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Bio Chem Engg Data-1 (2) - 1
Bio Chem Engg Data-1 (2) - 1
Engineering
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Bioreactors
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Bioreactors
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Bioreactors: Types
On the basis of mode of operation, these are classified into
three classes
Batch reactors
Semi-batch reactors
Continuous reactors
On the basis of design and working mechanism, these are
classified into following major classes
Mechanically stirred (agitated) tanks (vessels).
Bubble columns – that is, cylindrical vessels without
mechanical agitation, in which gas is bubbled through a
liquid.
Packed-bed reactors (tubular reactors).
Membrane reactors, using semi-permeable membranes,
usually of sheet or hollow fiber-type.
. Micro-reactors. 5
Bioreactors: Types
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Bioreactors: Types
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Bioreactors: Effects of Mixing on Reactor Performance
+ =0
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Bioreactors: Effects of Mixing on Reactor Performance
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CSTR( Continuous stirred tank reactor)
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CSTR: Working and Applications
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CSTR: Construction
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Image taken from http://encyclopedia.che.engin.umich.edu/Pages/Reactors/CSTR/CSTR.html Stirrers
CSTR: Advantages and disadvantages
Advantages
Continuous operation of the bio-reactor can increase the
productivity of the reactor significantly.
It is also easy to automate in order to reduce labor costs.
Good temperature control
Easily adapts to two phase runs
Simplicity of construction
Easy to clean
Disadvantages:
low conversion per unit volume
Channeling is possible with poor agitation.
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CSTR: Applications
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CSTR: Working Equations
(1)
XA = conversion at time t
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CSTR: Working Equations
𝐹
𝐴 0 =𝐹 𝐴 0 − 𝐹 𝐴 0 𝑋 𝐴 +(− 𝑟 ¿¿ 𝐴).𝑉 ¿
𝑋𝐴
𝑉 =𝐹 𝐴 0 (2)
(−𝑟¿¿ 𝐴)¿
So for a required conversion and known rate of reaction, volume of reactor
can be determined using eq (2).
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Class activity
𝑽
=𝟎 . 𝟒𝟕𝟓 𝐦𝟑
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Plug Flow Reactors
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PFR (Plug Flow Reactor)
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PFR (Plug Flow Reactor)
In a plug flow reactor the composition of the fluid varies from
point to point along a flow path; consequently, the material
balance for a reaction component must be made for a
differential element of volume dV.
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PFR (Plug Flow Reactor)
(1)
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PFR (Plug Flow Reactor)
dV =
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Advantages and Disadvantage of PFR
Advantages:
High Conversion per Unit Volume
Low operating cost
Continuous Operation
Good heat transfer
Disadvantage:
Undesired thermal gradients may exist.
Poor temperature control
Shutdown and cleaning may be expensive
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Comparison of PFR and CSTR
A larger volume is always required for the CSTR than for the PFR
in order to attain an equal specific conversion.
In the CSTR, the reactants in the feed are instantaneously diluted
to the concentrations in the reactor, whereas in the PFR there is
no mixing in the axial direction. Thus, the concentrations of the
reactants in the PFR are generally higher than those in the CSTR,
and reactions proceed under favorable conditions.
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Miscellaneous Bioreactors
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Bubble Column reactors
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Bubble Column reactors
Advantages:
BCs require very little maintenance
Less floor space
low operating costs
Disadvantages:
Short gas residence time
Less conversion as compared to other
reactors.
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Bubble Column reactors
Applications:
fermentation (production of ethanol and
mammalian cells).
biological waste water treatment (due to
aeration).
Production of a Single-Cell Protein from
Cheese Whey.
Absorption of oxygen/air in various aqueous
solutions.
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Air lift column bioreactor
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Air lift column bioreactor (common configurations)
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Air lift column bioreactor
All Air lift bioreactors, regardless of the basic configuration (external loop or
baffled vessel), consist of four main sections.
Riser: The gas is injected at the bottom of this section, and the flow of gas and
liquid is upward.
Downcomer: This section, which is parallel to the riser, is connected to the
riser at the bottom and at the top. The flow of gas and liquid is 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.
Base: In the vast majority of airlift designs, the bottom connection zone
between the riser and downcomer is very simple. It is usually believed that the
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.
Gas separator: This section at the top of the reactor connects the riser to the
downcomer, facilitating liquid recirculation and gas disengagement/ separation.
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Air lift column bioreactor construction
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http://image.slidesharecdn.com/airliftbioreactorppt-130111210405-phpapp02/95/airlift-bioreactor-ppt-8-638.jpg?cb=1357938893
Difference between bubble bioreactor and air lift column
bioreactor
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Air lift column bioreactor
Advantages:
Simple design
Highly energy efficient compared to CSTRs
Less floor space.
low operating cost.
Better heat transfer.
Easier sterilization (no agitator/moving part involved)
Disadvantages:
Higher gas throughput is required.
Higher pressure drop
Inefficient for the systems prone to foam formation.
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Air lift column bioreactor
Applications:
Air lift reactors are commonly employed
to shear sensitive cultures.
These devices are employed in large
scale manufacture of biopharmaceutical
proteins obtained from fragile animal
cells.
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Packed bed bioreactor
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Packed bed bioreactor construction
Shell (vertical or
horizontal)
Liquid distributor
Packing support
Packing hold down grid
Gas inlet
Gas outlet
Liquid inlet
Liquid outlet
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Packed bed bioreactor construction
Packing
Random packing
Structured packing
Random packing
Structured packing
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Packed bed bioreactor
Advantages:
Higher conversion per unit mass of catalyst than other
catalytic reactors
Low operating cost
Continuous operation
No moving parts to wear out
Catalyst stays in the reactor
Reaction mixture/catalyst separation is easy
Effective at high temperatures and pressures
Disadvantages:
Undesired heat gradients
Poor temperature control
Difficult to clean
Undesirable side reactions 41
Packed bed bioreactors
Applications:
Mainly used as enzyme immobilized
reactors
Bio catalytic reactions
Fermentation
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Fluidized bed bioreactors
Fluidization:
A process in which solid particles are set Fluid
Fluid
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Fluidized bed bioreactors, flow regime
Fluid velocity
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Fluidized bed bioreactor
Advantages:
Uniform Particle Mixing
Better temperature control
Continuous operation
Catalyst regeneration is easy
Effective at high temperatures and pressures
Disadvantages:
High pressure drop
Energy intensive operation
Particle entrainment
Erosion of Internal Components
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Packed bed bioreactors
Applications:
Mainly used as enzyme immobilized
reactors
To carry out bio catalytic reactions
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Difference between Fluidized bed bioreactors and
packed bed reactor
In fluidized bed reactor, large fluid-solid contact area is
possible and high rates of heat and mass transfer are
obtained.
Heat and mass transfer rates are usually higher in a fluidized
bed system as compared to a packed bed system.
Removal and addition of solid particles are easier therefore a
fluidized bed reactor is preferred over a packed bed reactor
where a catalyst requires frequent regeneration.
The catalyst particle may be reduced due to attrition. The flow
of solids and fluid are in cocurrent and therefore advantages
of countercurrent are not possible to obtain. Fine particles
may be conveyed which may result in the loss of solids and
there is a need for a separator downstream to recover the
solids.
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Photobioreactors
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Photobioreactors
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Photobioreactors
Advantages:
Cultivation of algae is in controlled circumstances, hence
potential for much higher productivity
Better control of gas transfer.
More uniform temperature.
Better protection from outside contamination.
Space saving – Can be mounted vertically, horizontally or at
an angle, indoors or outdoors.
Disadvantages:
Capital cost is very high.
The technical difficulty in sterilizing these photobioreactors
has hindered their application for algae culture for specific
end-products such as high value pharmaceutical products.
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Photobioreactors
Advantages:
Microalgae are a very diverse group of aquatic
microorganisms which could potentially be used for the
production of a wide variety of compounds.
Currently these reactors are used for the cultivation of micro-
algae and cynaobacteria which are further used to produce
important chemicals such as astaxanthin and β-carotene
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Heat Transfer
Introduction
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Introduction to heat transfer
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Introduction to heat transfer
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Introduction to heat transfer-2
Introduction to heat transfer
(Applications)
Car radiator
Cooling fins in an
electronic device
Boiler
Heat exchanger
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Figures http://www.lenntech.com/applications/process/boiler/boiler-feed-water.htm
Units of energy and heat transfer
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Modes of heat transfer
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Modes of heat transfer
http://www.beodom.com/en/education/entries/principles-of-thermal-insulation- 58
heat-transfer-via-conduction-convection-and-radiation
Conduction heat transfer
T1 T2
T1 > T2
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Left figure is taken from http://www.educationalelectronicsusa.com/p/heat-IV.htm
Convection heat transfer-1
Convection heat transfer
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Convection heat transfer-2
Convection heat transfer
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Types of Convective heat transfer
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Free convection heat heat
Types of Convective transfer
transfer
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ForcedTypes
convection heat
of Convective heattransfer
transfer
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Free and forced convection heat
Types of Convective heat transfer
transfer
In which of the following cases do you
expect greater rate of heat transfer?
1. Free convection
2. Forced convection
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Radiation heat transfer
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Individual and overall heat transfer coefficients
Outside film
resistance
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Individual and overall heat transfer coefficients
q
For inside film resistance: hi (T1 T2 )
A
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Individual and overall heat transfer coefficients
q U A dT
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Heat Transfer in bioreactor (Fermentor)
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Heat Transfer in bioreactor (Fermentor)
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Importance of heat transfer
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Downstream Processing
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Downstream Processing
Downstream processing means the recovery and purification of
bioproducts and the proper treatment and disposal of waste.
It is an essential step in the manufacture of bioproducts such as
antibiotics, hormones, vaccines, enzymes, natural fragrance and
flavor compounds etc.
Downstream processing is usually considered a specialized field in
biochemical engineering and chemical engineering.
Separation and purification of a desired product from the product
mixture e.g. fermentation broth or cell culture supernatant is a
crucial and challenging component of commercial biotechnology.
Product recovery usually accounts for a large portion of the product
cost and in some cases is the major manufacturing cost.
The ratio of fermentation to product recovery costs is about 60:40
for many antibiotics. For recombinant DNA fermentation products,
the cost of downstream purification is very important and can
amount to 80-90% of the total manufacturing costs.
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Downstream Processing
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Solid liquid Separation/ clarification
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Solid liquid Separation/ clarification
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Solid liquid Separation/ clarification
Sedimentation Tank
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Solid liquid Separation/ clarification
Gas 81
Solid liquid Separation/ clarification
The separation of solids from a liquid by means of porous medium or
screen which retains the solids and allows the liquid to pass is called
filtration. Very small items (such as bacteria) can also be separated
from fluids by filtration process.
Filtration is probably the most common means for separating solids.
Filtration offers many advantages for separating solids from liquids,
as it separates mainly on the basis of a single physical parameter-
the size of the solute.
Moreover, filtration can be very cost effective; compared to
centrifugation it consumes less energy and requires considerably
less capital investment.
Versatility is another advantage.
Separation of insoluble membranes exclude solutes as small as 10
o
A or so in diameter, whereas other membranes allow passage of
particles in the hundred-micron (million-A) size range.
In addition, many different biocompatible filter materials are 82
available.
Solid liquid Separation/ clarification
Permeate Permeate
Flux
Cake thickness
Cake thickness
Flux
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Solid liquid Separation/ clarification
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Classification of Filtration process
Filtration Driving
Pore size Application
process force, ΔP
Removal of suspended particles,
concentration of insoluble material, cells
Microfiltration 0-1 bar 0.02-10 μm
from fermentation broth, clarification of
disrupted cell slurries
10-3 -10-2 μm
Reverse 30-100
Removal of salts from water
osmosis bar
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Filtration Equipment
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Filtration Equipment
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Filtration Equipment
Filter Press
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Filtration Equipment
Filter Press
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Cell Disruption
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Cell Disruption
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Cell Disruption: summary
To release maximum amount of the product in an active state.
Factors to consider: inactivating effects such as shear, temperature
and choice of disruption methods.
Mechanical disruption is the most common means to release
intracellular products in laboratory and in industry.
Ultrasonication is common in the lab-scale but the removal of heat
is difficult on a larger scale.
Two common mechanical cell disruption industrial processes are
1. High pressure homogenization: the cell suspension is forced at
high pressure through an orifice to emerge at atmospheric
pressure. The sudden release of pressure creates high shear.
2. Vigorous agitation with abrasives: agitation with glass in bead
mills ruptures the cells by high shear and impact with the cells.
(Size of beads: 0.2-0.5 mm for bacteria; 0.4-0.7 mm for yeasts.)
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Cell Disruption: summary
Two common non-mechanical cell disruption industrial processes are
1. freeze/thaw: freeze at -80 oC and rapid thaw at 37 oC; disrupt the
cells by causing changes in the structure of the cell wall and
membrane.
2. Organic solvents and detergents: extract cells which are more
permeable and soluble.
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Concentration of biological product
After initial separation, the filtrate contains 85-90% of solvent (mostly
water). Removal of solvent can be done in different ways, for example
Distillation
Evaporation
Extraction
Precipitation
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Concentration of biological product: Distillation
Distillation is one of the most important processes for separating the
components of a solution. The solution is heated to form a vapor of the
more volatile components in the system, and the vapor is then cooled,
condensed, and collected as drops of liquid. By repeating vaporization
and condensation, individual components in the solution can be
recovered in a pure state.
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Concentration of biological product: Evaporation
Works by evaporating the solvents using heat. It is simple but energy-
consuming, normally using steam as the heat source in a large scale.
Applicable for food and other stable biologics, but seldom suitable for
processing of biologically active proteins.
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Concentration of biological product: Evaporation
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Concentration of biological product: Extraction
Extraction is a process in which two phases come into contact with an
objective of transferring a solute or particle from one phase to the other.
If two phases are poorly miscible liquids, the technique is called liquid-
liquid extraction (or solvent extraction). Liquid-liquid extraction is
commonly used for the separation and purification of biological
products.
Efficiency of the process depends on the distribution of substances
between two phases.
Distribution Partition Coefficient:
In an extraction process, the compounds are separated due to their
different partitioning between two phases that is a result of the difference
in their relative solubilities in two liquid phases. Distribution of a solute
between the two phases is usually expressed in terms of partition
coefficient.
Ciextract
K
Ciraffinate 100
Concentration of biological product: Extraction
Types of Extraction employed in industry
Organic solvent extraction: Small lipophilic molecules can be
extracted by organic solvents.
Physical extraction: distribution is based on the physical preference.
This applies to nonionizing compounds and the extraction is optimized
by screening for the solvents that have a high K value.
Dissociative extraction: distribution is based on the difference in the
dissociation constant of the ionizable components, e.g. extraction of
penicillin.
Aqueous two-phase extraction: Solvents used for extraction are
water soluble and mostly used for extraction of protein etc.
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Concentration of biological product: Extraction
Example: Extraction of proteins using Aqueous two-phase systems
(ATPS)
Some water based polymer solutions are immiscible with each other or
with salt solution of high ionic strength and are capable of forming two
two phases on mixing.
For industrial processes, polyethylene glycol (PEG)/salt and Dextran
system is often used for their low cost to extract valuable proteins, from
cellular debris etc.
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Concentration of biological product: Extraction
Example: Extraction of proteins using Aqueous two-phase systems
(ATPS)
Some water based polymer solutions are immiscible with each other
or with salt solution of high ionic strength and are capable of forming
two phases on mixing.
For industrial processes, polyethylene glycol (PEG)/salt and Dextran
system is often used for their low cost to extract valuable proteins,
from cellular debris etc.
Partitioning of a component is based on its surface characteristics,
nature of phase components and the ionic composition.
Phase separation is slow (from minutes to hours) but can be
speeded up by centrifugation.
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Concentration of biological product: Extraction
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Concentration of biological product: precipitation
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Purification of biological product: Chromatography
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Chromatography
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Chromatography: working principle
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Chromatography
Various types are available:
Size Exclusion Chromatography
Ion Exchange Chromatography
Reverse phase Chromatography
Gel permeation Chromatography
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Chromatography
Gas Chromatography
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Image taken from https://en.wikipedia.org/wiki/Gas_chromatography
Chromatography
Chromatogram
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Image taken from http://www.4college.co.uk/a/Cd/Glc.php
Chromatography
Liquid Chromatography
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Image taken from https://en.wikipedia.org/wiki/Gas_chromatography
Chromatography
Liquid Chromatography
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Image taken from https://en.wikipedia.org/wiki/Gas_chromatography
Formulation of bioproduct
Freeze Drying
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Formulation of bioproduct: Freeze drying
Advantages:
It has many advantages compared to other drying and preserving
techniques.
Freeze Drying maintains food/ biochemical and chemical reagent
quality because they remains at a temperature that is below the
freezing-point during the process of sublimation.
The use of Freeze Drying is particularly important when processing
lactic bacteria, because these products are easily affected by heat.
Food/biochemicals and chemical reagents which are Freeze Dryed can
usually be stored without refrigeration, which results in a significant
reduction of storage and transportation costs.
Freeze Drying greatly reduces weight, and this makes the products
easier to transport. For example, many foods contain as much as 90%
water. These foods are 10 times lighter after Freeze Drying.
Disadvantages:
Long processing time is required.
Capital cost is more as compared to other dryers.
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Formulation of bioproduct: Spray Drying
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Formulation of bioproduct
Spray Drying
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Downstream Processing Summary
Downstream processing consists of most important steps
in recovery of valuable of product.
Major steps include
Solid liquid separation/ clarification
Cell Disruption
Concentration/Purification
Formulation
It helps to enhance the shelf life of final product.
It accounts for the major cost of final product.
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