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DEPARTMENT OF BIOTECHNOLOGY
RAJALAKSHMI ENGINEERING COLLEGE,THANDALAM
CHENNAI
Prepared by
Kavitha Vijayaraghavan
Lecturer, Department of Biotechnology,
Rajalakshmi Engineering College,Thandalam
BT 2353 BIOPROCESS ENGINEERING
AIM
This course aims to develop the skills of the students in the area of Bioprocess
Engineering. This will be a pre-requisite for a few elective courses and for project in
Bioprocess Technology.
OBJECTIVES
At the end of the course, the student would have learnt about stirred Tank
reactors and configuration of various reaches, and how to model and similar a
Bio process. This will help the student to undertake project in the area of Bio
process Technology.
UNIT I ANALYSIS OF STR 8
Stirred tank reactor - non-ideality, RTD and stability analysis, tanks in series and
dispersion models – application to design of continuous sterilizer.
UNIT II ANALYSIS OF OTHER CONFIGURATIONS 8
Packed bed reactor, airlift reactor, fluidized bed reactor bubble column reactors –
nonideality,
RTD and stability analysis.
UNIT III BIOREACTOR SCALE – UP 9
Regime analysis of bioreactor processes, oxygen mass transfer in bioreactors -
microbial oxygen demands; methods for the determination of mass transfer coefficients;
mass transfer correlations. Scale up criteria for bioreactors based on oxygen transfer,
power consumption and impeller tip speed.
Typ
e of Reactor
Continuously Stirred Run at steady state with continuous flow of reactants and
Tank Reactor (CSTR) products; the feed assumes a uniform composition throughout
the reactor, exit stream has the same composition as in the
tank
4. Good
control
5. Simplicity
of
construction
6 Low
operating
(labor) cost
7. Easy to
clean
Assumptions
In terms of conversion
Reactor Sizing
Given –rA as a function of conversion, –rA = f(X), one can size any type of
reactor. The volume of a CSTR can be represented as the shaded areas in the
Levenspiel Plot shown below:
Reactors in Series
Given –rA as a function of conversion, , –rA = f(X), one can also design any
sequence of reactors in series provided there are no side streams by defining the
overall conversion at any point.
Given –rA = f(X) the Levenspiel Plot can be used to find the reactor volume
FAo = 10 mol/min
CAo = 2 mol/dm3
X=?
Derive Equation
Because the reaction is elementary, the combined mole balance and rate law
becomes:
then we substitute numerical values for our variables and calculate a conversion
of:
FAo = 10 mol/min
CAo = 2 mol/dm3
At T=350 K
X=0.75
V= ? and k=?
In this problem we have to find a way to relate these two reactors. At first, this
question looks unsolvable, but then we recall the following relationship
between k1 and k2:
Derive Equation
k2V=3.3
Derive Equation
X=0.72
Problems that are over-specified.
FTo = 40 mol/min
CAo = 2 mol/dm3
k(400 K) = 0.1/min
This reaction follows the first order rate law: -rA = kCA
The activation energy (E) is 10 kcal/mol & the Arrhenius constant (A) is
3*104/min
This problem might confuse the student with excess information about the rate
constant, but there is a straight-forward solution.
Derive Equation
This reactor is useful for substrate solutions of high viscosity and for immobilized
enzymes with relatively low activity. However, a problem that arises is that an
immobilized enzyme tends to decompose upon physical stirring. The batch system is
generally suitable for the production of rather small amounts of chemicals.
The continuous stirred tank reactor is more efficient than a batch stirred tank reactor
but the equipment is slightly more complicated.
Continuous Sterilization
One method of continuous sterilization injects steam into the medium (no heat
exchanger). The medium stays in a loop for a predetermined holding time until the entire
medium is sterile.
Better heat economy comes from substituting heat exchangers for direct steam injection.
Instead of having a cold water stream to cool the sterile media, the lower temperature
unsterile media stream absorbs heat from the warm stream, cooling the sterile media.
A system for continuous sterilization has a holding coil for detention long enough to kill
all of the microorganisms. The medium from a make up vessel flows through the
exchanger, is held in the coil, and passes back through the heat exchanger, heating more
unsterile medium while becoming cool itself, as it is collected in a sterile fermenter.
This design would work only with an exchanger with infinite heat transfer area because
there is no driving force for heat transfer as the temperatures for the two streams
approach closely. A real design would have another small exchanger to raise the
temperature to the setpoint after the main exchanger has done all it can do. There is no
need for a cooler before entering the fermenter because it has a jacket or coils for
temperature control that can easily handle this load.
Heat economy is not important for a small pilot plant unit for continuous sterilization, so
direct steam injection is simpler. A heat exchanger is then needed with cooling water to
bring the medium back down quickly to a temperature at which it is not over cooked.
Advantages:
Uniform steam requirements throughout the duration of the sterilization
Simplified process control
Shorter sterilization time means less thermal degradation of medium
Disadvantages:
High demand for steam in a shorter period of time than batch
Concentration of media becomes dilute due to steam condensation
Since steam is actually dispersed in media, steam must be clean to avoid
contamination
High temperatures for short times are used in preparing nutrient media for industrial
fermentations and in pasteurizing milk, because this causes less damage to biochemicals
than more prolonged times at lower temperatures. This exploits the temperature effects
on activation energies because bacterial killing is affected by a temperature change more
than is heat destruction of biochemicals.
When the flow in a heat exchanger is countercurrent, the outlet temperature of the stream
being heated can approach the temperature of the hot stream to be cooled. There is an
attempt to show this in the sketch. There are gradients on the shell side as well.
The Shell and tube exchanger is not as well-suited to continuous sterilization as the plate-
and-frame type of exchanger.
Sandwich of Plates. This sketch did not turn out well. Much better sketch by Lawrence
Bernstone, 1995 The idea is that the countercurrent flow in alternate sections gives a
gradient from coolest to hottest in each plate of the sandwich. In chemical processing, a
packed bed is a hollow tube, pipe, or other vessel that is filled with a packing material.
The packing can be randomly filled with small objects like Raschig rings or else it can be
a specifically designed structured packing.
Applications
Another factor in performance, in addition to the packing shape and surface area, is the
liquid and vapor distribution that enters the packed bed. The number of theoretical stages
required to make a given separation is calculated using a specific vapor to liquid ratio. If
the liquid and vapor are not evenly distributed across the superficial tower area as it
enters the packed bed, the liquid to vapor ratio will not be correct and the required
separation will not be achieved. The packing will appear to not be working properly. The
height equivalent to a theoretical plate (HETP) will be greater than expected. The
problem is not the packing itself but the mal-distribution of the fluids entering the packed
bed. These columns can contain liquid distributors and redistributors which help to
distribute the liquid evenly over a section of packing, increasing the efficiency of the
mass transfer.[1] The design of the liquid distributors used to introduce the feed and reflux
to a packed bed is critical to making the packing perform at maximum efficiency.
Columns used in certain types of chromatography consisting of a tube filled with packing
material can also be called packed columns and their structure has similarities to packed
beds.
Packed bed reactors
Packed bed reactors can be used in chemical reaction. These reactors are tubular and are
filled with solid catalyst particles, most often used to catalyze gas reactions. [2] The
chemical reaction takes place on the surface of the catalyst. The advantage of using a
packed bed reactor is the higher conversion per weight of catalyst than other catalytic
reactors. The reaction rate is based on the amount of the solid catalyst rather than the
volume of the reactor
If gas is introduced at the bottom of the bed three phase contacting is achieved.
In contrast the scale up of trickle bed reactors is easy and might be chosen for a
process inspite of the advantages of the 3 phase fluidized bed reactor.
The 3 phase fluidized bed reactors so far developed commercially for processes
such as hydrogenation of petroleum residues using bed of particles of various
sizes.
Reactors with small molecules tend to produce large bubbles.These are similar to
bubble column
slurry reactors.
A three phase fluidised bed using large particles requires high liquid flow rates in
order to maintain the particles in the fluidised state but have the advantage of
producing smaller bubbles and hence
large interfacial area for mass transfer.
One of the areas of uncertainity in 3 phase design is the mixing that occurs in gas
and liquid phases.
As particle size increases flow approximates to plug flow
The overall rate of the reaction calculated from the 3 phase fluidised bed reactor is
approximately one tenth of the rate calculated for agitated slurry reactor.
The main reasons are very poor effectiveness factor,
relatively smaller external surface area for mass
transfer caused by using larger particles.
Although the three phase reactor does not appear to perform favorably compared
to agitated tank sluury
reactor it should be remembered that fluidised bed does not have a sealing or other
mechanical complications associated with agitators.
RESISTANCES
The various resistances active in a 3 phase fluidised bed reactor are
The first commercial use of a fluidized-bed reactor, in the 1920s was for the
gasification of coal to supply CO and H, for the production of synthetic
chemicals.
The technology has been developed also for a number of other processes,
including other catalytic reactions for the production of chemicals and synthetic
gasoline by the Fischer-Tropsch process, and noncatalytic processes for the
roasting of sulfide ores, and the incineration of solid waste.
Fluidized-bed and similar technology has also been used for nonchemical
operations in heat exchange, drying of solids, and coating processes analogous to
chemical vapor deposition.
Consider a bed of solid particles initially fixed in a vessel, and the upward flow
through the bed of a fluid introduced at many points below the bed, as indicated
schematically . The rate of flow of fluid is characterized by the superficial linear
velocity us, that is, the velocity calculated as though the vessel were empty. At
relatively low values of us, the bed remains a fixed bed of particles, although it
expands somewhat as us, increases.
As u, increases further, a point is reached at which the bed begins to “lift”.
Beyond this point, over a range of increasing us, the action of the multiphase fluid
+ solid region (bed) may resemble that of a vigorously boiling liquid with an
apparent upper surface from which rising fluid disengages.
This action is referred to in general as fluidization of the bed (in the case above, a
“bubbling fluidized bed”.
As U, increases still further, solid particles become elutriated from the fluidized
region by entrainment in the rising fluid.
At sufficiently high values of us, the entire bed of particles may be entrained with
the fluid and carried overhead out of the vessel. Other types of intermediate
behavior occur, usually undesirable, and we have simplified the picture
considerably.
When a chemical reaction occurs in the system, each of these types of behavior
gives rise to a corresponding type of reactor. These range from a fixed-bed
reactor, to a fluidized-bed reactor without significant carryover of solid particles,
to a fast-fluidized-bed reactor with significant carryover of particles, and
ultimately a pneumatic-transport or transport-riser reactor in which solid particles
are completely entrained in the rising fluid. (BFB)
(Pneumatic Conveying) (Fast Fluidized)
At higher gas velocities the BFB transforms into TB-no distinct bubbles,much
churning and violent solid movement.The surface of the dense bed fades and
solids are increasingly found in the lean region above the bed.The flow of gas is
between PF and BFB.The concentration of solids in the upper lean region can be
represented by exponential decay function.
In a fast-fluidized bed, the fluidization velocity is very high, resulting in
significant entrainment of solid particles. Consequently, there is a concentration
gradient of solid particles through both the bed and freeboard regions.Continuous
addition of fresh solid particles may be required for some operations(e.g., coal
gasification).
The performance is typically described using both a fluidized bed model and a
freeboard-reaction model. Applications of fast-fluidized beds are in fluidized-bed
combustion and Fischer-Tropsch synthesis of hydrocarbons from CO and H2.
In pneumatic flow, fluid velocities are considerably greater than the terminal
velocities of the particles, so that virtually all of the particles are entrained. The
vessel may be extremely tall, with no solid recirculation (e.g., coal combustion),
or it may provide for solid recirculation with external cyclones.
The process stream is extremely dilute in solid particles because of the high
volumeof gas passing through the “bed.” Fluid-catalyzed cracking of gasoil is an
important example of pneumatic transport with external recirculation (and
regeneration) of catalyst pellets.
A spouted bed is characterized by a high-velocity spout of gas moving up the
center of the bed, carrying particles to the top. This action induces particle
circulation, with particle motion toward the wall and downward around the spout
and toward the center. The particles in a spouted bed are relatively large and
uniformly sized.
Spouted beds have been used for drying and low-temperature chemical-treatment.
Examples are the low-temperature roasting of agricultural products, and particle-
coating and crystal-growth operations.
EXAMPLES OF REACTIONS
Reactions in moving-particle reactors in general, and in fluidized-bed reactors in
particular, may be catalytic or noncatalytic. That is, the particles may be catalyst
particles or reactant particles.
Catalytic cracking of gasoil: an impetus for the development of fluidized-bed
reactorsover 50 years ago was the desire to make the catalytic cracking of
gasoil(to gasoline) a continuous process, in spite of the rapid deactivation of the
catalyst particles by coke and tarry deposits. Originally, both the catalytic-
cracking reactor (“cracker”) itself and the catalyst regenerator were fluidized-bed
reactors,with solid particles moving continuously between the two in an overall
continuous process, but more recently the cracker is made a pneumatic-transport
reactor.
Production of acrylonitrile by ammoxidation of propylene (SOHIO process):
2NH3+ 3O2 + 2C2H2 -> 2C2H2N + 6H2O.The fluidized-bed process for this
reaction has several advantages over a fixedbed process. First, the process is
highly exothermic, and the selectivity to C,H,N is temperature dependent. The
improved temperature control of the fluidized bed operation enhances the
selectivity to acrylonitrile, and substantially extends the life of the catalyst, which
readily sinters at temperatures in excess of 800 K.
Oxidation of napthalene to produce phthalic anhydride:
C10H10 + 02 à C10H10O3 à CO + H2
Proper control of temperature is required to limit
napthaquinone production and avoid the runaway (and
possibly explosive) reaction which leads to theproduction of CO, and H,O. A
fluidized-bed is thus preferred over a fixed-bed process.
Production of synthetic gasoline by the Fischer-Tropsch process:
nCO + 2nH2 à (C,H,) + nH2O
This is another example of a highly exothermic process which requires strict
temperature control to ensure appropriate selectivity to gasoline, while limiting the
production of lighter hydrocarbons. Again, the enhanced temperature control provided by
a fluidized-bed system greatly improves the feasibility of this process.
Noncatalytic roasting of ores such as zinc and copper concentrates:
2ZnS + 302 à 2ZnO + 2S02
The fluidized-bed process replaced rotary kilns and hearths; its primary advantages
are its higher capacity and its lower air requirement, which leads to a product gas richer
in SO, for use in a sulfuric acid plant.
Noncatalytic complete or partial combustion of coal or coke in fluidized-bed
combustors:
C + O2 à CO2
C+1/2O2 àCO
These reactions may serve as a means of regeneration of coked catalysts. Both
reactions are exothermic, and the improved temperature control provided by a fluidized
bed is critical for regeneration of catalysts prone to
sintering.
The advantages and disadvantages of moving-particle reactors may be considered
relativeto the characteristics and operating conditions of fixed-bed reactor.
Advantages
(i) Mode of operation: operation can be made continuous with respect to both the
processing fluid and the solid; this allows, for example, for the continuous regeneration
of a deactivating catalyst.
(ii) Thermal: there is near-uniformity of T throughout the bed, which allows for better
control of T and avoidance of hot spots in highly exothermic reactions;the uniformity of
T is due to such things as the high degree of turbulence(resulting in relatively high heat
transfer coefficients), and the large
interfacial area between fluid and small particles.
(iii) Chemical performance: the use of relatively small particles (e.g., 0.1 to 0.3 mm) can
result in lower pore-diffusion resistance in solid particles and an effectiveness factor (q)
much closer to 1; by itself, this, in turn, results in a smaller catalyst holdup.
Disadvantages
(i) Mechanical: abrasion causes erosion of pipes and internal parts (e.g., heat transfer
surface); attrition of particles leads to greater entrainment and elutriation,requiring
equipment (cyclones) for recovery; these mechanical features lead to higher operating
and maintenance costs, as well as greater complexity.
(ii) Fluid-mechanical: There is a larger (-AP), requiring greater energy consumption;the
complex flow and contacting patterns are difficult to treat rationally, and create
difficulties of scale-up from small-diameter, shallow beds to large-diameter, deep beds.
(iii) Chemical performance: in fluidized-beds, there is a “bypassing effect” which leads to
inefficient contacting; fluid in large bubbles tends to avoid contact with solid particles;
this leads to a larger catalyst holdup and/or lower conversion,which may even be lower
than that predicted on the basis of BMF,which in turn is lower than that based on PF, the
turbulence and resulting backmixing may result in adverse effects on selectivity, for
example, depressing the intermediate in a series reaction.
DESIGN
Typical design requirements include calculations of catalyst or reactant solid
holdup for a given fractional conversion and production rate (or vice versa),
The bed depth, the vessel diameter and height, and heat transfer requirements.
The reactor model may also need to account for conversion in regions of the
vessel above(“freeboard” region) and below (“distributor” region) the bed, if there
is a significant fraction of the solid in these regions, and/or the reaction is very
rapid.
The overall design must consider special features related to the superficial
velocity, and the flow characteristics of the solid and fluid phases within the
vessel.
AB: (- ΔP) increases with increasing u, , as the bed retains the character of a fixed
bed, with l g increasing somewhat.
BC: (- ΔP) is relatively constant, as the bed becomes fluidized; B is the point of
incipient fluidization at urnf.
CD: (- ΔP) decreases with increasing us, from C, at which elutriation begins, to
D, at which point the particles may be said to be entrained (at ut).
Derive the Design equation for a packed bed reactor.(Also give the design
considerations).
The bulk density, ρb, of the bed is the ratio of the total mass W to the total volume V:
ρb = W/V
The bed voidage, s, is the ratio of the interparticle void space to the total volume V:
where ρp is the density of the particle, equation 8.5-1. From equations 21.3-2 and 8.5-3,
When a fluid flows through a bed of particles, interactions between fluid and particles
lead to a frictional pressure drop, (- AP). Calculation of (- AP) enables determination
of both L and D, for a given W (or V). This calculation is done by means of the
momentum balance, which results in the pressure gradient given by
where x is the bed-depth coordinate in the direction of flow, f is the friction factor, u is
the superficial linear velocity, pf is the density of the fluid, and d; is an effective particle
diameter. Integration of equation 21.3-4 on the assumption that the second term on the
left is constant results in the pressure drop equation: -
where L is the depth of the bed (L = x at the outlet); note that ΔP = P(outlet) -
P(inlet) is negative. In equation 21.3-5,dp; is the effective particle diameter, which
accounts
for shape, defined as
dp = 6 X volume of particle/external surface area of particle
For a spherical particle of diameter dP, dp’ = dP, and for a solid cylindrical particle,
dh = 3d,l(2 + d,lL,) or 1.5d,, if dp/Lp << 2, where L, is the length of the particle.
For the friction factor, we use the correlation of Ergun
Re’ = dp’uρf / μf
Re’ = dp’G / μf
G = 4 m /πD2
where m is the mass flow rate, and A, is the cross-sectional area of the bed.
If D or L is specified (for a given W), (-ΔP) may be calculated from above 5 equations.
Alternatively, we may use these equations to determine D (and L) for a specified
allowable value of (-ΔP ). The equations may be solved explicitly for D (or L):
D6 –βКD2 – К = 0
К = 64 αm2W/ π3 ρf dp(-ΔP) ρb
Above Equation provides the value of the bed diameter D for a given allowable pressure
drop, (-ΔP), a value of W calculated as described later, and known
values of the other quantities. Since (α,β, and К are all positive, from the Descartes rule
of signs there is only one positive real root of the above equation . If the
equations are solved for L instead of D, a cubic equation results.
In the choice of a value for the allowable (-ΔP) on the one hand, or for D (or L)
on the other (given W), there is a trade-off between the cost of the vessel and the cost
of pumping or compressing the fluid. The smaller D, the greater the L/D ratio and the
greater (-ΔP); thus, the cost of the vessel is less, but the cost of pumping is greater, and
conversely.
Fixed beds cannot use very small size particles because of plugging whereas
fluidized bed can use small size particles.
DESIGN
Many factors must be considered for optimum design and the
best design is the one which uses two different reactor types
in series.
How to account for the non isothermal behavior for packed beds.
How to account for non ideal flow of gas in the fluidized beds.
STAGED ADIABATIC PACKED BED REACTORS
With proper interchange of heat and proper gas flow,staged adiabatic packed bed
systems become a versatile system which is able to approximate any desired
temperature progression.
The reacting conditions should follow optimal temperature progression.
For any preset number of stages the optimizing operations reduces to minimizing
the total catalyst for a given conversion.
OPTIMUM TWO STAGE PACKED BED REACTOR
We are able to reduce this 3-d search to 1-d search where Ta alone
is guessed.
Guess Ta
Move along the adiabatic line till the following condition is satisfied.
out
∫ ∂/∂T (1/-ra’)dXa = 0
in
Cool to point c which has the same rate of reaction as point b thus,
(-ra’ )leaving the reactor = ( -ra’)entering next reactor
Move along the adiabatic from point c till the criterion given in second point is
satisfied giving point d.
All else being equal cold shot cooling has the advantage of lower cost since heat
exchangers are not required.Cold shot cooling is practical only when feed
temperature is very much below the reaction temperature.
Packing supports: The support must be sufficiently strong to carry the weight of a
reasonable height of packing and it must have ample free area to allow for flow of
liquid and gas with a minimum of restriction.
Packing restrainers: These are necessary when gas velocities are high and they guard
against the lifting of packing during a sudden gas purge. Heavy screens or bars may
be used.
The flow might be upwards or downwards, but upflow is more desirable as the fluid
will contact/wet the packing uniformly (avoids short circuiting/channeling) and also
the contact time will be more than that of downflow.
The PBR follows the plugged flow pattern, thereby only radial mixing will occur and
there won’t be any axial mixing (/backmixing) inside the reactor. Hence the residence
time distribution will be uniform as all the fluid particles literally travel the same path
length inside the reactor.
The substrate concentration will be more near the fluid inlet and the product
concentration will be less. As the reaction progresses the product concentration
increases and hence near the outlet the substrate concentration will be less and the
product concentration will be more. This important characteristic makes the PBR
useful for carrying out product inhibition reactions.
In product inhibition reactions, there will be competitive inhibition as the product
present initially competes with the substrate for binding with the enzyme. However,
as only a small portion of product will initially compete with the substate in the PBR,
the product inhibition reactions can successfully be carried out in these reactors.
Pressure drop:
It is the decrease in pressure from one point to another point along the length of the
reactor.
Tube convergence, divergence, turns and the flow rates affect the pressure drop.
It is given by the Ergun equation:
High flow rates in small tubes give larger pressure drop, low flow rates in large tubes
give lower pressure drops.
High pressure drops are undesirable because it will result in both high pumping
energy costs and non-uniform pressure of the gas reactant, affecting the overall
reactor performance.
The pressure drop in the reactor can be reduced by using larger catalyst particles.
However smaller particles will increase the surface area of contact. So the diameter of
the particle used should be optimum favouring a low pressure drop as well as giving a
good surface area for contact.
Performance equations:
These are also called as design equations as they are useful for reactor design.
Considering mass balance:
Rate of substrate diffusion out of bulk liquid = rate of substrate disappearance by
reaction within the pellet
4πR2ks(S-Ss) = (4/3) πR3η (Ss, Ps) v (Ss, Ps)
Where,
R= radius of pellet (biocatalyst)
ks = saturation constant
S = substrate concentration in bulk liquid
Ss = substrate concentration on the exterior surface of the pellet
η = effectiveness factor
v = intrinsic rate of product formation
Ps = product concentration on surface of pellet
Considering material balance on substrate:
u.ds/dz = - ((1-ε)/ε)η (Ss,Ps)v (Ss,Ps)
Where,
ε = void fraction
1-ε = fraction occupied by the solid particles in the packing
If η = 1, then Ss = S; i.e. no mass transfer resistance will be there between the liquid
and solid phase when effectiveness is 1.
In design, the number of necessary theoretical equilibrium stages is first determined
and then the packing height equivalent to a theoretical equilibrium stage, known as
‘Height equivalent to a theoretical plate (HETP)’ is determined.
Total packing height = (number of theoretical stages) x (HETP)
Advantages:
1. High conversion per unit mass of catalyst
Disadvantages:
1. Poor temperature control
2. Poor pH control
General Characteristics
The two major uses of the residence time distribution to characterize nonideal
reactors are
1. To diagnose problems of reactors in operation
2. To predict conversion or effluent concentrations in existing/available reactors
when
a new reaction is used in the reactor.
Three concepts were used to describe nonideal reactors: the distribution of
residence times in the system, the quality of mixing and the model used
to describe the system.
~The time the atoms have spent in the reactor is called the residence time
of the atoms in the reactor.
~In any reactor, the distribution of residence times can significantly affect
its performance.
~The residence-time distribution (RTD) of a reactor is a characteristic of
the mixing that occurs in the chemical reactor.
~Not all RTDs are unique to a particular reactor type; markedly different
reactors can display identical RTDs.
~The RTD exhibited by a given reactor type yields distinctive clues to the
type of mixing occurring within it and is one of the most informative
characterizations of the reactor.
The quantity E(t)dt is the fraction of fluid exiting the reactor that has spent between
time t and t+dt inside the reactor.
SLURRY REACTORS
SLURRY REACTORS
The design of gas liquid solid reactor is very much dependent on the size of the
solid particles chosen for the reaction.
Agitated tanks can be used for large size particles because of the high local
velocities produced by the impeller.
The impeller needs to be properly designed and positioned at the bottom of the
tank so that it will keep the solids in
suspension and disperse the incoming gas.
A slurry reactor is a multiphase flow reactor in which the reactant gas is bubbled
through a solution containing solid catalyst particles.
In slurry reactor the catalyst is suspended in liquid and gas is bubbled through the
liquid.
In modelling slurry reactors we assume that the liquid phase is well mixed and the
catalyst particles are uniformly distributed and gas phase is in plug flow
Let the gas consist of pure reactant A ( typically H2) and let
the reaction take place at the interior of the catalyst, the
reaction being pseudo first order with rate constant k1.
Let
a : Gas liquid interfacial area per unit volume of the
dispersion.
εg = volume fraction of gas bubbles.
εl = volume fraction of liquid.
εs = volume fraction of solid.
εg + εl + εs = 1
db = 6 εg /a for bubbles
dp = 6/ap for particles
db = 6 εg /a for bubbles
dp = 6/ap for particles
The mass transfer and chemical reaction steps take place in series. Hence each
step should proceed at the same rate as the
overall process.
Since the rate of the reaction is the same the overall rate of the
reaction can be obtained as
From the above equations the volume of the reactor can be found
out knowing the value of the rate of the reaction.
10. Mixed flow of G and batch L.
For component A
Input = Output + Disappearance
Fao = Fao(1- Xaexit) + (-ra’’’’)Vl
For component B
Input = Output + Disappearance + Accumulation
0 = 0 + dNb/dt + (-rb)Vr
(-rb)Vl = -dNb/dt
-rb = (1/ Vl ) -dNb/dt = -dCb/dt
- ra = -rb/ b
-rb = b(-ra) = -dCb/dt
-ra = 1/ b (-dCb/dt)
(-ra)Vl = (-ra’’’’)Vr
Thus
Vl/b (-dCb/dt) = (-ra’’’’)Vr = FaoXaexit
USES
Hydrogenation of
1. Fatty acids over supported nickel catalyst.
2. 2-butyne-1,4-diol over pd-CaCO3 catalyst.
Oxidation of
1. C2H4 in inert liquid over a pdCl2 –Carbon catalyst.
2. SO2 in inert water over activated carbon catalyst.
Hydroformation
1.CO with high molecular weight olefins with cobalt complex bound polymers.
Ethynylation
1. Reaction of acetylene with formaldehyde over a CaCl2 supported catalyst.
TANK REACTORS
Tank reactors usually employ mechanical agitation to bring about more intimate
contact of the phases, with one phase being dispersed in the other as the
continuous phase.
The gas phase may be introduced through a “sparger” located at the bottom of the
tank;this is a circular ring of closed-end pipe provided with a number of holes
along its length allowing multiple entry points for the gas.
Tank reactors are well suited for a reaction requiring a large liquid holdup or a
long liquid-phase residence time. The operation may be continuous with respect
to both phases, or it may be semicontinuous (batch with respect to the liquid).
The simplest flow pattern for each phase is BMF. The reactor may be single-stage
or multistage and the flow for the latter may be cocurrent or countercurrent.
In the case of a liquid-liquid reaction, each stage typically consists of a mixer
(with agitation, for reaction) and a settler (without agitation, for separation by
gravity).
Tank reactors equipped with agitators (stirrers, impellers, turbines, etc.) are used
extensively for gas-liquid reactions, both in the traditional chemical process
industries and in biotechnology.
In comparison with nonagitated tank reactors equipped only with spargers,
mechanically agitated tank reactors have the advantage of providing a greater
interfacial area for more efficient mass transfer
The enhanced mixing also ensures a nearly uniform temperature within the vessel,
an advantage for processing temperature-sensitive materials, and for control of
product yield and selectivity in complex systems.
A major disadvantage is the cost of the energy required for agitation.
Furthermore, since the mass transfer characteristics are related to agitation
characteristics (e.g., stirrer rate), there are difficulties of scale-up.
Typical values of gas-liquid interfacial area (ai and ai’) for various types of
vessels
Tower(Spray,Plate) Tank
Agitated Sparger
ai 1000 200 20
ai’ 100 180 20
vl/vr 0.1 0.9 0.98
Values of the ratio Vl / Vr given in table emphasize that most of the volume in a
tower reactor is occupied by the gas phase, and conversely for a tank reactor.
This means that ai >> ai’ in a tower and ai= ai’ : in a tank.
For a tank reactor the ideal flow pattern is BMF for each phase (gas and liquid).
Important considerations are the dispersion of gas bubbles within the liquid phase,
and the agitator power required for this.
The h/D ratio is usually about 1, but this is exceeded if the stages in a multistage
arrangement are stacked vertically. Gas is usually fed to the reactor below the
agitator through a distributor which may be a perforated plate or pipe ring
(sparger).
The type of agitator also can affect bubble size, and, thus, mass transfer
characteristics.
The most common types are rotating flat paddle mixers, with straight or inclined
blades, and a turbine, with several flat blades attached to a disc (turbine).
The diameter of the blades is usually about 35% of the vessel diameter (D).
Several vertical baffles, each with a width of up to 10% of D, are attached to the
wall of the vessel around its circumference.
CONTINUITY EQUATION
Continuity equation for A in the gas phase (BMF).Since the gas phase is in BMF,
the continuity equation corresponding to and based on the entire vessel of
volume V=Ach = πd2/4 h
Rate of input = Rate of output + Rate of transfer
of A by bulk flow of A by bulk flow transfer of A to
liquid film
YainGAc = YaoutGAc + Naai’Ach
The overall material balance around the tank is again given by equation
G/P ( pain –paout ) = L/b ( Cbin –Cbout) + L(Caout-Cain)
CORRELATIONS FOR DESIGN PARAMETERS FOR TANK REACTORS
Before we can apply the continuity or design equations for tank reactors
developed we must have the means of determining values of the parameters
involved. These include gas holdup, g, mass transfer coefficients, kAl , and kAs,
and gas-liquid interfacial area, ai or ai’.
L(D) = ql /Ac
G(D) = Fain,/0.21Ac
V(D) = (1 - εg)V
Usg(D) = qg/Ac
Oxygen is needed by cells for respiration. Oxygen used by cells in suspension must be
available as dissolved oxygen. Since oxygen solubility is quite small, about 6 to 7 mg/L
under normal cultivation conditions, metabolic oxygen requirement is supplied on a as
needed basis by continuous aeration of culture medium. Actively respiring yeast requires
about 0.15 g O2 (g cell)-1 h. At a cell concentration of 10 g L-1, medium saturated with air
can support less than 30 seconds worth of metabolic oxygen. That is, a continuous supply
of oxygen must be maintained in any viable aerobic manufacturing process. In this
Chapter, we will first get a quantitative appreciation for metabolic oxygen demand,
followed by methods used in calculating rates at which oxygen is transfered from sparged
air. We will then examine methods useful in characterizing oxygen mass transfer
coefficient. Finally we will evaluate bioreactor operation and design based on oxygen
transfer capability.
Metabolic oxygen demand of an organism depends on the biochemical nature of the cell
and cultivation conditions. Oxygen need is usually satisfied in most cells if the dissolved
oxygen concentraiton in the medium is kept at about 1 mg/L. If the oxygen level is
allowed to fall far below this value, oxygen consumption rate decreases with concomitant
decrease in biochemical energy production, and as a result cell growth rate also
decreases. We described this behavior in Section 4-4. The value of oxygen concentration
above which growth rate is at the maximum was described as the critical oxygen
concentration, . Characteristic values are summarized in Table 5-1.
Organism in mg L-1
E. coli at 37 C 0.26
S. cerevisiae at 30 C 0.13
Penicillium sp at 24 C 0.78
The oxygen requirement for growth is expressed best in the the parameter, yield
coefficient, YX/O2. It represents the amount of oxygen required to grow one gram of cells.
Typical values summarized in Table 5-2, show that approximately 0.7 to 1 g of oxygen is
needed to produce 1 g of cells. In the same table respiration quotient is also included.
YX/O2 qO2
Organism Substrate
[g (g cell)-1 h] [g O2 (g cell)-1 h]
E. coli Glucose 1.1 0.20
S.cerevisae Glucose 0.98 0.30
Candida utilis Glucose 1.32
Pennicillium sp. Glucose 1.35 0.18
Hybridoma
CHO cell line
The transport of oxygen through the gas and liquid films are equal at steady state. They
can be expressed by
where subscript G and L refer to gas and liquid phases respectively. The terms, NO2G and
NO2L are oxygen transfer expressed in g O2 h-1, A is interfacial area and CDO is oxygen
concentration expressed in g O2 per unit volume. At the interface, equilibrium between
the liquid and gas phase oxygen is reached. That is
Because of low oxygen solubility and the fact that kG is much higher than kL,
The subscript L in NO2 has been dropped to note that the above represents overall transfer
of oxygen. The driving force in the above consists of the difference between bulk oxygen
concentrations in the two phases; the first term represents the concentration of oxygen in
the liquid which is in equilibrium with the bulk gas phase oxygen. If air is the gas
medium, this term will equal to 7 mg/L at 35 C.
When the above oxygen transfer is applied to an entire volume of a bioreactor, A will
represent the total interfacial area and kL will represent an average mass transfer
coefficient. The concentrations will be bulk gas and liquid phase oxygen concentrations.
If we divide the above equation by volume of liquid phase, V, the resulting term will
represent the amount of oxygen transfered per unit volume per unit time --- which is in
the same units as the rate expressions we saw in last chapter. Since the rate is due to a
physical phenomena, let us distinguish it by the symbol, RO2. That is,
The term, kL A represents the product of mass transfer coefficient and interfacial area
available for mass treansfer. In a bioreactor, air is sparged and the liquid is agitated to
break up the bubbles so that interfacial area can be kept high to enhance rate of oxygen
transfer. In such systems, the area, A, is not easily measured or estimated. But, the term
consisting of the product - mass transfer coefficient and interfacial area - is more readily
measured. Further more, it is convenient to use interfacial area per unit volume, a, rather
than total area, A because rate of oxygen transfer is expressed per unit volume of
bioreactor, similar to rate of cell growth, which is reported on a volumetric basis. Hence,
area per unit volume, a, is combined with the mass transfer coefficient, kL and is given by
the term, kLa. In Eq(5-5) the term, can be replaced by oxygen solubility at bioreactor
conditions, .
The above will be our working equation for describing transfer of oxygen from gas phase
to growth medium. In order for us to calculate oxygen transfer rate (OTR), we need the
mass transfer coefficient, kLa , solubility of oxygen in the medium, and the dissolved
oxygen concentration in the medium, CDOL. In the last chapter we had used the notation,
CDO to describe dissolved oxygen concentration. In the discussion above, there was a need
to make a distinction between gas and liquid phase concentration. In Eq (5-5), one notes
that both concentrations are expressed on the basis of liquid phase. Hence, from here on
we will drop the subscript L. In situations where we need to make a distinction between
the two phases, we will re-introduce the subscript L and G.
Let us now consider the case of oxygen balance within a bioreactor in which cells are
growing and in the process consuming oxygen. There is a continuous inflow of air at a
constant volumetric flow rate. The liquid broth is agitated by a Rushton agitator (flat
blade stirrer ). Le the metabolic oxygen uptake rate be qO2 and cell concentration is X. Let
us examine the reactor system over a sufficiently short period that we can treat X as a
constant. Consider oxygen balance over the liquid phase of the bioreactor.
The concentration, CDO is readily measured using an dissolved oxygen electrode. A later
segment of the course on Biosensors, will deal with principle of measurement and
construction of DO electrodes.
If oxygen being supplied is in exact balance with the oxygen consumed by the cells, we
expect the dissolved oxygen concentration to remain constant; that is, the derivative in
Eq(5-7) will vanish. That is,
One useful application of the above is in estimating the maximum cell concentration a
particular bioreactor is capable of supporting in terms of oxygen supply. See the example
below.
Example 5-1.
A bioreactor has an oxygen mass transfer coefficient capability of 400 h-1. What is the
maximum concentration of E. coli that can be grown aerobically in this reactor.
Respiration rate of E. coli is 0.35 g O2 (g Cell)-1 h-1. Critical oxygen concentration is 0.2
mg/L. Assume oxygen saturation with air to be 6.7 mg/L.
Solution
Factors Affecting KLa The mass transfer coefficient is strongly affected by agitation
speed and air flow rate. In general,
Note that the mass transfer coefficient increases with agitation speed and air flow rate.
Measurement of KLa
Most common method of measuring kLa is to conduct experiments in the bioreactor when
cells are absent, or cell concentration is low so that consumption by cells can be
neglected. The latter condition is present immediately after inoculating the bioreactor.
Consider Eq (5-7) under these conditions:
If we allow steady state to occur, the dissolved oxygen concentration will reach saturation
value, and the concentration-time profile will be flat, as shown in the diagram.
Fig 5-2 Oxygen Profile During a Transient. The responses will be exponential, rather
than straight lines.
If the oxygen source (air) is replaced by nitrogen, the resulting response of the system is
described by the above equation with the term, set to zero. That is,
The solution to the above is
If one plots the response on a semi-log plot, the slope will equal to the negative of mass
transfer coefficient. It is relatively a simple experiment and the data analysis is also easy
to do. When other type of transient mass transfer experiments are conducted, the above
equations should be suitably modified. For example for the case of nitrogen to air switch,
we should suitably modify the solution because the initial condition is now different.
Case Studies
You are part of a tech service team asked to evaluate if the available 10,000 liter
fermentor is adequate to produce 10 kg/day of a recombinant protein using a strain of E.
coli that expresses the protein as 20 % of cellular protein. In order to enhance plasmid
stability, the nutrients are manipulated to give a low specific growth rate is 0.2 h-1. The
oxygen demand is 0.15 g O2/g cell - h. Assume that the r-protein formation is cell growth
associated.
Data: The lag phase is 4 hours. Typical clean-up time following a fermentation batch and
preparation for the next batch is 8 hours. The plant runs three shifts. Cell yield on
substrate is 0.55 g cell/g substrate. Available support services can supply inoculum of a
maximum of 6 kg of cells every 24 hour period. Maximum KLa for the available
-
fermentor is 500 h 1. Fermentor accessories are capable of handling cell concentrations of
60 g/L. Assume any other parameters you need to complete the calculation.
Assumption: Critical oxygen conc. is 0.2 mg/L and DO at air saturation is 6.4 mg/L
Next to determine the inoculum level. The maximum batch growth phase is 12 h.
Substitute in growth eqn, and assuming nutrients are present to support exponential
growth during the 12 h period,
For 10,000 liters, we will need 18.7 kg every 12 h. Since only 6 kg is available, max.
protein that can be produced is
Solution B: Now let us allow batch times to be longer than 12 h, meaning that there
might not be a harvest every day. Since it is advantageous to use the max. inoculum
concentration, select X0 = 0.6 g/L. This value is obtained by diving 6 kg of cells in
10,000 L. Max. cell concentration is fixed due to aeration requirements. Use the batch
growth eqn to find the batch growth time of 17.7 h. Hence 20.6 kg or r-protein will be
produced every 29.7 h which gives a 24 h production rate of 16.6 kg.
What alternative way of running reactor would you recommend to achieve the production
target?
You are part of a tech service team asked to evaluate if the available 10,000 liter
fermentor is adequate to produce 10 kg/day of a recombinant protein using a strain of E.
coli that expresses the protein as 20 % of cellular protein. In order to enhance plasmid
stability, the nutrients are manipulated to give a low specific growth rate is 0.2 h-1. The
oxygen demand is 0.15 g O2/g cell - h. Assume that the r-protein formation is cell growth
associated.
Data: The lag phase is 4 hours. Typical clean-up time following a fermentation batch and
preparation for the next batch is 8 hours. The plant runs three shifts. Cell yield on
substrate is 0.55 g cell/g substrate. Available support services can supply inoculum of a
maximum of 6 kg of cells every 24 hour period. Maximum KLa for the available
-
fermentor is 500 h 1. Fermentor accessories are capable of handling cell concentrations of
60 g/L. Assume any other parameters you need to complete the calculation.
Assumption: Critical oxygen conc. is 0.2 mg/L and DO at air saturation is 6.4 mg/L
Solution A: Lag phase and clean-up/ prep time is given as 12 h. If a batch is to
completed within each 24 h period, production is limited to 12 h per day. If this is not a
limitation, one can optimize production by varying batch time. Let us first evaluate
assuming 12 h batch times.
If max. cell concentration of 20.6 g/L is obtained, amount of r-protein produced is = (0.2)
(0.5) (20.6) = 2.06 g/L. 50% of cell dry matter was assumed to be protein. Hence in
10,000 liters, we will produce 20.6 kg.
Next to determine the inoculum level. The maximum batch growth phase is 12 h.
Substitute in growth eqn, and assuming nutrients are present to support exponential
growth during the 12 h period,
For 10,000 liters, we will need 18.7 kg every 12 h. Since only 6 kg is available, max.
protein that can be produced is
Solution B: Now let us allow batch times to be longer than 12 h, meaning that there
might not be a harvest every day. Since it is advantageous to use the max. inoculum
concentration, select X0 = 0.6 g/L. This value is obtained by diving 6 kg of cells in
10,000 L. Max. cell concentration is fixed due to aeration requirements. Use the batch
growth eqn to find the batch growth time of 17.7 h. Hence 20.6 kg or r-protein will be
produced every 29.7 h which gives a 24 h production rate of 16.6 kg.
What alternative way of running reactor would you recommend to achieve the production
target?
Compartmental models
If metabolite corrected arterial blood curve and dynamic PET data are available from the
time of injection to the time where all important changes in tracer kinetics have been
seen, and the data is of sufficient quality, then it may be possible to estimate the
parameters of a complete model, including perfusion, blood volume in tissue vasculature,
transport, specific binding or reaction rate etc. In practice this can be done only in very
simple cases, e.g. with labeled water which just flushes in and out of tissue. As is
mentioned above, it is possible and desirable to either measure some of the parameters in
separate studies, e.g. blood volume using [15O]CO, or constrain them to literature values,
or to reduce the model. Most often there is no need to measure all the parameters, but just
one key parameter which correlates with the desired property in usual conditions.
Plasma compartment
To be precise, the plasma is not a compartment of the model. The concentration of tracer
in the plasma is measured, and applied to the compartment model as a known input
function. However, plasma compartment is still usually counted as one of the
compartments.
The metabolite corrected arterial plasma curve is the input to the compartment model. If
the intravascular activity is accounted for in the calculation, the whole blood
concentration, containing metabolites, should be used for that. If metabolite corrected
plasma curve is used instead of uncorrected whole blood curve to correct for vascular
blood volume fraction, blood contribution at late times is underestimated, which could
result in the artificial presence of an apparent additional tissue compartment
[Lammertsma 2002].
Methods for quantitation of perfusion (blood flow, f) with freelydiffusable tracers are
based on Kety's analyses of the principles of inert gas exchange. Tracers such as
[15O]H2O, [15O]butanol, [11C]butanol and [18F]fluoromethane are used for this purpose.
Also a single breath inhalation of [15O]CO2 produces an arterial bolus of [15O]H2O.
The kinetic model for measurement of glucose transport and phosphorylationrate in brain
is based on a three-compartment model.
The description of the time course of the ligand in tissue rquires a modelthat accounts for
the different components contributing to the signal. These are free ligand in plasma, free
ligand in tissue, CF, ligand in tissue which is not specifically bound, CNS, and ligand
specifically bound to the receptor, CB [Schmidt and Turkheimer 2002]:
Use of 4-compartment model is not feasible given the large number of rate constants to
be estimated, and the kinetically undistinguishable compartments for specific and non-
specific binding. The model is simplified under the assumption of a rapid equilibrium
between free and non-specifically bound compartments that produces a single
compartment of free + non-specifically bound ligand:
Although for most ligands k3' and k4 cannot be estimated with a reasonable degree of
accuracy, their ratio is usually more stable.
Enzyme reactors
Batch reactors generally consist of a tank containing a stirrer (stirred tank reactor, STR).
The tank is normally fitted with fixed baffles that improve the stirring efficiency. A batch
reactor is one in which all of the product is removed, as rapidly as is practically possible,
after a fixed time. Generally this means that the enzyme and substrate molecules have
identical residence times within the reactor, although in some circumstances there may be
a need for further additions of enzyme and/or substrate (i.e. fed -batch operation). The
operating costs of batch reactors are higher than for continuous processes due to the
necessity for the reactors to be emptied and refilled both regularly and often. This
procedure is not only expensive in itself but means that there are considerable periods
when such reactors are not productive; it also makes uneven demands on both labour and
services. STRs can be used for processes involving non-immobilised enzymes, if the
consequences of these contaminating the product are not severe. Batch reactors also
suffer from pronounced batch-to-batch variations, as the reaction conditions change with
time, and may be difficult to scale-up, due to the changing power requirements for
efficient fixing. They do, however, have a number of advantageous features. Primary
amongst these is their simplicity both in use and in process development. For this reason
they are preferred for small-scale production of highly priced products, especially where
the same equipment is to be used for a number of different conversions. They offer a
closely controllable environment that is useful for slow reactions, where the composition
may be accurately monitored, and conditions (e.g. temperature, pH, coenzyme
concentrations) varied throughout the reaction. They are also of use when continuous
operation of a process proves to be difficult due to the viscous or intractable nature of the
reaction mix.
All reactors would additionally have heating/cooling coils (interior in reactors (a), and
(d), and exterior, generally, in reactors (b), (c), (e) and (f)) and the stirred reactors may
contain baffles in order to increase (reactors (a), (b), (d) and (e) or decrease (reactor (f))
the stirring efficiency. The continuous reactors ((c) -(f)) may all be used in a recycle
mode where some, or most, of the product stream is mixed with the incoming substrate
stream. All reactors may use immobilised enzymes. In addition, reactors (a), (b) and (e)
(plus reactors (d) and (f), if semipermeable membranes are used on their outlets) may be
used with the soluble enzyme.
The expected productivity of a batch reactor may be calculated by, assuming the validity
of the non -reversible Michaelis -Menten reaction scheme with no diffusional control,
inhibition or denaturation (see reaction scheme [1.7] and equation (1.7). The rate of
reaction (v) may be expressed in terms of the volume of substrate solution within the
reactor (VolS) and the time (t):
(5.1)
Therefore:
(5.2)
On integrating using the boundary condition that [S] = [S]0 at time (t) = 0:
(5.3)
(5.4)
Therefore;
(5.4a)
and
(5.4b)
Also
(5.4c)
(5.5)
The change in fractional conversion and concentrations of substrate and product with
time in a batch reactor is shown in Figure 5.2(a).
Figure 5.2. This figure shows two related behaviours.
(a) The change in substrate and product concentrations with time, in a batch reactor. The
reaction S P is assumed, with the initial condition [S]0/Km = 10. The
concentrations of substrate (??? and product (-----------) are both normalised with respect
to [S]0. The normalised time (i.e. t? = t Vmax/[S]0) is relative to the time (t? = 1) that would
be required to convert all the substrate if the enzyme acted at Vmax throughout, the actual
time for complete conversion being longer due to the reduction in the substrate
concentration at the reaction progresses. The dashed line also indicates the variation of
the fractional conversion (X) with t?.
(b) The change in substrate and product concentrations with reactor length for a PBR.
The reaction S P is assumed with the initial condition, [S]0/Km = 10. The
concentrations of substrate (???) and product (-----------) are both normalised with
respect to [S]". The normalised reactor length (i.e. I? = lVmax/F, where Vmax is the
maximum velocity for unit reactor length and I is the reactor length) is relative to the
length (i.e. when I? = 1) that contains sufficient enzyme to convert all the substrate at the
given flow rate if the enzyme acted at its maximum velocity throughout; the actual
reactor length necessary for complete conversion being longer due to the reduction in the
substrate concentration as the reaction progresses. P may be considered as the relative
position within a PBR or the reactor's absolute length.
Types of Reactors
In an enzyme reactor, the highest specific enzyme activity is desirable. It is
considered an added bonus if the support that is used also aides in separation. One
approach is to use a molecular sieve as the support and pulse the reactor bed with the
alternating passage of substrate solution and water. The result is that bands of unused
substrate and product progress down the column. It so happens that the enzymes for
which this technique would be useful are also those which in some cases benefit in
having the enzyme immobilized on a porous support.
In a combined CSTR/UF reactor the enzymes are immobilized in that they can not
leave the reactor because of the filtration unit. This allows continuous processing with
free enzymes in the CSTR. The Ultra Filtration Unit contains a membrane which
provides a semipermeable barrier which allows products and unreacted substrate, if there
is any, to pass through while holding back the enzyme. There are other possibilities for
similar reactors, such as combined reactor-separators. However, the combined CSTR/UF
reactor has proven useful for several types of reactions where a typical immobilized
enzyme would not be as effective. One example of this is for the conversion of
benzylpenicillin to 6-aminopenicillanic acid by penicillin amidase.
Continuous packed bed reactors are the most widely used reactors for immobilized
enzymes and immobilized microbial cells. In these systems, it is necessary to consider the
pressure drop across the packed bed or column, and the effect of the column dimensions
on the reaction rate. There are three substrate flow possibilities in a packed bed and they
are illustrated below:
The recycling method is advantageous when the linear velocity of the substrate
solution affects the reaction flow rate. This is because the recycling method allows the
substrate solution to be passed through the column at a desired velocity.
For industrial applications, upward flow is generally preferred over downward flow
because it does not compress the beds in enzyme columns as downward flow does. When
gas is produced during an enzyme reaction, upward flow is preferred.
A continuous packed bed reactor has the following advantages over a batch packed
bed reactor:
Recycle Reactor
A recycle reactor is a reactor that is not seen very often, but is very important to
consider when studying immobilized enzymes. It is very important to chemical
engineering because it allows some substrates to be processed, which could not be
processed using other reactor types. An example of a recycle reactor can be seen below:
In a recycle reactor, a portion of the product stream is recycled and mixed with the
inlet flow to the reactor. If the entire product stream is recycled back to the inlet stream,
then it is called a total recycle reactor. This can obviously only be used in a batch
process, because if the entire product stream is recycled back into the reactor in a
continuous reactor, the volume of the reactor would increase to infinity. Therefore, we
will only consider partial recycle streams in a continuous reactor on this page.
This type of rector is used when you have a substrate that cannot be completely
processed on a single pass, such as with an insoluble substrate. These reactors continue to
move the same substrate through the reactor so that the effective contact time is high
enough to allow the substrate to be processed. Recycle reactors also allow the reactor to
operate at high fluid velocities. This is important because it minimizes the bulk mass
transfer resistance to the transport of the substrate. It is important to remember that a
recycle reactor is simply a reactor, such as a CSTR or fluidized-bed reactor, with a
recycle stream.
Ultrafiltration Membrane Devices
This device is suitable for a substrate of high molecular weight and a product of low
molecular weight. Since the enzyme used here is soluble, no improvement in the stability
of the enzyme can be expected. A hollow fiber device can also be used and its
characteristics are essentially the same as those of an ultrafiltration membrane.