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Bioprrocess Control

A bioreactor is a closed vessel used for producing chemicals and biological reactions, providing essential functions like agitation, aeration, temperature control, and waste removal. Various designs exist, including airlift, tubular, membrane, fluidized bed, packed bed, and photobioreactors, each suited for specific applications in bioprocessing. Key components of bioreactors include aeration systems, impellers, and sensors for monitoring environmental factors, all aimed at optimizing microbial growth and product yield.

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0% found this document useful (0 votes)
6 views20 pages

Bioprrocess Control

A bioreactor is a closed vessel used for producing chemicals and biological reactions, providing essential functions like agitation, aeration, temperature control, and waste removal. Various designs exist, including airlift, tubular, membrane, fluidized bed, packed bed, and photobioreactors, each suited for specific applications in bioprocessing. Key components of bioreactors include aeration systems, impellers, and sensors for monitoring environmental factors, all aimed at optimizing microbial growth and product yield.

Uploaded by

t.tlangdingliana
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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A bioreactor is a type of fermentor vessel that is used for the production of

various chemicals and biological reactions.


It is a closed container with adequate arrangement for aeration, agitation,
temperature and pH control, and drain or overflow vent to remove the waste
biomass of cultured microorganisms along with their products.
A bioreactor should provide for the following:
1. Agitation (for mixing of cells and medium),
2. Aeration (aerobic fermentors); for O2 supply,
3. Regulation of factors like temperature, pH, pressure, aeration, nutrient
feeding, and liquid leveled.
4. Sterilization and maintenance of sterility, and
5. Withdrawal of cells/medium
Bioreactors are used for the production of biomass, metabolites, and antibiotics.
Bioreactor Design
• The design and mode of operation of a bioreactor are based on the
production of an organism, optimum conditions required for desired
product formation, product value, and its scale of production.
• A good bioreactor design will help to improve productivity and provide
higher quality products at lower prices.
• A bioreactor is a device that consists of various features such as an
agitator system, an oxygen delivery system, a foam control system, and a
variety of other systems such as temperature & pH control system,
sampling ports, cleaning, and sterilization system, and lines for charging
& emptying the reactor.
• The material used for the construction of a bioreactor must have the
following important properties:
• It should not be corrosive.
• It should not add any toxic substances to the fermentation media.
• It should tolerate the steam sterilization process.
• It should be able to tolerate high pressure and resist pH changes.
• The sizes of the bioreactor vary widely depending on the application.
• Some bioreactors are designed for small scale fermenters and some for
large scale industrial applications from the microbial cell (few mm3) to
shake flask (100-1000 ml) to the laboratory-scale fermenter (1 – 50 L) to
pilot level (0.3 – 10 m3) to plant scale (2 – 500 m3) for large volume).
Bioreactor Principle
• The bioreactor is the heart of any biochemical process as it provides an
environment for microorganisms to obtain optimal growth and produce
metabolites for the biotransformation and bioconversion of substrates into
desirable products.
• The reactors can be engineered or manufactured based on the growth
requirements of the organisms used.
• Reactors are machines that can be made to transform biological-based
materials into desirable products.
• They can be used for the production of various enzymes and other bio-
catalysis processes.
Parts of the bioreactor and their function
• These reactors have been designed to maintain certain parameters like
flow rates, aeration, temperature, pH, foam control, and agitation rate.
• The number of parameters that can be monitored and controlled is limited
by the number of sensors and control elements incorporated into a given
bioreactor
1. Fermenter Vessel
• A fermenter is a large cylinder closed at the top and bottom connected
with various pipes and valves.
• The vessel is designed in such a way that it allows to work under
controlled conditions.
• Glass and stainless steels are two types of fermenter vessels used.
• The glass vessel is usually used in small-scale industries. It is non-toxic
and corrosion-proof.
• Stainless steel vessel is used in large scale industries. It can resist
pressure and corrosion.
2. Heating and Cooling Apparatus
• The fermentor vessel’s exterior is fitted with a cooling jacket that seals
the vessel and provides cooling water.
• Thermostatically controlled baths or internal coils are generally used to
provide heat while silicone jackets are used to remove excess heat.
• A cooling jacket is necessary for sterilization of the nutrient medium and
removal of the heat generated during fermentation in the fermentor.
3. Aeration System
• An aeration system is one of the very important parts of a fermentor.
• It is important to choose a good aeration system to ensure proper aeration
and oxygen availability throughout the culture.
• It contains two separate aeration devices (sparger and impeller) to ensure
proper aeration in a fermentor.
• The stirring accomplishes two things:
• It helps to mix the gas bubbles through the liquid culture medium
and
• It helps to mix the microbial cells through the liquid culture
medium which ensures the uniform access of microbial cells to the
nutrients.
4. Sealing Assembly
• The sealing assembly is used for the sealing of the stirrer shaft to offer
proper agitation.
• There are three types of sealing assembly in the fermenter:
• Packed gland seal
• Mechanical seal
• Magnetic drives
5. Baffles
• The baffles are incorporated into fermenters to prevent a vortex improve
aeration in the fermenters.
• It consists of metal strips attached radially to the wall.
6. Impeller
• Impellers are used to provide uniform suspension of microbial cells in
different nutrient mediums.
• They are made up of impeller blades attached to a motor on the lid.
• Impeller blades play an important role in reducing the size of air bubbles
and distribute them uniformly into the fermentation media.
• Variable impellers are used in the fermenters and are classified as follows.
• Disc turbines
• Variable pitch open turbine
7. Sparger
• A sparger is a system used for introducing sterile air to a fermentation
vessel. It helps in providing proper aeration to the vessel.
• The sparger pipes contain small holes of about 5-10 mm, through which
pressurized air is released.
• Three types of sparger are used
• Porous sparger
• Nozzle sparger
• Combined sparger–agitator
8. Feed Ports
• They are used to add nutrients and acid/alkali to the fermentor.
• Feed ports are tubes made up of silicone.
• In-situ sterilization is performed before the removal or addition of the
products.
9. Foam-Control
• The level of foam in the vessel must be minimized to avoid
contamination, this is an important aspect of the fermentor.
• Foam is controlled by two units, foam sensing, and a control unit.
• A foam-controlling device is mounted on top of the fermentor, with an
inlet into the fermentor.
10. Valves
• Valves are used in the fermentor to control the movement of liquid in the
vessel.
• There are around five types of valves are used, that is,
• globe valve,
• butterfly valve,
• a ball valve, and
• diaphragm valve.
• A safety valve is built-in in the air and pipe layout to operate under
pressure
11. Controlling Devices for Environmental Factors
• A variety of devices are utilized to control environmental elements like
temperature, oxygen concentration, pH, cell mass, essential nutrient
levels, and product concentration.
12. Use of Computer in Fermenter
• For an efficient process, monitoring, and data collecting, fermentors are
generally coupled with modern automated and semi-automated computers
and databases.
Types of bioreactor
Airlift bioreactors are tower reactors for large-scale aerobic cultures where the
mixing of the culture broth is done by the inserted gas via an airlift pump.
The airlift bioreactor uses the jet function of air and the difference in fluid
density to cause the reaction liquid to circulate, so as to achieve the stirring,
mixing and oxygen transfer of the liquid. That is, without mechanical stirring, it
completely relies on the gas to cause the liquid to circulate and generate
turbulence, thereby achieving the purpose of gas-liquid mixing and transfer.
Compared with traditional stirred tank reactors, airlift bioreactors have better
performance and effect in the gas-liquid mass transfer process.It have obvious
advantages and have been widely used in the production of SCP, filamentous
fungi, and wastewater treatment.
The structure of airlift bioreactor is relatively simple, does not require stirring,
is easy to clean and maintain, is not easy to be contaminated, has low energy
consumption, and has high dissolved oxygen efficiency. In addition, the it has
low operating and construction costs.
Airlift bioreactors have several significant advantages over stirred tank reactors.
First, the airlift bioreactor can provide a larger gas-liquid contact area, increase
the gas-liquid mass transfer efficiency, and help fully meet the oxygen needs of
cells. Secondly, the liquid flow generated by the movement of bubbles in the
airlift bioreactor promotes cell mixing and reduces the difference in the local
liquid environment.
This is important for uniform growth of cells and uniform distribution of
products. In addition, the airlift bioreactor reduces the shear force and
mechanical stress that cells receive, which is beneficial to cell growth and the
stability of biological reactions.
However, airlift bioreactors also have some challenges and limitations. First, the
structure of it is relatively complex, involving key technologies such as gas
distribution and pressure control. Second, the selection of bubble size in airlift
fermenters has an important influence on the gas-liquid mass transfer efficiency
and cell growth conditions, and requires systematic optimization. In addition,
the airlift fermenters also needs to consider the influence of parameters such as
the density of suspended cells, gas intake, and stirring speed in specific
operations.
Although there are some technical challenges in airlift bioreactors, it is still a
widely used type of suspended cell culture bioreactor. Airlift reactors improve
cell growth and the efficiency of biological reactions by optimizing the gas-
liquid mass transfer process, providing strong support for the development of
biopharmaceuticals, biofuels, and other bioprocesses.
Airlift bioreactors are used in various applications where gentle mixing and
efficient gas transfer are needed, particularly in the production of
biopharmaceuticals, biofuels, and for wastewater treatment. They are suitable
for culturing shear-sensitive cells and for processes where reactants or products

are in gaseous form.

Tubular bioreactor
A tubular bioreactor is a type of bioreactor that operates on the principle
of continuous flow through a cylindrical or tubular vessel. Reactants are
continuously introduced, undergo a biological reaction within the tube, and the
resulting products are then continuously removed. This system promotes a plug
flow, meaning minimal backmixing and a high production capacity per unit
volume.

A tubular bioreactor is a type of bioreactor that operates on the principle of


continuous flow through a cylindrical or tubular vessel. Reactants are
continuously introduced, undergo a biological reaction within the tube, and the
resulting products are then continuously removed. This system promotes a plug
flow, meaning minimal backmixing and a high production capacity per unit
volume.
• Continuous Flow: Reactants (often a mixture of liquid, gas, and/or solid)
are continuously introduced into one end of the tubular bioreactor.
• Reaction Zone: As the reactants flow through the tube, a biological
reaction takes place, driven by microorganisms, cells, or enzymes.
• Plug Flow: Ideally, the flow is a "plug" or piston-like, meaning there's
minimal mixing or backmixing between the incoming and outgoing
streams. This allows for a more predictable reaction rate and product
distribution.
• Product Collection: The products of the reaction are continuously
removed from the other end of the tube.
• Versatile Applications: Tubular bioreactors can be used in a variety of
bioprocesses, including wastewater treatment, solid substrate
fermentation, photobioreactors (using light for photosynthesis), and the
production of various biological products.
• Advantages:
High Production Capacity: The continuous nature of the process allows for a
high throughput of products per unit volume.
Reduced Backmixing: Minimal backmixing helps maintain consistent reaction
conditions and prevents unwanted side reactions.
Flexibility: Tubular bioreactors can be designed to accommodate various
reaction rates and flow velocities.
Disadvantages:
o Long Pipelines: For reactions with very low rates, the required
length of the tubular reactor can become impractical.
o Backmixing Issues: In real-world applications, some backmixing
can occur, Tubular bioreactors have practical applications in
diverse fields, including waste water treatment, algae cultivation in
photobioreactors, and bioprocesses involving solid substrates. They
can also be used in biological tissue processes, making them
versatile for various applicationswhich may affect the homogeneity
of the reaction and the product.

Membrane biorecators
Membrane filtration involves the flow of watercontaining pollutants across a
membrane. Water permeates through the membrane into a separate channel for
recovery . Because of the cross-flow movement of water and the waste
constituents, materials left behind do not accumulate at the membrane surface
but are carried out of the system for later recovery or disposal. The water
passing through the membrane is called the permeate, while the water with the
more-concentrated materials is called the concentrate or retentate.
Membrane Bioreactors combine conventional biological treatment
(e.g. activated sludge) processes with membrane filtration to provide an
advanced level of organic and suspended solids removal. When designed
accordingly, these systems can also provide an advanced level of nutrient
removal. In an MBR system, the membranes are submerged in an aerated
biological reactor. The membranes have porosities ranging from 0.035 microns
to 0.4 microns (depending on the manufacturer), which is considered between
micro and ultrafiltration.
This level of filtration allows for high quality effluent to be drawn through the
membranes and eliminates the sedimentation and filtration processes typically
used for wastewater treatment. Because the need for sedimentation is
eliminated, the biological process can operate at a much higher mixed liquor
concentration. This dramatically reduces the process tankage required and
allows many existing plants to be upgraded without adding new tanks. To
provide optimal aeration and scour around the membranes, the mixed liquor is
typically kept in the 1.0-1.2% solids range, which is 4 times that of a
conventional plant.

Fluidized bed reactor


• Fluid bed bioreactors constitute packed beds with smaller particles. This
prevents problems such as clogging, high liquid pressure drop,
channeling, and bed compaction associated with packed bed reactors.
• Catalyst is laid on the bottom of the reactor and the reactants are pumped
into the reactor through a distributor pump to make the bed fluidized.
• In these reactors, the cells are immobilized small particles which move
with the fluid as a result, mass transfer, oxygen transfer, and nutrition to
the cells are enhanced.
• The bioreactors can be used for reactions involving fluid-suspended
biocatalysts, such as immobilized enzymes, immobilized cells, and
microbial flocs.
• Its main advantages include its ability to maintain even temperatures,
easy replacement and regeneration of the catalyst, continuity, and
automaticity of operation, and reduced contact time between gas and
solid, compared to other catalytic reactors.
Packed bed reactors
Packed bed fermentor
• A packed bed fermentors is a bed of solid particles, having biocatalyst on
or within, the matrix of solids.
• It can either be run in the submerged mode (with or without aeration) or
the trickle flow mode.
• Frequently used in chemical processing processes such as absorption,
distillation, stripping, separation process, and catalytic reactions, packed
bed reactors are also called fixed bed reactors.
• In packed-bed bioreactors, the air is introduced through a sieve that
supports the substrate.
• This reactor has many benefits, like a high conversion rate for the
catalyst, ease of operation, low construction and operation costs,
increased contact between reactant and catalyst, and the ability to work
in high temperatures and pressures.
Photobioreactors

• A photobioreactor is a specialized unit for fermentation that is either


illuminated by direct sunlight or artificially illuminated
• They are made up of glass or more commonly transparent plastic and the
tubes or flat panels is consist of light receiving systems.
• In this bioreactor, centrifugal pumps or airlift pumps can be used to
circulate the medium through solar receivers.
• Photo-bioreactors are usually operated in a continuous mode at a
temperature in the range of 25–40 °C.
Photobioreactors are used for the photosynthetic culture of microalgae

and cyanobacteria to produce products such as astaxanthin and β-
carotene.
Down stream pprocessings
• Downstream processing refers to unit operations that isolate, purify, and
concentrate the product. Downstream processing often determines
the economic feasibility of the process.
• Downstream processing constitutes a critical step in the manufacturing of
pharmaceuticals such as antibiotics, hormones, antibodies and vaccines
and enzymes with regard to product purity, cost, and environmental
impact.
• Downstream processing includes processes required to take biological
materials such as cells and derive from them a pure product. The various
steps of downstream processing involve:
• Separation, Cell disruption, Extraction, Isolation, Purification,
Polishing,Virus filtration/inactivation, Concentration
The first step of DSP and usually involves the separation of solids substances,
from the liquid media.
Either of the following ways achieves it:

Different techniques of filtration are as follows:

1. Surface filtration
2. Depth filtration
3. Centrifugal filtration
4. Rotating drum vacuum filtration
Filtration
Filtration is a crucial step in the downstream processing of all types of cell
harvesting process since it is also integral to the capture of unwanted impurities,
intermediate purification of the sample, and polishing stages. Moreover,
filtration is utilized for the preparation of purified water and other liquids for
buffering and sanitizing purposes.

Different types of filtration process:


• Microfiltration can be used at the start of the downstream process to
clarify the feed beyond what was accomplished in the upstream harvest
and centrifugation/clarification.
• Ultrafiltration is used between chromatography steps to concentrate the
product and change the buffer conditions to prepare it for subsequent
chromatography steps.
• Sterilizing grade direct flow filtration involves the use of nanofiltration
cartridges to eliminate microbial organisms and insoluble proteins, to
remove adventitious and endogenous viruses, and to serve as a sterile
filtration process to the product in preparation for final formulation.

Centrifugation– It may be used for bacteria, usually, protein precipitates.


Centrifugation is one of the most frequently used methods to efficiently separate
molecules with different densities through the use of centrifugal force. This
process utilizes a high speed rotor that will outwardly move the solid particles
from the axis of rotation at a selected speed or revolution per minute (RPM).

This method uses the principle of sedimentation where the centripetal


acceleration causes much denser substances to move outward while the less
dense materials are displaced towards the center.
Types of Centrifugation Methods
• Differential Pelleting: This is the simplest centrifugation type employed
wherein particles in a suspension will sediment at different rates based on
their different densities. This method is commonly used for cellular
harvesting or when producing crude subcellular fractions from tissue
homogenate. The downside of this method lies with the heterogeneity of
biological particles which can cause contamination and poor recoveries.
But this can be further addressed through resuspension and repeating of
the centrifugation steps.

• Density Gradient Centrifugation: This method is mainly used for the


separation of particles form living cells. But in theory, it can be applied in
particle separation of materials with less than 20µm diameter. Density
Gradient Centrifugation is a procedure for separating particles in which
the sample is placed on a preformed gradient like sucrose or caesium
chloride.
1. Rate-Zonal Centrifugation: In this type of method, the cross-
contamination risk seen in the former method can be avoided
through layering the sample as a narrow zone on top of a density
gradient. With this, the faster sedimenting particles will not be
contaminated by the much slower ones. However, the disadvantage
with this technique is the limitation on sample volume that can be
accommodated on the density gradient.

Rate-zonal centrifugation method uses the size and mass of the


particles in order to sediment, not density. With the movement of
particles down through the density medium, zones will form with
similar sized particles. If centrifuged long enough, the particles will
form a pellet based on the fact that the particles density is greater
than that of the gradient.

2. Isopycnic Centrifugation: This method is also known as buoyant or


equilibrium separation where particles are separated based solely
on their density. The sizes of particles only affect the rate at which
they move until their density is the same as the surrounding
gradient medium. IT must be noted that the density of the gradient
medium must be greater than that of the particles to be separated.

Flocculation and flotation– It is used for small bacterial cells which are
difficult to separate even by centrifugation.
Flocculation: It involves the aggregation of cells which may be induced by
inorganic salt, minerals, hydrocolloids and organic polyelectrolytes.
If flocculation isn’t effective than very minute gas bubbles is made by sparging,
release of over pressure or electrolysis.
Flotation: in any case, the gas bubble need to adsorb and surround the cell,
raising the gas bubbles to the surface of media in the form of foam.

Cell disruption
Disruption of microbial cell is usually difficult because of their small size, rigid
cell walls and high osmotic pressure inside the cells.
Disruption of cell is generally achieved by mechanically, lysis or drying:

1. Mechanical cell disruption: this involves the uses of shear, E.g.-,


colloid mill, ball mill grinder etc., homogenizer and ultrasound.
2. Drying: it involves the drying of cells by adding the cells into a
huge amount of cold acetone and extracted using buffer or salt
solution.
3. Lysis: lysis of microbial cells may be achieved by chemical means,
e.g., salt or surfactants, osmotic shock, freezing, or Lytic enzymes,
e.g., lysozyme, etc.

4. Precipitation
Precipitation is the most used technique in industry for the concentration
of macromolecules such as proteins and polysaccharides. • Precipitation
technique can also be employed for the removal of certain unwanted
byproducts e.g. nucleic acids, pigments. • Neutral salts, organic solvents,
high molecular weight polymers (ionic or non-ionic), besides alteration in
temperature and pH are used in precipitation. • In addition to these non-
specific protein precipitation reactions (i.e. the nature of the protein is
unimportant), there are some protein specific precipitations e.g., affinity
chromatography
Ammonium sulfate precipitation is the most commonly used technique
for purification of proteins both at laboratory and large scales. It is based on
alteration of protein solubility in the presence of ammonium sulfate. The
solubility of the protein increases in addition to ammonium sulfate (<0.15 M), an
effect called salting in. At higher concentrations of this salt, protein solubility
usually decreases, resulting in precipitation of protein, this effect is called salting
out. The salting-out mechanism is based on preferential solvation due to
exclusion of the co-solvent (salt) from the hydration layer.
Ammonium sulfate precipitation enables quick precipitation of cellular proteins.
Hence it is generally useful for initial steps of purification

Liquid-liquid extraction
. Liquid-Liquid Extraction: The concentration of biological products can
be achieved by transferring the desired product (solute) from one liquid
phase to another liquid phase, a phenomenon referred to as liquidliquid
extraction. Besides concentration, this technique is also useful for partial
purification of a product. The efficiency of extraction is dependent on the
partition coefficient i.e. the relative distribution of a substance between
the two liquid phases. The process of liquid-liquid extraction may be
broadly categorized as extraction of low molecular weight products and
extraction of high molecular weight products.

CHROMATOGRAPHY
• Chromatography is basically an analytical technique dealing with the
separation of closely related compounds from a mixture. Chromatography
usually consists of a stationary phase and mobile phase.
• Chromatography separates substances in a mixture based on their
differential interaction with a stationary and a mobile phase. The mobile
phase carries the sample through a stationary phase, and different
components in the mixture interact with the stationary phase to different
extents, leading to their separation. This separation occurs because of
differences in how each component partitions or adsorbs between the two
phases.
• Different types of chromatopgraphy are used in dsp of compounds
Lyophilization
Lyophilization is a water removal process typically used to preserve perishable
materials, to extend shelf life or make the material more convenient for
transport. Lyophilization works by freezing the material, then reducing the
pressure and adding heat to allow the frozen water in the material to sublimate.

1. Lyophilization occurs in three phases, with the first and most critical
being the freezing phase. Proper lyophilization can reduce drying times
by 30%.
2. Freezing Phase
3. There are various methods to freezing the product. Freezing can be
done in a freezer, a chilled bath (shell freezer) or on a shelf in the
freeze dryer. Cooling the material below its triple point ensures that
sublimation, rather than melting, will occur. This preserves its physical
form.
4. Lyophilization is easiest to accomplish using large ice crystals, which
can be produced by slow freezing or annealing. However, with
biological materials, when crystals are too large they may break the
cell walls, and that leads to less-than-ideal freeze drying results. To
prevent this, the freezing is done rapidly. For materials that tend to
precipitate, annealing can be used. This process involves fast freezing,
then raising the product temperature to allow the crystals to grow.
5. Primary Drying (Sublimation) Phase
6. Lyophilization’s second phase is primary drying (sublimation), in
which the pressure is lowered and heat is added to the material in order
for the water to sublimate. The vacuum speeds sublimation. The cold
condenser provides a surface for the water vapor to adhere and
solidify. The condenser also protects the vacuum pump from the water
vapor. About 95% of the water in the material is removed in this phase.
Primary drying can be a slow process. Too much heat can alter the
structure of the material.
7. Secondary Drying (Adsorption) Phase
8. Lyophilization’s final phase is secondary drying (adsorption), during
which the ionically-bound water molecules are removed. By raising
the temperature higher than in the primary drying phase, the bonds are
broken between the material and the water molecules. Freeze dried
materials retain a porous structure. After the lyophilization process is
complete, the vacuum can be broken with an inert gas before the
material is sealed. Most materials can be dried to 1-5% residual
moisture.

Spray drying
The spray drying process involves the atomization of a solution, slurry, or
emulsion containing one or more components of the desired product into
droplets by spraying followed by the rapid evaporation of the sprayed
droplets into solid powder by hot air at a certain temperature and
pressure.
Spray-drying is a technique based on the transformation of a fluid into a
dry powder by atomization in a hot drying gas stream that is generally air .
The spray-drying process consists of four fundamental steps: (i)
atomization of the liquid feed, (ii) drying of spray into drying gas, (iii)
formation of dry particles and (iv) separation and collection of the dry
product from the drying gas . First, the fluid is fed into the drying chamber
by a peristaltic pump through an atomizer or nozzle that can be a rotary
atomizer, a pressure nozzle or a two-fluid nozzle and the atomization
occurs by centrifugal, pressure or kinetic energy, respectively . The small
droplets generated (micrometer scale) are subjected to fast solvent
evaporation leading to the formation of dry particles that are separated
from the drying gas by means of a cyclone that deposes them in a glass
collector situated in the bottom of the device .
Biosensors and applications
Biotechnological processes are dynamic and involve continuous changes
to the physicochemical conditions of the medium. This in turn influences
the functioning of the biocatalyst. The response to changes in the process
environment is less reproducible making the tasks of process development,
optimization and scale-up difficult. Furthermore, bioprocesses inherently
are batch-oriented. Individual process steps need to be optimized and
improved upon to adapt to the progress in process technology. This needs
factual insight of the process state and understanding of the biochemical
and metabolic control mechanisms. Production of recombinant protein is a
fast growing area and the requirements of bioprocess monitoring and
control in such processes is crucial for selecting optimal expression
conditions. These emphasize the requirement of better tools and systems
for online monitoring and control with insight into biochemical variables
in the bioprocess. Automation and process monitoring ensures adherence
to standards and regulations and generates much related process
documentation [2, 3]. The need for quality monitoring is higher for
biotechnological applications which involve intense downstream
processing steps. Furthermore, it is significant from the point of view of
environmental control and food safety. This ensures better process
engineering, stringent quality and optimized processes.
Biosensors in Bioprocessing: Revolutionizing Process Monitoring
Biosensors are revolutionizing bioprocessing by providing real-time, in-line
monitoring of critical parameters. These devices integrate a biological
recognition element, such as an enzyme, antibody, or nucleic acid, with a
transducer that converts biological signals into measurable electrical, optical, or
chemical signals.
In bioprocessing, biosensors offer several key advantages:

• Real-time monitoring: Traditional offline analytical methods are time-


consuming and can introduce delays in process adjustments. Biosensors
provide continuous, real-time data on key parameters like metabolite
concentrations, cell viability, and product formation. This enables
proactive process control and optimization.
• Improved process control: Real-time data from biosensors allows for
dynamic adjustments to process parameters, such as pH, temperature, and
nutrient feed rates, leading to enhanced process efficiency and reduced
variability.
• Enhanced product quality: By continuously monitoring critical quality
attributes, biosensors help ensure product consistency and quality
throughout the production process.
• Reduced costs: Real-time monitoring can minimize off-spec batches,
reduce the need for extensive offline testing, and optimize resource
utilization, leading to significant cost savings.

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