dioxide
3. solid phase is made up of the cells and any solid substrates
that may be present.
Mixing should produce homogeneous conditions and promote
a) Nutrient transfer
b) Gas transfer
c) Heat transfer
Heat transfer is necessary during both sterilization and for
temperature maintenance during operation.
Agitators may be classified as a) disc turbines, b) vaned discs, c) open
turbines of variable pitch and d) marine propellers.

Consists of a disc with a series of Vaned disc has a series of rectangular vanes
rectangular vanes set in a vertical plane attached vertically to the underside.
around the circumference.
Air from the sparger hits the underside of the disc and is displaced towards the vanes
where the air bubbles are broken up into smaller bubbles.

Vanes of variable pitch and marine propeller are attached directly to the agitator shaft
Modern Agitator Developments

- Radial flow agitator

- For a given power, high
air flow rate before
flooding
- does not give good top
to bottom blending in
a large fermenter.

Scaba 6SRGT Prochem Maxflo T

- Four, five or six hydrofoil

blades set at a critical on
a central hollow hub.
- Improved bulk mixing,
higher oxygen transfer
Lightning A315 efficiency in high viscosity
broths
 D. Stirrer Glands and Bearings
• Entry point of stirrer shaft- Top or bottom of bioreactor.
• Sealing of stirrer shaft entry point needed to operate the reactor aseptically
for long periods.
A porous bronze bearing for a 13-
mm shaft was fitted in the centre of
the fermenter top and another in a
yoke directly above it.
The bearings were pressed into
steel housings, which screwed into
position in the yoke and the
fermenter top.
The lower bearing and housing
were covered with a skirt-like shield
having a 6.5 mm overhang which
rotated with the shaft and
prevented air-borne contaminants
from settling on the bearing and
working their way through it into
the fermenter.
 Types of seals

Stuffing box
Magnetic drive
(packed gland Mechanical seal Simple bush seal
seal
seal)
A. The Stuffing Box (Packed
Gland Seal)

• The shaft is sealed by

several layers of packing
rings of asbestos or cotton
yarn, pressed against the
shaft by a gland follower.
• Two stuffing boxes on the
agitator shaft with a space
in between filled with steam
have also been used.
• These seals are sufficient for
the requirements of GILSP
containment.
B. The Mechanical Seal

• The seal is composed of two

parts, one part is stationary in
the bearing housing, the other
rotates on the shaft, and the two
components are pressed
together by springs.
• The two meeting surfaces have
to be precision machined, the
moving surface normally consists
of a carbon-faced unit while the
stationary unit is of stainless
steel.
 C. Magnetic Drive
• The impeller shaft does not
pierce the vessel.
• Two magnets: one driving and
one driven.
• The driving magnet - is held in
bearings in a housing on the
outside of the head plate and
connected to a drive shaft.
• The internal driven magnet is
placed on one end of the
impeller shaft and held in
bearings in a suitable housing
on the inner surface of the
head plate.
 Determination of KLa
(volumetric mass transfer
coefficient)
 OXYGEN SUPPLY

Dissolved oxygen is an important substrate in aerobic

fermentations.
Oxygen is sparingly soluble in water- the growth-limiting
substrate.
For bacteria and yeast cultures, the critical oxygen
concentration is about 10% to 50% of the saturated DO
(dissolved oxygen concentration).
Oxygen is normally supplied to microbial cultures in the form of
air.
The method for provision of a culture with a supply of air varies
with the scale of the process:

i. Laboratory-scale cultures may be aerated by means of the

shake-flask technique where the culture is grown in a
conical flask shaken on a platform contained in a controlled
environment chamber.
ii. Pilot and industrial-scale fermentations are normally
carried out in stirred, aerated vessels, termed fermenters.
Transfer of oxygen from air to cell during
fermentation occurrs in a number of steps:
i. The transfer of oxygen from an air bubble into
solution.
ii. The transfer of the dissolved oxygen through the
fermentation medium to the microbial cell.
iii. The uptake of the dissolved oxygen by the cell.
The rate of oxygen transfer from air bubble to the liquid phase
may be described by the equation:

Where
CL : is the concentration of dissolved oxygen in the
fermentation broth(mmoles dm3 )
t : is time (hours)
dCL/dt : the change in oxygen concentration over a time
period, i.e. the oxygen-transfer rate (mmoles O2 dm-3 h-1 )
KL : the mass transfer coefficient (cm h-1)
a : the gas/liquid interface area per liquid volume (cm2 cm-3)
C* is the saturated dissolved oxygen concentration (mmoles
dm-3 )
Terms affecting rate
• KL a
• Two quantities multiplied together
• Liquid side (essentially overall mass transfer coefficient)
• Total area of bubbles in bioreactor
• Ca t be separated

• C* (saturation oxygen concentration; max solubility of

the gas in liquid)
- Constant at a given T and P

• CL the oxygen concentration at a given time during

the run;
what we measure (C*- CL) = drivi g for e
It is extremely difficult to measure both KL and 'a' in a
fermentation and, therefore, the two terms are generally
combined in the term KLa, the volumetric mass-transfer
coefficient.

Units for KLa: h-1

Larger the value of KLa, the higher the aeration capacity of

the system.

Value of KL depends on-

1. aeration rate
2. agitation rate
3. impeller design
 Determination of KLa
Determination of KLa in a fermenter is important to establish its
aeration efficiency and quantify effects of operating variables on
oxygen supply.

Dissolved oxygen concentration monitored using dissolved oxygen

electrode

Electrode records dissolved oxygen activity or dissolved oxygen

tension (DOT)

Need to translate DOT into concentration

Solubility of oxygen in the fermentation medium must be known.

1. The Sulphite oxidation technique
Measures the rate of conversion of a 0.5M solution of sodium sulphite to
sodium sulphate in the presence of a copper or cobalt catalyst

Cu++ or Co++
Na2SO3 + 1/2 O2 Na2SO4

Oxidation of sulphite is equivalent to the oxygen-transfer rate.

The dissolved oxygen concentration, for all practical purposes, will be zero and
the KLa may then be calculated from the equation:

(where OTR is the oxygen transfer rate)

Disadvantages: i) slow
ii) Rheology of solution not like media
 2. Gassing out techniques
Estimation of KLa by gassing out involves measuring the increase
in dissolved O2 of a solution during aeration and agitation
The oxygen transfer rate will decrease during the period of
aeration as CL approaches C* due to the decline in the driving
force (C* - CL).
To monitor the increase in dissolved oxygen over an adequate
range it is necessary first to decrease the oxygen level to a low
value.
Two methods have been employed to achieve this lowering of
the dissolved oxygen concentration –
 the static method and
the dynamic method.
 The oxygen transfer rate, at
one time, will be equal to
the slope of the tangent to
the curve of values of
dissolved oxygen
concentration against time
of aeration.

The increase in dissolved oxygen concentration of a solution over a period of aeration. The
oxygen transfer rate at time X is equal to the slope of the tangent at point Y.
(i) Static Method
• The oxygen concentration of the solution is lowered by gassing the
liquid out with nitrogen gas, so that the solution is 'scrubbed' free
of oxygen.
• The deoxygenated liquid is then aerated and agitated and the
increase in dissolved oxygen monitored using some form of
dissolved oxygen probe.
• The increase in dissolved oxygen concentration is given by –
dCL / dt = KLa(C*-CL)
The integration of equation yields:

Thus, a plot of In (C* - CL) against time will yield a straight line of slope -KLa
A plot of the In(C* - CL) against time of aeration, the
slope of which equals -KLa.
Advantages:
It is very rapid than sulphite method (15 mins).
 May utilise fermentation medium and dead cells.
Disadvantages:
Use for small scale vessels, there are severe limitations to its
use on large scale fermenters which have high gas residence
times.
The air supply to such a vessel is resumed after deoxygenation
with nitrogen, the oxygen concentration in the gas phase may
change with time as the nitrogen is replaced with air.
(ii) Dynamic Method:
 The respiratory activity of a growing culture in the fermenter utilized to
lower the oxygen level prior to aeration.

 Complex nature of fermentation broths the probe used to monitor the

change in dissolved oxygen concentration must be of the membrane-
covered type which may necessitate the use of the response-correction
factors referred to previously.

 The procedure involves stopping the supply of air to the fermentation which
results in a linear decline in the dissolved oxygen concentration due to the
respiration of the culture.
Dynamic gassing out for the determination of KLa values.
Aeration was terminated at point A and recommenced at point B.
 OTR = dCL / dt = KLa(C*-CL) – xQO2

Where,
• x is the concentration of biomass and
• QO2 is the specific respiration rate (mmoles of oxygen
g-l biomass h- I).
• The term xQO2 is given by the slope of the line AB
Equation may be rearranged as:

CL = -1/KLa{(dCL / dt)+ xQO2}+C*

 The dynamic method for determination of KLa values.

Now from
equation, a plot of
CL versus dCL/dt +
xQO2 will yield a
straight line, the
slope of which will
equal -1/KLa
Advantages:
• Can determine KLa during an actual fermentation
• Rapid technique
• Can use a dissolved oxygen probe of the membrane type

Disadvantages:
• Limited range of dissolved oxygen levels can be studied
• Must not allow oxygen levels to fall below Ccrit
• Difficult to apply technique during a fermentation with a
high oxygen demand
• Relies on measurements taken at one point
 3. The oxygen-balance technique
The KLa of a fermenter may be measured during a
fermentation by the oxygen balance technique which
determines, directly, the amount of oxygen transferred into
solution in a set time interval. The procedure involves
measuring the following parameters-

i. The volume of the broth contained in the vessel, VL

(dm3).
ii. The volumetric air flow rates measured at the air inlet
and outlet, Qi and Qo' respectively (dm3 min-1).
iii. The total pressure measured at the fermenter air inlet
and outlet, Pi and Po, respectively (atm. absolute).
iv. The temperature of the gases at the inlet and outlet, Ti
and To, respectively (K).
v. The mole fraction of oxygen measured at the inlet and
outlet, Yi and Yo' respectively.
The oxygen transfer rate may then be determined from the
following equation-

Advantage:
The oxygen-balance technique appears to be
the simplest method for the assessment of KLa.
It can measure aeration efficiency during a
fermentation.
Disadvantage:
Extra cost of the monitoring equipment.
 FACTORS AFFECTING KLa VALUES IN
FERMENTATION VESSELS
• A number of factors have been demonstrated to affect
the KLa value. Such factors include

• the air-flow rate employed in vessels

• the degree of agitation inside vessels

• the rheological properties of the culture broth

• the presence of antifoam agents.

 Temperature control
• The reactor is to be operated at the optimum temperature of
the organism being cultured.

• The temperature probe senses the temperature existing in the

bioreactor and feeds this data to the temperature control unit.

• The tank will be insulated for efficient heat transfer. Using

electric heating systems is possible, but they can be costly to
operate and cumbersome to maintain or repair.

• Jacket is used to circulated the chilled water or glycol.

Additionally, for a completely independent bioreactor,
incorporating a TCU (temperature control unit) to operate in
closed or constant potable water feed mode will perform quite
efficiently.
Temperature probe
• These are RTD (Resistance Temperature Detector)
sensor that are made from Platinum.

• A resistance temperature detector operates on the

principle of the change in electrical resistance in wire
as a function of temperature.

• The Pt-100 sensor has a resistance of 100 ohms at 0°C

and is by far the most common type of RTD sensor
used.
 pH probe

• Gel filled: To slow the process of diffusion of electrolyte in the

medium

• Pressurized: To prevent the inflow of medium components

during high pressure autoclaving

• Calibrated: Before autoclaving for the correct reading

• Life: The life is about 30-50 autoclave cycles

• Replace the probe if the response is sluggish

 DO probe
• Clark sensors use gold or platinum as the cathode and silver as the anode.
Oxygen is reduced within the sensor when a polarizing voltage is applied to
the cathode. These electrodes require a special meter to provide the
polarizing voltage (usually between –0.7 V to –0.8 V) that causes a
reduction of oxygen. This meter then measures the current flow and
converts it into a signal that can be recorded.

• Galvanic sensors use silver or platinum as the cathode and lead, iron or
zinc as the anode. The reduction of oxygen in the presence of the sensor is
spontaneous and no polarizing voltage is necessary. These electrodes have
an internal 'shorting resistor' so that the current flow is converted to a
voltage signal that can be directly measured.
 Foam sensor
• Foaming is one of the common problems encountered in
industrial fermentations. If foam escapes from the
fermenter, it can wet filters, increasing pressure drop &
decreasing gas flow. It provides a pathway to contaminating
microorganisms to enter the fermenter.

• The control of foam is based on its detection by a

conductance probe in the vessel head space.

• It leads to a controller delivering a dose of liquid antifoam

reagent via a peristaltic pump.

• A delay timer ensures the antifoam reagent has adequate

time to reduce the foam level before another shot of
antifoam is added.
Standard geometry of a stirred tank reactor

• Stirred tanks are usually cylindrical in

shape.
• The base of the tank is rounded at the
edges; this eliminates sharp corners
and stagnant/ dead pockets into
which fluid currents may not
penetrate.
• Typically the STRs have aspect ratio of
1-2. However some of the air lift and
bubble column reactors have higher
aspect ratios on 10-13.
Problem:
• A cylindrical bioreactor has a liquid
volume of 100,000 L. It has an aspect
ratio of 1:1. The height of reactor the
liquid in the reactor will be
appro i atel ….??
 Dimensions of a stirred tank bioreactor
Ratio Typical Remarks
values
Height of liquid in reactor to HL/Ht ~0.7-0.8 Depends on the level of
height of reactor foaming produced during the
fermentation
Height of reactor to diameter Ht/Dt ~1 - 2 European reactors tend to be
of tank taller than those designed in
the USA
Diameter of impeller to Da/Dt 1/3 - 1/2 Rushton Turbine reactors are
diameter in tank generally 1/3 of the tank
diameter. Axial flow impellers
are larger.
Diameter of baffles to diameter Db/Dt ~0.0.08 -
of tank 0.1
Impeller blade height to W/Da 0.2
diameter of impeller
Impeller blade width to L/Da 0.25
diameter of impeller
Distance between middle of E/W 1
impeller blade and sparger to
impeller blade height
Modes for reactor operation

1. BATCH
2. CONTINUOUS
3. FED-BATCH
 BATCH REACTOR/ BATCH CULTIVATION

• Batch cultivation is closed system

where there is no interaction
between the system and the
surrounding during the process.
Except air during the aerobic
cultivation.
• In Batch cultivation we prepare
medium, sterilize it and inoculate the
culture into the bioreactor.
• Allow the cells to grow and produce
the product.
• Once the product formation reaches
maximum harvest the fermentation
broth.
CONTINUOUS REACTOR/ CULTIVATION
 How cells grow during Batch cultivation

After inoculating the medium and start measuring the

biomass at different time intervals, you may find six different
phases. They are
[Link] phase
[Link] phase
[Link] phase
[Link] phase
 BATCH CONTINUOUS
1. The bacteria are inoculated into the 1. The fresh medium flows into the
bioreactor (always stirred tank fermentor continuously, and part of the
bioreactor). medium in the reactor is withdrawn from
2. Then, under certain conditions the fermenter at the same flow rate of the
(temperature, pH, aeration, etc.) the inlet flow.
bacteria go through all the growth phases 2. The bacteria is grown under certain
(lag, exponential, stationary). conditions (temperature, pH, aeration)
Advantages: Advantages:
• can be used for diff reactions every day. • Works all the time: low labor cost, good
• Safe: can be properly sterilized. utilization of reactor
• Little risk of infection or strain mutation • Often efficient: due to the autocatalytic
• Complete conversion of substrate is nature of microbial reactions,.
possible • the productivity can be high.
• Automation may be very appealing.
• Constant product quality
Dis-advantages: Dis-advantages:
•High labor cost •promised continuous production for months
•Much idle time – Sterilization, growth, fails due to a. infection. b. spontaneous
cleaning mutation of microorganisms to non
•Safety – filling emptying, cleaning. producing strain
 Why continuous cultivation is not
used in the industries
• Secondary metabolites are produced only during
the stationary phase. Hence the continuous
cultivation is not suitable for them.
• Maintenance of sterility is very difficult.
• High infrastructure cost is required.
 Fed Batch cultivation
• Batch cultivation have low productivity
• Though continuous cultivation productivity is higher it
cannot be used for secondary metabolites
• Fed batch cultivation is semi open system
• Here nutrients are fed slowly into medium either
continuously or discontinuously in stages.
Residence Time Distributions
in Reactors
 Residence Time Distributions
in Reactors
 The assumption of a perfe tl i ed reactor often falls short
of reality.

 Residence time distributions are used to model the imperfect

mixing behavior of real reactors.

 RTD is basically a probability distribution.

 RTD is characteristic of mixing in a reactor.

 Measurement of RTD
• RTD is measured experimentally by use of an inert
tracer injected into the reactor at t = 0. Tracer
concentration is measured at effluent as a function
of time.
• Tracer must be non-reactive and non-absorbing on
reactor walls/internals.
• Tracer is typically colored or radioactive to allow
detection and quantification.
 Pulse Input RTD Measurement
• An amount of tracer No is suddenly (all at once)
injected into the feed of a reactor vessel with flow
at a steady state.
• Outlet concentration is measured as a function of
time.
feed effluent
reactor

injection detection
Pulse Input RTD Measurement
pulse injection pulse response

C C

- 0 + t - 0 + t

feed effluent
reactor

injection detection
The amount of tracer materialN leaving the reactor
between t and t+t for a volumetric flow rate of is

N  Ctt
where t is sufficiently small time such that the
concentration of tracer C(t) is essentially constant over
the time interval.
Dividing by total amount of tracer injected, No yields
the fraction of material that has a residence time
between t and t+t:

N Ct  Ct 
 t  Et t Et  
No No 
0 Ct dt
where E(t) represents the residence-time
distribution function.
 RTD Characteristics
• E(t) is sometimes called the exit-age distribution
function.
• E(t) is the most often used distribution function for
reactor analysis.
• Fraction of exit stream that has resided in the reactor
for a period of time shorter than a given value of t:
t

 Etdt  Ft
0
• Fraction of exit stream that has resided in the reactor
for a period of time longer than a given value of t:


 Etdt  1  Ft
t
 Mean Residence Time
• Mean residence time- tm
• The mean value of the time is the first moment of the
RTD function, E(t).


 tEt dt 
tm  0

  tEt dt
 Et dt
0
0
 Other Moments of the RTD
• 1st moment – mean residence time

• 2nd moment – variance (extent of spread of the RTD)


   t - t m  Et dt
2 2

0
NON- IDEAL REACTORS DESCRIBED USING-

1. Residence time distribution function, E(t)

2. The cumulative distribution function, F(t)
3. The mean residence time, tm
4. The variance, σ2
TYPES OF BIOREACTORS
 I. THE CONTINUOUS STIRRED TANK REACTOR:
 The continuous stirred-tank reactor (CSTR), also known as chemostat
The liquid or slurry stream is continuously introduced and liquid contents are
continuously removed from the reactor.
 Microbial culture may or may not be introduced to the reactor under normal
operation.
 The basic characteristic of the ideal CSTR is that the concentration of the
substrate and microorganisms are the same everywhere through out the
reactor.

ADVANTAGES :
Continuous operation, less labor intensive

DISADVANTAGES:
Consumption of more power, sterilization,
strain mutation
 II. BUBBLE COLUMN REACTOR
 Reactors with large aspect ratio which essentially take the form of a column
instead of a tank.

 Mixing- forcing compressed gas.

 APPLICATIONS- produ tio of eer, vi egar, aker s east, SCP.

 ADVANTAGES-
1. Low capital cost
2. Simple mechanical configuration
3. Low energy requirements- less operating cost
 III. AIRLIFT BIOREACTOR
 NO AGITATION
 MIXING THROUGH AERATION
 Recirculation of liquid through a downcomer connecting the top and bottom
of the main bubbling section.
 Liquid movement because of difference in density which arises as result of
continuous aeration.
 PARTS
I. Riser- The gas is injected at the bottom of this section, and the flow of
gas and liquid is predominantly upward.
II. Downcomer- parallel to the riser, is connected to the riser at the
bottom and at the top. The flow of gas and liquid is predominantly
downward. The driving force for recirculation is the difference in mean
density between the downcomer and the riser; this difference
generates the pressure gradient necessary for liquid recirculation.
III. Base- does not significantly affect the overall behavior of the reactor,
but the design of this section can influence gas holdup, liquid velocity,
and solid phase flow
IV. Gas separator- This section at the top of the reactor connects the riser
to the downcomer, facilitating liquid recirculation and gas
disengagement.
 TWO TYPES- Internal loop, External loop

ADVANTAGES : APPLICATIONS :
1. No shear and mechanical stress Shear sensitive mammalian and plant cells
2. Efficient heat transfer
3. Simple mechanical design
 IV. THE PLUG FLOW REACTOR
 Plug flow, or tubular, reactors consist of a hollow pipe or tube through which
reactants flow.
 Tubular reactor or a piston- flow reactor.
 The liquid stream continuously enters one end of the reactor and leaves at
the other end.
 In the ideal plug flow reactor (PFR) we envision that flow moves through the
reactor with no mixing with earlier or later entering flows.
 The concentration of substrates and microorganisms vary throughout the
reactor. Highest at the entrance of the reactor, which tends to make rates
there quite high.
APPLICATION: Waste treatment
ADVANTAGES:

1. Can run for long periods of time without maintenance.

2. The heat transfer rate can be optimized by using more, thinner tubes or fewer, thicker
tubes in parallel.

DISADVANTAGES:

1. Temperatures are hard to control and can result in undesirable temperature gradients
2. Expensive to maintain.
 Comparison of possible advantages (+) and Disadvantages (-)
for Batch, CSTR and PFR Reactors .

Criteria Batch CSTR PFR

Simplicity and Cost + + -
Continuous operation - + +
Large throughput - + +
Cleanout + + -
On-line analysis - + +
Product quality - + +
 V. FLUIDIZED BED REACTOR
 Complex reactors
 Three phase systems- solid, liquid and gas.
 Heterogeneous biocatalysts (flocculated organisms, pellets of immobilized enzymes,
cells) are maintained in suspension by a high upward flow rate of the fluid to be treated.
The carriers may be sand grains or granular activated carbon.
ADVANTAGES:
1. Uniform particle mixing
[Link] temperature gradients
3. The ability to operate reactor in continuous state.

DISADVANTAGES:
1. Increased reactor vessel size
2. pumping requirements and pressure drop
3. Pressure loss scenario
 VI. PACKED BED BIOREACTORS
The medium to which the microorganisms are attached is stationary (e.g
plastic media or pea sized stones). Commonly packed bed reactors are used
for aerobic treatment of waste waters and are known as tricking filters and or
biological towers.

ADVANTAGES:
1. There is improved contact between the waste stream and the micro
organisms .