Downstream Processing - Biotechnology Engineering Video Lecture - Biotechnology Engineering (BT)

[Music]
welcome to the course on bioprocess in
the downstream processing for the next
40 lectures I'm going to talk about the
various unit operations involved in
downstream processing how do you go
about designing a downstream processing
equipment what are the advantages
disadvantages of various downstream
processing equipments downstream
processing becomes very relevant in the
area of bio process as well as in
chemical process technology downstream
processing has been there for a very
long period of time especially in the
area of chemical engineering where
chemical engineers used to practice
recovery of products using filtration
distillation separations rolling
extractions and and so on but in the
area of bioprocess technology as your
handling of enzymes or proteins or
biomolecules the complications are
slightly much more and also you need to
consider the stability of these
biomolecules so new techniques also came
into being techniques like
chromatography and techniques like
membrane separations have been
incorporated in Indy bioprocess
technology also actually so what does
downstream processing means it refers to
recovery purification of biosynthetic
products products coming out of a
biological operation it could be a
pharmaceutical product it could be
related to food or nutraceuticals
it could be related to chemicals it
could be a bulk chemical or a specialty
chemical it could be products related to
healthcare or medical biotechnology so
you try to recover after you manufacture
using an animal or a plant tissue or a
fermentation broth so what's the role of
a downstream processing
it's meant to separation it's meant for
purification of a bio product from
unwanted metabolites so once you carry
out a fermentation or once you carry out
a bio transformation you're going to
have the desired product as well as
undesired waste product side products
and so many wasteful dead biomass and so
on so the idea is to recover and isolate
the product of your interest from a
large combination of unwanted products
so that is where the downstream
processing comes and that becomes a big
challenge because you would like to
recover your products in a very
economical way and try to recover it as
much as possible that means and not lose
anything in the waste but try to recover
as much as possible into your final
purification that's the main challenge
of further downstream processing
actually so let's look at a flow sheet
the alcohol fermentation I mean it's
been there for almost a 5,000 years the
fermenting from sugars fermenting from
fruits converting into alcohol and once
they convert into alcohol it contains a
large amount of liquid where your
alcohol the percentage of alcohol is
very very little so the idea is to
recover as much of possible the alcohol
from this large quantity of liquid and
then concentrate it to high degree of
purity so that's what is alcohol
fermentation is all about so if you look
at the entire flow sheet of alcohol
manufacturing you have the fermentation
taking place here that is where the
sugars are getting converted into the
fermenter alcohol but if you look at the
right-hand side in this flow sheet the
entire portion is the called the
downstream processing this is where you
are trying to isolate your alcohol and
then you are trying to purify your
alcohol to a very large and concentrated
liquid form so you can see you have just
one fermenter here but you are going to
have your very very large number of unit
operations on the right hand side which
help you to isolate your product as well
as they purify the product and you just
look at these various unit operations
that is called you know you have a
vessel to hold your fermentation broth
so the alcohol concentration may be very
little 8% 9% that's all but ultimately
you would like to get almost plur 90%
pure alcohol so once you collect the
fermentation broth and you may be doing
a distillation because alcohol boils at
lower temperature than rest of the mass
so the distillation happens here and
then the product that's coming out is
condensed here this will be mostly
alcohol and of course you are going to
have some water and if there are any
other side products and which are also
going to be of lower boiling point is
going to also get condensed here now the
bottoms you filter and then you collect
the solids you dry the solids finally
you may get some dried grainy material
you may also get dried soluble material
so this can be used as animal feed it
may it may be rich in protein it may be
very useful for the animal field so once
the alcohol is distilled out which
contains water and other low boilers
it's further distill here these are
called a purification and rectification
columns and finally you get very very
pure alcohol on the extreme right hand
side and you are going to have a lot of
water coming out as the bottoms here so
this particular operation of
purification of alcohol from
fermentation contains several
distillation columns and then filters
and dryers so the downstream in alcohol
fermentation are made up of filters the
dryers and the distillation column quite
a simple downstream operation if you
consider alcohol fermentation but if you
go for other chemicals like bulk
chemicals or even speciality chemicals
even
products related to drugs or
pharmaceutical you may have very
stringent requirement for purity because
your pharmaceutical product has to be
extremely pure so you may go into more
purification steps so you may go into
steps like chromatography different
types of chromatography you may go into
separations like membranes and so on
actually because here it's your product
which can take which can withstand large
high temperatures you are resorting to
distillation but if you are going to
have products which are like a protein
or which are enzymes which might not be
able to withstand the temperature you
may not be able to use this relation
there you may have to use some other
downstream process so depending upon the
type of product which you are trying to
recover the nature of the downstream
varies quite a lot actually so a very
simple fermentation of sugar converting
into alcohol requires several downstream
and as I said mostly distillation
columns filters and dryers and then we
will be seeing more of these and you'll
also see how you go about designing
these various minute operations and what
are the principles involved in these
unit operations that's what we are going
to look at in the next course of time
actually so and a downstream can help in
manufacture of pharmaceutical products
all the antibiotics are made using in
fermentation or biotechnology routes and
so they resort to quite a lot of
downstream steps you can use it for
making hormones it could be human growth
hormone or insulin it's used in anti
body manufacture vaccine manufacturers
in enzymes which are used in diagnostic
kits enzymes used in industrial
applications even you are a soap for
example contains enzyme and can be used
for natural fragrance flavors food
products and so on so almost all
biologically manufactured products
required downstream steps hence
downstream becomes extremely important
so downstream can be used once you
ferment a particular material using a
microorganism or a mammalian or insect
cell culture and major product is
protein but then nowadays even bulk
chemicals are being manufactured using
biological approaches because the
techniques have become so cheap that
they are becoming very competitive when
you compare it with chemical
manufacturing itself okay so what
happens after the fermentation or
biotransformation the desired product is
either inside the cells that means
microorganism or it is in the medium or
in the broth okay so your product may be
inside your microorganism bacteria or
fungus or it might be in the medium or
in the broth and generally the
concentration is very very low five to
twenty five percent so your idea is to
recover concentrate purify to almost 100
percent so if it's a drug it has to be
extremely pure the impurity levels have
to be and practically zero percent if it
is a bulk chemical then the impurity can
be even 5 percent or 10 percent so
depending upon the type of application
the purity levels are decided upon
action okay if you look at typically a
your bioprocess product manufacturing
and this is called a flow sheet of
manufacturing process so most of the
biochemical processes will have these
various units this is the heart of air
by a process manufacturing plant this is
called a reactor it could be called
fermenter if you are fermenting your
sugars into the desired product it could
be called a reactor if you are using bio
transformation or enzyme catalyzed
reaction so depending upon the type of
process you are doing it may be
all the fermentor or a reactor here this
is the heart of the entire bio process
the the right hand side we call it as
the downstream and the left hand side is
called the upstream this is where you
are preparing your medium preparing your
micro organism and then you feed it into
the reactor here you are recovering your
product that means you are isolating
your product you're purifying your
product and making it 100 as pure as
possible so during the purification you
are going to get side products unwanted
products you are going to get a lot of
waste material which all goes to waste
treatment plant so after the
fermentation you may recover the bio
catalyst if it's an enzyme you would
like to recover the enzyme and put it
back inside your for inside your reactor
because enzymes are very expensive so
you don't want to throw the enzymes out
so you try to recover the enzyme and put
it back into the reactor if you have
yeah unconverted raw materials you again
like to recover and put it back suppose
you have glucose and converted glucose
you try to recover the glucose and put
it back because cost can be reduced the
manufacturing cost can be reduced by
doing this type of recycling this is
called recycling
once you have recycled your raw
materials and you are catalysts you have
your product very dilute product 5% 10%
of product so you are recovering your
product here and then finally you are
purifying a product okay and then
unwanted material goes into waste
treatment unwanted material means it
could be dead biomass it could be cell
debris it could be waste material salts
it could be broth and so on actually so
they all go into the waste treatment
plant before they are completely
disposed into the effluent treatment
facility actually so a typical
manufacturing plant a bio process
manufacturing plant will be looking like
this and we our focus is more on this
right-hand side of it this is what is
called
downstream and this is what we are going
to talk about them in the course of our
lectures so now what is raw material
preparation that's the left-hand side
which we saw we are preparing the growth
medium growth media means it may have a
carbon source nitrogen source minerals
micronutrients oils everything which are
needed for your and growth of the
microorganism if it's then you need to
sterilize all the growth media because
whatever you feed in to your fermenter
has to be completely sterilized so this
is what is called a raw material
preparation section then you have a
section for preparing your microorganism
or the enzyme that's the bio catalyst
preparation section so if you are
preparing microorganism you need to have
a inoculum medium inoculum preparation
section you need to have the
microorganism at the correct stage of
growth and then you need to sterilize
the bio catalyst so that both the raw
materials and the enzymes or
microorganisms are fed into the
fermenter that's the upstream section
okay your product could be either inside
the microorganism inside a bacteria or
fungus or it could be in the medium that
means if it is inside outside the
microorganism that's called
extracellular if it's inside the
microorganism that's called
intracellular and so if the product is
in the extracellular life becomes very
easy so all you have to do is you have
to remove the the bacteria your product
is here but then if it is inside then
it's much more troublesome you have to
first recover all the microorganism or
cells and then you have to break the
cells and then extract your product so
the number of unit operations number of
process steps are more that means you
are going to take more time doing it
that means cost also increases so
extracellular product is always desired
because your product is in the medium so
you just have to filter
take your cells and throw them out and
you have your product in the liquid
medium so in intracellular you have to
recover your cells break the cells and
then get your product out of the cells
okay so the number of steps are more
cost is also more there are many
products which are made intracellular
many products which are made
extracellular some proteins are
intracellular that means they grow
inside has a Golgi body or they are
inside and so you need to take it out
that means you need to break the cells
and take the product out if it's a
liquid product you are interested in
then they are extracellular and that
then you can take the liquid medium and
then recover your product so ideally you
would like to have extracellular product
rather than intracellular product
because as I said the number of steps
involved are much more in intracellular
and the number of steps involved in
extracellular are less okay if you look
at down downstream processing it's an
interdisciplinary area you need the
expertise of biochemical engineers you
need the expertise of chemical engineers
also because there are several
operations which are very chemical
engineering oriented you need the
support from chemists we need support
from biochemist biologists analytical
chemist so all these people have to put
in their expertise and knowledge if you
want to make a good downstream process
so it's extremely interdisciplinary and
it's a multidisciplinary task so it not
only involves separation purification
but you are also increasing the
concentration of your desired product
like I talked about alcohol fermentation
after the fermentation from the
fermenter the amount of alcohol or
ethanol in the broth may be 8% 9% but
finally you want to make your
concentration to almost 90 percent so
you are not only purifying your product
you are increasing it to very large
concentration
so what are the different steps in the
downstream process it may have
separation of cells or you sometimes
call it biomass because it's a
biological mass as the cells grow they
form and large amount of mass then if
it's an intracellular as I said your
product is inside the cells then you
need to break the cells that's called
the disintegration of the cells okay so
you need to break the cells if it is an
extracellular process or product you
don't need this particular step you can
jump from here to here then you need to
separate your product you need to
concentrate your product then you need
to purify a product so this number of
steps depending upon it depends upon the
type of product if it's a pharmaceutical
product the product has to be very very
pure so you need to keep on purifying it
to almost hundred percent and but if it
is a bulk chemical you don't need to do
too much purification so you can start
from separation concentration little bit
of purification if it's an animal feed
again it may be lying between too much
purity and too little purity so
depending upon the type of product the
purification steps vary so for each one
of them you may have several unit
operations and by the time you get a
product of extremely high purity you may
have several and unit operations done
and finally if it's a solid material you
would like to dry the product so that
all the moisture is removed because the
moisture leads to sometimes instability
in the product especially enzymes lose
their activity over a period of time and
in there is moisture and that's called
shelf-life so if you keep your enzyme
with moisture and over a period of time
ends I may lose activity so the best
thing is to dry it up so when you dry
even solid material loses its volume so
storage becomes much easy transportation
becomes much more easier so the cost of
transportation also goes down so drying
is usually resorted to if you are
interested in a solid product if it's
not a solid product then of course if
it's a liquid product you don't need to
dry the
final product so you may stop with here
so generally solid material is you is
done with trying so as I said there are
the common stages in downstream so you
are separating the cells you are
separating the cell debris because the
broken cells are called cell debris is
then other particulate matter foreign
fermentation especially you had a lot of
salts in the fermentation broth so the
salts start precipitating out so that's
called and then they start agglomerating
that's called a particulate matter so
all these have to be removed that's the
very first step in downstream and that's
called the removal of insolubles then
the next step will be product isolation
the product concentration will be very
very small 7% 8% so you need to take out
the product from this large amount of
liquid so you may like to remove water
what it is present because most of the
fermentation is done in a quest so there
is plenty of water you are adding soils
so you need water again to dissolve the
salt so there are there is plenty of
water in your fermentation broth so
removal of water
there are several impurities present so
you are removing the impurities as well
let's call the product isolation the
next step is product purification that
means you are trying to purify the
product so by the end of product
isolation your product may be 30 40 50
percent pure okay but then you if you
want to achieve 90% pure 95 percent pure
then you need to resort to this product
purification you are removing the
contaminants and there could be side
products which may be contaminants
there could be unwanted reactions which
may be reactants which may be
contaminants so you need to remove all
these and then you need to bring in the
where the physical and chemical
properties of those contain contaminants
and finally your doing the product
polishing that means you are stabilized
stabilizing the product for transport
convenience and shelf-life let's call
the product polishing you may add
certain antioxidants to decrease
the oxidation of your desired product
over a period of time you may add other
stabilizers so that your product doesn't
degrade over a period of time you may
add stabilizers so that the pH and
doesn't vary when you keep it in the
shelf over a long period of time so like
that
you will be adding several stabilizers
and so that the product shelf life is
improved and the product transportation
is also improved so these are the common
stages in your downstream processing
removal of insolubles that means you are
removing the solids from the liquid then
the product isolation that means you are
isolating your product from a very very
large quantity of liquid material
concentrating at up to fifty sixty
percent then purifying the product
almost 90 percent pure or even
ninety-nine if it's a pharmaceutical
product and finally you are adding some
stabilizers to your product so that you
improve this shelf life of the product
for a very very long period of time so
these are the various steps in the
downstream one hazard actually okay so
how do you remove insoluble
that means you are removing solid
material from liquid so there could be
many many techniques we will spend time
in the next course of the various
lectures solids can be removed by
filtration they can be removed by
centrifugation they can be removed by
membrane type of micro filtration nano
filtration membrane filtration and so on
so all these techniques are meant to
remove solid from the liquid next is
isolation of the product and it can
involve cell disruption that means if
your product is inside the cell you are
breaking the cells
that's called cell disruption the cell
disruption can be a mechanical type of
process it could be your enzymatic
process it could be a thermal process so
again we will spend their time in the
next course of
on this particular aspect cell
disruption and then you are extracting
your product using a solvent and you may
be able use adsorption type of technique
to remove your product or you may use
ultra filtration technique or you may
use a precipitation type of technique
all these techniques are meant for
isolation of your product the next step
is once you have isolated the product
you are purifying your product this
involves chromatography different types
of chromatography affinity
chromatography size-exclusion
chromatography reverse phase
chromatography so you see where
purification is always achieved by
chromatography and chromatography is a
very expensive technique and so it adds
to the cost of your final product and
the chromatography really purifies your
product from maybe 60% to more than 90%
and finally you are polishing your
product that means if it's a solid
material you can get the product in a
crystal form that means a very pure
product can be crystallized and you can
end up with a crystallized product you
can reduce remove the water content by
life--all ization or you can even use
this equation or it can even you do
spray drying like your coffee powder is
a spray dried product the
crystallization even enzymes could be
crystallized so by advantages of
crystallization is by crystallizing your
enzyme you are removing all the water
present in the enzyme so the shelf-life
of the enzyme or the activity of the
enzyme is retained over a very very long
period of time so you you resort to the
various techniques he mentioned in this
slide for achieving your desired product
and desired concentration and desired
physical chemical properties so if it's
a solid you bring it into your solid
form if it's a liquid you maintain it as
a liquid form and you try to stabilize
it so that it doesn't lose its activity
during a transportation as well as when
you keep it in the shelf
okay so this is a nice slide which sort
of separates the intracellular product
that means products inside the cell and
the extra syllable products that means
when the product is in the media that's
they are outside the cells so when you
have intracellular product of course you
have to disrupt yourself that means you
have to break the cells to get your
product out but if you are having
interest in the product you are not
interested in the biomass or the
microorganism you can throw the
microorganism out so you use a
filtration technique you can use a
centrifugation techniques or even
sedimentation sedimentation is nothing
but settling technique so if the solids
are very heavy they settle down so the
liquid on the top rises and you can take
your liquid because your product is in
the liquid flocculation techniques if
your solid is not settling down that
means it's not very heavy and the solid
is floating on top of your liquid you
can collect the solid by flocculation
and remove the top portion so the
remaining liquid will be containing your
desired product so two major areas one
is the intracellular products and the
other is the extracellular product so
both has different types of techniques
once you have disrupted your cell the
methods could be either mechanical based
methods or it could be non mechanical
based methods the mechanical based
methods and contains homogenizers
ultrasonic heaters or ball mills or non
mechanical method could be an enzyme you
can use an enzyme to break the cells or
you can use a chemical to break the
cells or you can use an osmotic shock to
break the cell so by breaking the cells
you are releasing your product that is
trapped inside the cells to outside once
you have done that you can go to the
right hand side for the product
isolation and the product purification
so product isolation will contain things
like precipitations extractions so the
precipitation may contain them using a
salt using organic solvent extraction
can be used you can use a solvent like a
sit down or a chloroform or ethyl
acetate or you can use him in water or
you can use even think techniques like
supercritical type of extraction here so
this is the product isolation side of it
and then the purification part of it is
using different types of chromatography
like I mentioned before the affinity
chromatography the ion exchange
chromatography reverse phase or gas
chromatography or even liquid phase
chromatography can be resorted to and
you can purify your product actually so
intracellular requires cell disruption
and once you have disrupted the cell you
can go to the side of it and then use
the recovery of product recovery
techniques and product purifying
techniques so if you are talking about
recovery whether it's a protein or
whether it is a metabolite so you are
talking about cell separation that means
you collect your cells first and if your
cell is your contains your desired
product you sell is disrupted using
various techniques I talked about
homogenizer and bead milling chemical
techniques and somatic techniques lysing
techniques and then once you have broken
the cells and extracted the product from
the cells you can remove that cell
debris so that means the broken cells
using the centrifugation membrane
process to face aqueous partitioning
technique and so on and then finally you
are concentrating your product using
different types of precipitations and
filtrations and then you go into protein
purification using an exchange methods
chromatography techniques and then
finally the polishing method where you
are using crystallizes life lasers are
drying methodology if it's a metabolite
instead of a protein then you can use
even distillation type of techniques
because a prior-year metabolites or
organic chemical can withstand a higher
temperature and like a protein protein
will not be able to withstand very high
temperature so most
the protein separation techniques will
involve extraction or involve potential
whereas if it's a metabolite we can use
distillation type of method and
distillation is a very simple method and
it produces very pure product depending
upon its vapor pressure or depending
upon its boiling point with respect to
rest of the material so distillation is
a very easy technique to resort to if
the material can withstand very high
temperature and then later on whether
it's a protein or whether it is a
metabolite you may resort to
crystallization or you may resort to
spray drying or life--all ization
depending upon the nature of the product
of the desired product just like
downstream processing we also have
techniques called analytical bio
separation okay so in analytical bio
separation that's like downstream
processing you are purifying a product
you are separating a product you are
purifying a biological product that
means a biological product could involve
a DNA or it could be involving a protein
or it could involve amino acid and so on
but only difference between downstream
processing an analytical balance
separation is the scale of operation in
a downstream processing and you are
manufacturing and purifying a product in
a very very large scale it is meant for
manufacturing and marketing
whereas in analytical bio separation you
are purifying a product a component from
a mixture of components where the
quantity may be very very small it is
meant for analytical use you want you
are interested in a particular
biomolecule you want to study the
characteristics of the biomolecule in a
very large small scale in your lab so
the quantities are very very small
unlike and downstream processing so in a
downstream processing and you are
manufacturing a product so the scale of
operation is very very large but as an
analytical bio separation you use
similar separating techniques but the
idea is you are isolating a small
product from a very low
quantity of material and you are going
to study its properties in the lab you
are going to do certain experiments with
that particular biomolecule so the scale
of operation is very different that's
the difference between an analytical bio
separation and a downstream processing
okay let's look at the the various
issues that are involved in downstream
unit operation now let's consider
imagine you have a reaction taking place
in a reactor it could be a bioreactor it
could be a fermenter right and then you
are doing a separation some type of
separation any type of separation you
are resorting to and you are getting
some product out here imagine the reeled
of the reaction is 95 percent that means
0.95 and the efficiency of the
separation is 0.98 that means efficiency
of the separation process is 98 percent
so the overall product yield you are
going to get is the multiplication of
this number with this number so when you
multiply these two numbers you are
getting 93 percent that means you are
losing the product seven percent of the
product when you move from here to here
some product is lost here and some
product is lost here during this two
steps now let us go further imagine I
have a fermenter or a bioreactor here
and I am using three different
separation steps I am doing some
separation in separator 1 then I am
doing some other separation in separator
2 and then another separation in
separation 3 and each one of these
separators have has here a certain
efficiency it cannot be a hundred
percent it can be 98 95 90 and so on it
will never be 100% efficient so you are
always going to have some little bit of
loss if the yield in the reactor is 95
percent and efficiency of separation in
each of these separator is 0.98 0.98
point nine eight
so overall product
yield if I do I multiply all these
numbers I multiply 0.95 and then I'm
multiplying 0.98 9 8 9 8 so if I
multiply all these terms together I get
0.894 that means about eighty nine point
five four percent so about ten percent
of the product is lost when I move from
here to here did you notice that so when
I have three separators and one reactor
each one has certain either yield or
efficiency
although each of the separator
efficiency is 98% and the yield in the
reactor is 95 percent when I multiply
all of them I end up only with the
eighty-nine percent that means I am
losing ten percent product as I move
from here to here
let's slightly make it more complicated
I have one reactor I have one separator
I have another reactor I have another
separator then I have third reactor and
third separator and the yield in each
reactor is 95% and yield in each
separate separator that means efficiency
in each separator is 98% so if I want to
calculate the overall efficiency of the
entire Train of reactor separator I will
just multiply 0.95 three times 0.98
three times so what do I get I get
overall efficiency has eighty percent
that means I am losing about 20 percent
of the product when I move from here to
here so just by putting three reactors
and three separators and although the
efficiency in each separated is very
high point nine now you need an eel in
the each reactor is very high point nine
five I am losing twenty percent of the
product that means
my overall production yield is only
eighty percent if I keep reducing this
lost I'll be able to increase this
particular term that means I will be
able to manufacture more of the desired
that means which adds to the overall
sales so this is a very very important
concept one needs to understand that
efficiency in each separation of an
operation has to be extremely high and
yield in each reactor has to be
extremely high even if they are very
very high if you have a train of
separators if you multiply the
efficiency in each of the separator you
may end up having a overall yield for
the entire train to be much less which
you could not have imagined and that
means the amount of product loss could
be pretty high although when I look at
each of the separator I may think each
of the separator is performing extremely
well because each of the separator has
98% separation efficiency each of the
reactor has 95 percent yield but when I
multiply all of them I will end up only
with 80 percent and which leads to 20
percent loss of the overall product when
I move from this place to this place so
the efficiency of the entire process
flow sheet is only 80 percent that means
we are losing a lot of material and
which is lost which cannot be
manufactured and sold so one needs to
consider when one is designing and
downstream operation that efficiency of
the downstream operation has to be as
high as possible and if it is lower it's
going to add up to several lower
downstream unit operations and the
overall down
efficiency of the entire process could
be extremely low there are various
aspects one needs to consider while
redesigning downstream process okay the
very first thing is what is the cost of
the equipments which we are we planned
to purchase I am if I am purchasing a
filter how expensive it is if I am
purchasing a centrifuge how expensive it
is because that is going to add to the
capital cost of
the equipment should I buy a centrifuge
or should I buy a filter can I do the
same job using a centrifuge which I can
do with the filter and if the filter is
cheaper than a centrifuge then isn't it
better to go for a filter rather than a
centrifuge so one needs to consider
various options with respect the cost so
that the overall cost of the plant is
low the next step is cost of operation
how much water I am going to use how
much steam I am going to use what are
the various solvents I am going to use
because each of them cost money in
running the plant each of them come add
to the operating cost or manufacturing
cost of my product so higher the
manufacturing cost higher is the selling
price of my final product so I would
like to keep the use of the steam use of
water use of solvent use of other
utilities as much as low as possible so
that the overall operating cost is low
next is safety the unit's I am designing
do they have inherently safe operating
conditions or they are going to be
unsafe am I using toxic chemicals am I
using hazardous chemicals are the
conditions I am using like the
temperature pressure and are they safe
conditions or are they unsafe conditions
I mean exposing my people to these
chemicals and solvents all these aspects
needs to be considered when you are
designing a downstream equipment and
they all come under the aspect of safety
the next one is something called the
green chemical chemistry approach can I
combine two or three downstream into
single one so that I don't have to
perform some downstream then go to
another vessel perform another
downstream can I do two things at the
same time that's called telescoping can
use less solvents can I use less
chemicals so that I can use
I can produce less waste so that the
environment is not affected can i
generate less space can you do things at
milder condition do I have to use very
high pressure or I can do at very very
low pressure sim or ambient conditions
ambient temperature so all these aspects
needs to be considered when I am
designing a downstream equipment because
they all add up to a very safe and green
chemistry based downstream reactor the
operation design and to continue Phi the
further what type of waste I am
producing after I do the downstream
purification or downstream isolation
when I am a isolating a product whatever
is left behind is a waste does the base
contain solid as the waste contain
liquid is the waste toxic can it just
dispose it in the environment or do I
need to do any treatment does the waste
produce gases all these aspects needs to
be considered so when I am talking about
waste it is solid its liquid its gas all
these three needs to be thought of
I mean producing toxic obnoxious gases
during my downstream operations so these
environmental issues needs to be
considered when you are designing a
downstream next is scalar when we
develop a downstream process in the lab
we are doing it in at hundred milliliter
scale but when we go for a manufacturing
facility we are talking about in terms
of thousand ten thousand liter scale so
that's a big large increase in volume
will I be able to carry out the same
efficient process as I did in my lab at
100 milliliter scale so that's called
the scale-up moving from bench to
full-scale commercial production so when
you move from lab to large-scale
thousand or ten thousand liter scale do
things happen the same way as happy
in a small scale so you need to consider
those aspects as well
finally the utilities what type of
utilities are required for performing
these operations do I require steam do I
require hot oil do I require hot water
chilled water coolant they require
nitrogen gas or oxygen gas and so all
these needs to be considered so if I am
cooling something I will require cold
water or chilled water if I am heating
something I you require steam if I heat
at very high temperature I will require
hot oil
if I want inert condition I will require
nitrogen or carbon dioxide if I want to
do a oxidation I will require oxygen so
you need to depending upon the type of
down stream you are doing you need to
decide what type of utilities are
required and utilities add to the
overall operating cost so how
efficiently can I do and so that my
overall operating cost is always low so
you need to consider and from that angle
as well the use of utilities minimize
the use of utilities so that your
operating cost is less so all these
aspects needs to be considered when you
are doing a design of a downstream unit
so I talked about scale-up
when we move from your lab scale which
is say about 100 milliliter scale when
you move to a thousand or 10,000 liters
scale that manufacturing stage yeah it
doesn't happen in one go you need to
consider several aspects when you are
doing a scalar so this particular slide
shows you what are the various steps
involved in scale-up so this is your
first step this is the lab scale process
you are developing a process in the
laboratory scale the overall quantity
may be only 100ml you are up you are
modifying conditions checking on pH
checking on temperature checking on
carbon source nitrogen source checking
on quantity of various fluids so that
you get a very optimum process in the
lab scale okay then you move to pilot
scale so from milliliter scale you don't
directly go to thousand or 10,000 liter
you may go to ten liters or 100 litres
scale so that's called a pilot scale so
at that time you will require a lot of
data you will require physical chemical
properties you will require density of
the fluids will require surface tension
boiling point
vaporizing point all these physical
chemical properties for various fluids
you are using or required so you may be
collecting it from literature or you may
be doing collecting it from your own lab
because if you want to design something
you need all the physical chemical data
here once you have done that you need to
look at the cost how costly it is is it
okay can I do this whole job is it
economical or should I follow some other
technique so this is where you do a
costing here and once you had done a
costing you know how expensive is this
particular step then you identify other
issues there could be several other
issues which I talked about there could
be safety issues there could be a very
large increase in cost issues there
could be green chemistry issues and so
on actually so if you are not very happy
with that you may think about
alternative approaches that means how
can I perform this aspect using some
other techniques some other downstream
purification techniques so that is the
time you say should I accept or reject
if I accept I may go further and do
further scale-up go to the manufacturing
plant and do it in a very large scale
but if I decide to reject what do I do
I then think about some other operation
so initially I made a thought of doing
these purification using distillation
but I am not very happy because of
safety so I may go and think of
filtration or membrane type of
filtration
I might have initially thought of
centrifugation I find the centrifugation
is not very good so I may go into
membrane filtration so you may change
from one down stream to another down
stream because the cost may be very high
or the safety issues may be
problematic or you may be using unwanted
toxic chemicals waste issues may be too
much for you to handle so you may go
into some other type of fun downstream
process approach a tree so these are the
various steps in scale up when you move
from the lab scale right up to the
manufacturing scale so it is almost like
a an iterative process and sometimes you
may go all this way you might have spent
about six to 12 months and you find out
there are issues and you may come back
again and start all over again so
sometimes you may lose out time because
of this particular aspect of accept of
or reject okay and let's look at
something called the most important
thing that's called the mass balance
imagine your unit it may have two inputs
liquid is coming in at certain volume
and at certain concentration of that
product okay and two liquids are going
out at certain volume add and some other
concentration so this is liquid one
coming in at volume flow rate one the
volumetric flow rate could be say liters
per hour or a meter cube per hour and so
on similarly the concentration could be
gram mole per liter or grams per liter
micro micro micro moles per liter and so
on actually then another liquid may be
coming at some other flow rate some
other concentration two streams may be
going out at some other flow rate and
some other concentration I'm just
showing two input and two output you can
have multiple inputs and multiple
outputs okay depending upon the type of
downstream for example you may be having
a extraction in extraction you have your
liquid you are adding a solvent so you
have to look at its input and then you
are extracting using a solvent so your
product may be in the solvent so that
could be you
liquid and the other one could be the
bottoms so this is a typical extraction
type of unit so if you want to look at
the mass balance at steady-state
whatever comes in has to go at
steady-state okay so if you are looking
at the volume balance flow rates you
have a flow rate 1 plus flow rate 2 is
equal to flow rate 3 plus flow rate flow
that's at steady state because there is
no accumulation in the unit but if there
is an unsteady state that means when you
are starting the unit at the beginning
of the time there will be some
accumulation but once it has reached a
steady state whatever comes in that is
the two flows inside will be equal to
whatever going out so f1 plus f2 is
equal to f3 plus f4 so this is a very
important equation so if you know F 1 F
2 you can knowing one stream quantity
you can calculate other stream quantity
let's call the volume balance similarly
you can do a species balance that means
you know that F 1 m contains C 1
concentration if to contain C 2
concentration of and F 3 contains C 3
concentration therefore contains C 4
concentration so if you are doing a
species balance if fund c1 is the
quantity of the species coming in in the
stream F 1 and F 2 C 2 is the quantity
of the species coming in in the stream 2
so this should be equal to the quantity
of the species going out that's on the
right hand side that is f 3 into C 3
that is quantity of the species going
out through stream 3 and F 4 C 4 is the
quantity of the species going out in
stream 4 so these 2 on the left should
match exactly with these 2 on the right
ok let's at steady state and no reaction
please remember no reaction if there is
reaction there is going to be changed so
if you are adding a chemical and that
chemical is getting reacted so it is
going into some other product so it
won't this will not match but if there
is no reaction then F 1 whatever is
coming in for the species should be
equal to whatever is going out at
so these two our equations are very very
very important if you are going to do a
mass balance for species as well as mass
balance for the volume okay so the most
important point is there is no reaction
there is no loss and no degradation so
you need to consider those aspects very
very clearly actually similarly just
like we did the mass balance you also
have something called energy balance or
you also have something called heat
balance okay in heat balance what
happens is whatever heat that's coming
in and there are heats going out and
there are heat generated because of
reaction or you're putting in some heat
and there are going to be heat loss to
the surroundings so their heat balance
is slightly complicated you are going to
have many streams for heat balance
I think we will talk about this in the
next class
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