BIOREACTOR CONTROL SYSTEM

Introduction

Bioreactor refers to a vessel which carried out a chemical process which involves organisms or

biochemically active substances derived from such organism. Consider as the most important

item in Bioprocessing, it can be classified by various criteria, which is;

a) Type and form of biocatalyst: free cell in submerged culture; carried bound or

immobilized cells/enzymes; retention of recirculation of the biocatalyst.

b) Configuration: tank (height/diameter <3), column(height/diameter>3).

c) Energy input and aeration: liquid phase; gas phase; combined.

d) Hydrodynamics: perfect mixing; partial mixing; no mixing.

e) Mode of operation: batch, continuous, fed batch .

Type of Bioreactors

These are few types of bioreactor use in the industries:

a) Stirred Tank Bioreactor (STB)

• In this reactor, mechanical stirrers (using impellers) are used to mix the reactor to

distribute heat and material (such as oxygen and substrate).

• Homogenization, suspension of solid, dispersion of gas liquid mixtures, aeration

of liquid and heat exchange.

• Provided with a baffle and a rotating stirrer is attached either at the top or at the

bottom of the bioreactor.

• Baffles are usually flat vertical plate whose width is about one-tenth of the vessel

diameter. Normally, 4-6 baffles plates are fitted to the inside vessel walls to aid

mixing and mass transfer by increasing turbulence, preventing vortex formation

and eliminating ‘dead spaces’.

• Within each vessel the impeller is connected to an external motor, which drives

the stirrer system.

• The agitator assembly, including the seal, is often a potential route of

contamination. To prevent this problem, the shaft has to pass into the fermenter

through as set of aseptic seals. There are specific regulation regarding the

numbers and type of seals. For certain fermentations, two or three seals are

required to minimize the fermenter contamination, and release microorganism and

their products into environment.

• The effectiveness of agitation depends upon the design of impeller blades, speed

of agitation and the depth of liquid. Most STRs have height-diameter aspect ratio

3:1 to 4:1. STRs must create high turbulence to maintain transfer rates, but this

also generates considerable shear force that is detrimental to certain bacteria.

• The typical decision variables are: type, size, location and the number of impeller;

sparger size and location. These determine the hyrdrodynamic pattern in the

reactor, which in turn influence mixing time, mass and heat transfer coefficients,

shear rates etc.

• The conventional reactor is carried out in a batch mode; it is simple in design and

easier to operate.

• This type of reactor are preferable since there will be a minimal loss in case of

contamination or any substandard product formation. Still they suffer the low

volumetric productivity. The downtimes are large and unsteady state fermentation

impose stress to the microbial cultures due to the nutritional limitation.

• Fed batch has been adopted in order to overcome this problems, which offers

excellent mixing and good mass transfer rates. Furthermore, the cost of operation

is lower with the availability usage of variety microbial species.

• Since it is commonly use in chemical industry the mixing concept are well

develop. But STR with immobilized cell is not favored generally due to the

attrition problem; however the system will be successfully operated by separating

the zone of mixing from the zone of cell culturing.

 Design of Stirred Tank Reactor

b) Air Lift Bioreactor ( ALB)

• Generally classified as pneumatic reactor without any mechanical stirring

arangements for mixing and use of the expression of compress gas to bring about

mixing.

• The turbulence caused by the fluid flow ensures adequate mixing of liquid.

• The draft tube is provided in the central section of reactor.

• The introduction of the fluid(air/liquid) cause upward motion and results in

circulatory flow in the entire reactor . The air/liquid velocity will be low and

hence energy consumption is also low.

• Can be use for both free and immobilized cell and there are very few reports on

it’s metabolite production.

• The advantage are the elimination of attrition effects generally encountered in

mechanical agitated reactors. Ideally suited for aerobic culture since oxygen mass

transfer coefficient are quite high in comparison to stirred tank reactor.

Air Lifter Reactor design

c) Fluidized Bed Reactor (FBB)

• Most of it developed for biological systems involving cells as biocatalysts are

three phase system (solid, liquid & gas).

• Generally operated in co-current upflow with liquid as continous phase and other

more unusual configurations like the inverse three phase fluidized bed or gas solid

fluidized bed are not much more importance . Usually fluidization is obtained

either by external liquid recirculation or by gas fed to the reactor.

• Usually in the case of immbolized enzymes, two-phase system involving solid

and liquid but the use of aerobic biocatalyst necessitate introduction of gas (air) as

the third phase.

• A differentiation between the three phase fluidized bed and the airlift bioreactor

would be made on the basis that the katter have a physical internal arrangement

(draft tube), which provides aerating and non aeratiing zones.

• The inculrcilatory motion of the liquid is induced due to the draft tube.

• Basically there are three different types of particles use in FBB :

i. Inert core on which biomass is created by cell attachment.

ii. Porous particles in which biocatalyst is entrapped.

iii. Cell aggregates/flocs (cell immobilized)

• Compare to the conventional mechanically stirred reactors, it provide much lower

attrition of solid particles.

• The biocatalyst concentration can significantly be higher and washout limitation

of free cell sstems can be overcome.

 • The volumetric productivity attained in FBBs is usually higher than in stirred tank

and packed bed bioreactor.

• It can also operated with smaller size particles without drawbacks of clogging,

high liquid pressure drop, channeling and bed compaction. The smaller particle

size is facilitates higher mass transfer rates and better mixing.

d) Packed Bed Bioreactor

• Also known as fixed bed bioreactor are commonly used with attached biofilms

especially in wastewater engineering.

• It’s used gained importance after thepotential of whole cell immobilization

technique has been demonstrated. The immobilized biocatalyst is packed in

column and fed with nutrients either from top or bottom.

• One of the disadvantage is the changed flow characteristic due to alterations in the

bed porosity during operation.

• Packed bed reactor are generally used where substrate inhibition governs the rate

of reactions . And it is widely used with immobilized cells.

 Packed-bed Fermentor

Control system

The control system is the most part in a bioreactor, the whole process would not be able to take

place without it. Optimal catalytic activity should be allowed inside the bioreactor’s environment

due to the high requirement of the microorganism cultivation process. In order to provide such

desired environment, system properties must be monitored and control action taken to rectify any

deviations from the desired values. All this despite that the fact is that almost all bioreactors

monitor and regulate the same values actually invariably. The active area of research is the

fermentation monitoring and control, which aimed to improving the performance of the

bioprocesses and achieving uniform and reliable fermenter operation.

Basically, there are various level of process control in the fermentation industry, but the simplest

one is the manual control that requires human to manipulate devices such as pumps, motors and

valves. While the automatic feedback control is used to maintain parameters at specified values.

There is also scope for implementing advanced control and optimization strategies based on

fermentation models.

The monitoring and control scheme of a typical fermentation process

Process control

Process control is concerned with making adjustment to the process based upon measuring one

or more variables that change as a result of the process function using the component such as:

a) Sensors

b) Controllers

c) Actuators (final element)

d) Process controllers

e) Manual controls

f) Automated controllers

g) Feedback controllers

Feedback controllers

Feedback controllers compare the measured value of the process variable that must be controlled

with its set point and adjust an actuator in order to suppress the deviation between the measuring

value and set point.

Automatic control systems

The controller output change is proportional to the input signal created by the environment

change error that was detected by the sensor.

Integral controllers

The integral controller output signal is determined by the integral of the error over operating

time.

Derivative controllers

Derivative controllers sense the rates of the change of an error signal and contribute an output

signal component that is proportional to the derivative of the error signal.

Feed-forward controllers

Feed-forward controllers employed the measured variable(s) other than the process variable that

must be controlled to carry out an action.

Adaptive bioreactor controls

Mostly applied in systems where process variables characteristics are not known and can not be

measured directly, or when the bioprocesses’ static or dynamic behavior changes with time. The

adaptive controller can either use online measured process data, a theoretical model, or

combination of these to predict the change in the static or dynamic behavior of the process.
Complex bioreactor controls

Computer applications in fermentation technology include data logging, data analysis, process

control, process data logging, and data analysis.

Monitor control system

Parameters such as temperature, pH, dissolved-oxygen concentration, medium flow rate, stirrer

speed and sparging rate have a significant effect on the outcome of fermentation and enzyme

reactions and were monitored and controlled by the bioreactors.

a) Temperature

• Important parameter in fermentation – temperature deviation by a couple of

degrees is able to diminish dramatically the growth and biosynthesis productivity

in cultivation of many microorganisms.

• Commonly monitored cultivation temperature with accuracy not less than

±0.50°C, stainless steel Pt100 sensor usually use to measure the temperature.

• The temperature of bioreactor in the laboratory is usually controlled by one of this

way:

i. A heater is located inside the vessel, and cooling is ensured y thin-wall

pipes located in the upper cover, which are connected with an

electromagnetic valve with the cooling water.

ii. Heating and cooling is proceed in a thermostat, and this thermostat water,

with the help of a pump, circulates through the bioreactor jacket.

 • Variant 1 is less complicated; it ensures a more economic constructive solution.

Works very well for smaller bioreactors with the volume up to 5 liters.

• Variant 2 ensures a more even distribution of heat throughout the bioreactor

volume, which is essential for microorganisms’ cultivation.

• The main reason for the regulation inaccuracy in temperature regulatory process

is the incorrectly chosen PID parameters. This manifest itself as temperature

oscillations.

• The main obstacle in regulating the precise temperature is often, the too high

minimal portion of the cooling water. The valves in the cooling water supply line

should be adjusted correspondingly. Another factor will be the area and density of

the heat surface, since the higher is inertia, the more difficult to reach a higher

accuracy.

b) pH

• Based on the comparison of adjusted ‘set point’ and the real values of pH.

• Practically only sterilisable electrode (most often, ‘Mettler-Tolede’ electrodes) are

used in measuring pH.

• The pH values control is being ensured with the help of peristaltic

pump( commonly used are the silicon tube), correspondingly metering out the

acid and alkali.

 • The ‘set point’ adjustment normally consists of the lower pHmin and the higher

pHmax value. No influence will occur if pH is between these values. Such

adjustment to the pH ‘set point’ is applied to prevent the overdose of the titration

solution. On the other hand, the ‘narrow’ regulation limits of the pH are not

necessary to for the successful course of the cultivation process. It should be

mentioned that the pH measurements should be accurate (±0.02 pH units), since

the dynamics of pH values’ changes provides valuable information on the process

kinetics.

c) pO2 (partial pressure of dissolved oxygen)

• One of the most specific aspects of the fermentation monitoring and

characteristically only for fermentation processes.

• These are few different principles of pO2 control:

i. Varying the mixer’s rotational speed n, assuming that pO2 ~ n.

ii. Combining the change of the mixer’s rotation speed n and the amount of

the inlet compressed air Q. It is assumed that pO2 ~ n, pO2 ~ Q. First of

all, n is usually regulated until it reaches one of the limiting values – nmin

or nmax, and it’s regulation is realized by varying Q. If n and Q have

 reached the limiting values, but pO2 is not within the necessary limits,

then the regulating effect does not occur.

iii. Feeding up the substrates or its any component. It is assumed that pO2 is

proportional to the feeding up intensity. Feeding up is normally realized

with controlled peristaltic pumps. This way, is sometimes combined with

the regulation of the mixer’s rotational speed n, and the oxygen or air

supply flow Q.

• The following should be taken into account, when adjusting the parameter in the

pO2 regulation:

i. pO2 is commonly adjusted in % from the fixed one. It has a value of lower

and upper limit and the different between both these limit is usually 10%-

20%.

ii. Control limit of the mixer’s rotational speed n:nmin and nmax are the

important parameter in pO2 control. It means that, n will vary only in

within this range, when controlling pO2. These limits are determined in

connection with the eliminating of different undesirable phenomena:

1. nmin choice is determined:

a. to secure the minimal partly turbulence mixing level;

b. by the guaranteed bubble dispersion;

c. by the prevented sedimentation.

 2. nmax choice is determined:

a. setting in of the intensive foaming regime;

b. irreversible mechanical damages of cell ;

c. Liquid surface fluctuation and evaporation.

d) Foam

• Its appearance is very undesirable in the process, but during the foaming, it is not

possible to perform high quality analyses and measurement.

• There are 2 methods or their combination that are commonly used to eliminate the

forming of foaming:

i. Based on the information provided by the sensor, additional metering of

an antifoam. The given impulse are relatively very low, with long pause

and a limited metering time. In order to avoid overdose, this additional

control is very necessary, in this case, the mass exchange parameters can

decrease dramatically.
 ii. Mechanical metering of foam. For this purpose, in the bioreactor’s upper

cover has been installed with an upper drive with a special disk-type or

other type of the mechanical foam breaking mixer. If an intensive foaming

begins, then the mechanical breaking of foam will not help any more.

• The combination of both parameters is the optimal solution for this matter. The

application of Variant 1 is more widely use in laboratory bioreactors.

Conclusion

Process monitoring and control stands at the leading edge of bioreactor development. Progress in

bioanalytical chemistry resulted in a vast array of probes, biosensors, and detectors, which enable

the process engineer to screen of myriad of growth parameter. A bioprocess’s financial success is

directly related to its level of process control sophistication, and it is expected, therefore, that

many future bioreactor development will be in the area of process monitoring and control.

Process monitoring and control systems can be readily adapted to any size bioreactor, the only

limitation being the number of such devices the vessel can physically accommodate.
References :

• www.bionewsonline.com

• www.rocw.raifoundation.org/biotechnology

• www.bioreactor.net

• Bioprocess Engineering Principles, Pauline M. Doran, 1995, Academic Printing.

• Producing Biomolecular Substances with Fermenters, Bioreactors, and Biomolecular

Synthesizers. William L. Hochfeld, Taylor & Francis Group.

 Bioreactor and Bioprocessing

(BIO310)

Bioreactor control system and monitoring

Group members:
AINUN NADIAH A BAKAR 2007060159

SAHFUTDIN SUAIDI 2007060138

FARIDAH PARID 2007060160

RAJA ABDUL RAHMAN 2007060081

NURFARIHAH M RAOS 20007060104