PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila

Intramuros, Manila

MULTIPHASE BIOREACTOR
Multiphase bioreactors include, for instance, gas-liquid-solid and gasliquid-liquid reactions. In many important cases, reactions between gases and
liquids occur in the presence of a porous solid catalyst. The reaction typically
occurs at a catalytic site on the solid surface. The kinetics and transport steps
include dissolution of gas into the liquid, transport of dissolved gas to the catalyst
particle surface, and diffusion and reaction in the catalyst particle.

PACKED BED BIOREACTORS

The most common reactor configuration used for immobilized cells is that
of packed bed of particles. The advantages of packed beds include simplicity
of operation and reasonable high mass transfer rates. Problems in the operation
of packed beds include obstruction by uncontrolled cell growth and
compression of the particles leading to excessive pressure drops. For these
reasons simple packed bed reactors are mostly used for the case of non viable
cells.
Packed beds can either be run in the submerged mode (with or without
aeration) or in the trickle flow mode.
A variety of packings are available for this purpose, both polymer,
ceramic, glass and natural (wood or bark) in dumped and structured forms,
porous or non-porous in a variety of shapes and sizes. These give very high
surfaces for cell immobilization and thin films with minimal mass transfer
limitations can be formed. The flow velocities in the channels can be high to
eliminate external mass transfer limitation in the adjacent liquid film as well.
Simultaneously, plugging can be avoided, albeit at the cost of high pressure
drop.
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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Fixed beds in anaerobic operation (e.g. digestion with methane production)

can be run in recycle mode to avoid gas building up in the packing. With low
gas production rates, recycling is not needed, and a gradient of concentration
may be established. It should be remarked that as with gas absorbers or other
packed bed operations any maldistribution of the liquid flow will result in poor
performance (e.g. channeling). Plugging of the beds may occur as rapidly as
every 1 or 2 days and this makes periodic cleaning necessary. Injecting air and
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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

using a higher liquid flow rate for a short period will normally dislodge excess
biomass. This sudden burst of biomass in the effluent has to be separated (e.g.
by sedimentation) and collected for further treatment.

BUBBLE - COLUMN BIOREACTOR

In these reactors mixing circulation and aeration is performed by gas
injection and if needed by additional external liquid circulation to obtain the
required mixing pattern. Figure below, gives an example of a possible
configuration. This usually results in less shear for a given quality of mixing than in
stirred tanks. Air lifts give more vigorous recirculation for the same air flow, but
often lower oxygen transfer rates than bubble columns. To limit shear, small
bubbles can be used in aeration, but depending on conditions this may cause
excessive foaming and requires more energy for their generation at porous
distributors.
Special designs for immobilized cells have been proposed, that avoid the
problems associated with separation of particles at the reactor outlet

The concept of an air lift reactor

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

FLUIDIZED BED BIOREACTORS

One of the major problems with stirred tank reactors is the attrition of the
matrix resulting from the vigorous stirring required for proper suspension of
particles, and this becomes more problematic if the particles are heavier, larger
and fragile matrices such as gels are used. When high volume fractions of
biomass particles are preferred, and this obviously enhances the reactor
efficiency, fluidized bed technology offers many possibilities. Such reactors are
not very different from bubble columns, except maybe for the higher biomass
fraction.

Fluidized bed reactors (a) fluidized bed (b) tapered fluidized bed

In its simplest two-phase operation, a flow of liquid is directed through the

particles at velocities above the 'minimum fluidization velocity'. This is the
velocity at which the pressure drop over the bed equals the weight of the
particles per unit surface and they are lifted off their fixed bed state. At higher
velocities, the bed will expand and only at much higher velocities will particles
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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

be entrained by the liquid and the fluidized bed organization destroyed. The
settling rate drops as the solids fraction in the bed increases, and consequently
the minimum fluidization velocity is much lower than the settling velocity of a
single particle. Design of such systems in terms of adequate fluid velocities is not
very difficult, but in bioreactors of this type the size and density of the
aggregates or particles will depend on the growth and hydrodynamic
conditions and these are very difficult to predict accurately. The expansion or
minimum fluidization velocities are very sensitive to these two parameters. This
results in a complex coupled system which is not easily accurately described. If,
however, the supporting particles are rather heavy and measures are taken for
a stable film thickness, stable operation and easy design will be possible. Excess
biomass detached from the particles is entrained by the fluid and can be
separated from the effluent.

TRICKLED BED BIOREACTOR

Trickle bed reactors are three phase systems containing a packed bed of
heterogenous catalyst and flowing gas and liquid phases. One (or more)
reactant is provided in each feed liquid and gas phase, so that biochemical
reactions depends on contacting of liquid, containing the sparingly soluble
reactant from the gas phase, with the catalyst surface. Accordingly, the
performance of such reactors is substantially influenced by the physical state of
gas-liquid flow through the fixed bed and by the associated mass transfer
processes.

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

BIOREACTOR DESIGN
THE BIOREACTOR STEP
This is the step where bioconversion takes place. It is necessary to understand
general features of a typical bioreactor and how it might be operated.
Bioreactors generally have two important functions:
1. TO HOLD the substrate bed and TO PROTECT it against release of
microorganism to the surroundings and contamination from the
surroundings.
2. TO CONTROL, to the degree that is possible, the key environmental
conditions, such as the bed temperature and water activity, at values
which are optimal for growth and product formation by the
microorganism.

It is not possible simply to set the environmental conditions within the substrate
bed at the desired value. The growth of the organism will tend to change the
environmental conditions away from the optimal values and one must then
intervene in order to try bringing them back to the optimum.

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

However, once can only manipulate a limited number of variables that are
external to the bioreactor, called operating variables such as changing the
agitation regime (if the bioreactor is agitated), the temperature, flow rate, and
humidity of the inlet air (if the bioreactor is aerated), the addition of solutions or
substances or the temperature and flow rate of the cooling water (if the
bioreactor has cooled heat-transfer surfaces). The success of these external
interventions in bringing the bed conditions back to the optimum values
depends on the efficiency of the heat and mass transport processes within the
substrate bed.

The Physical Structure of Bioreactor System

The bioreactor contains three phases

The bioreactor wall;

A headspace full of gas, the extent of which depends on the bioreactor
type;
A substrate bed composed of particles and air within the inter-particle
spaces.

The bioreactor wall acts as a barrier to the outside environment. It allows

material transfer through holes in this wall. Also, partial energy transfer such as
conduction is greatly dependent on the materials from which the bioreactor
was constructed.
The headspace has functions such as allowing the air leaves the bed to reach
the air outlet of the bioreactor and also enables room for bed expansion and for
disengagement of particles and air. Furthermore, it allows space for particle
movement and air introduction through bed.
The substrate bed is the site of the bioreaction where the microorganism grows.

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Overview of Multiphase Bioreactor Types and Features

Group I: Bioreactors in which the bed is static, or mixed only very infrequently
(i.e., once or twice per day) and air is circulated around the bed, but not blown
forcefully through it. These are often referred to as tray bioreactors. These
typically consist of a chamber containing a large number of individual trays
which are typically open at the top and have perforated bottoms to increase
accessibility to O2 and which are stacked one above the other with a gap in
between.
Group II: Bioreactors in which the bed is static or mixed only very infrequently
(i.e., once per day) and air is blown forcefully through the bed. These are
typically referred to as packed-bed bioreactors. They are consist of a column
of cylindrical or rectangular cross section, oriented vertically, with a perforated
base plate on the bottom which supports a bed of substrate. Air is blown up
through the base plate.
Group III: Bioreactors in which the bed is continuously mixed or mixed
intermittently with a frequency of minutes to hours, and air is circulated around
the bed, but not blown forcefully through it. Two bioreactors that have this
mode of operation, using different mechanisms to achieve the agitation, are
stirred-drum bioreactors and rotating drum bioreactors. These typically
consist of a drum of cylindrical cross section lying horizontally. The drum is
partially filled with a bed of substrate, and air is blown through the headspace.
In rotating drums, the whole drum rotates around its central axis to mix the bed.
In stirred drums, the bioreactor body remains stationary and paddles or scrapers
mounted on a shaft running along the central axis of the bioreactor rotate
within the drum.
Group IV: Bioreactors in which the bed is agitated and air is blown forcefully
through the bed. This type of bioreactor can typically be operated in either two
modes, so it is useful to identify two subgroups. Group Iva bioreactors are mixed
continuously while Group IVb bioreactors are mixed intermittently with intervals
of minutes to hours between mixing events. Various designs fulfill these criteria,
such as gas-solid fluidized beds, the rocking drum, and various stirredaerated bioreactors.
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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Overview of Operating Variables

Operating variables are variables that the operator can manipulate in an
attempt to control the conditions within the bioreactor. The question of optimal
operating strategies for the various bioreactor types is covered in the individual
bioreactor. However, describing the parameters in general will include:

Aeration. Regardless of whether the air is blown forcefully through the bed
or circulated around the bed, it is possible to control the flow rate,
temperature, and humidity of the air supplied at the inlet to the
bioreactor or chamber. The costs of supplying air will depend on the
volumetric flow rate and the pressure drop in the bed, and the need to
heat or refrigerate the air. Pressure drop, which deals with packed-bed
bioreactors, since its importance is greatest for this type of bioreactor.

Environment. The conditions in the surroundings of the bioreactor can be

controlled. The bioreactor may be placed in a room or other location
where the air temperature, humidity, and circulation are controlled.
Alternatively, the bioreactor may be fitted with a water jacket. The flow
rate and temperature of the cooling water at the inlet of the jacket can
be controlled. Note that if the desired air or water temperatures are
different from the temperatures at which they are available, either
cooling or heating will be necessary, which entails extra costs.

Introduction. Additions can be made to beds that are mixed, even if only
intermittently; for example, water can be sprayed onto the bed during
mixing.

Agitation. In beds that are mixed, it is possible to control the frequency,

duration, and intensity (i.e., revolutions per minute of the agitator) of the
mixing.

The aim therefore is to select combinations of operating conditions that make

the best balance in: minimizing deviations from the optimum temperature;

Minimizing damage to the organism;

Minimizing deviations of the bed water activity from the optimum value;
Maximizing the supply O2 to the particle surface.

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

GROUP I BIOREACTORS
Basic Features, Design, and Operating Variables for Tray-type Bioreactors
Group I bioreactors, or tray bioreactors, represent the simplest technology for
biochemical engineering applications. They have been used for many centuries
in the production of traditional fermented foods such as tempe and in the
production of soy sauce koji.
Trays may be appropriate for a new process if the product is not produced in
very large quantities, if a produced-packet of fermented product can be sold
directly, or if labor is relatively cheap.

The tray chamber may be relatively small, such as an incubator, or it may

be a room large enough for people to enter;
The tray may be constructed of various different materials, such as wood,
bamboo, wire or plastic. In fact, a plastic bag might be used instead of a
rigid tray;
the bottom and sides of the tray may be perforated or not;
Water-cooled heat exchange surfaces might be incorporated.

The available design features for tray type bioreactors are:

The dimensions of the tray, namely length, width, and height;

The positioning of the trays within the bioreactor;
The presence of cooling surfaces within the tray chamber.

The available operating variables are:

The temperature, humidity, and flow rate of the air entering the tray
chamber and the velocity of circulation past the tray surface;
If cooling surfaces are present, then the temperature of the cooling water.

Note that, although this type of bioreactor is nominally static, the bed may be
mixed infrequently. For example, it is typical for the tray contents to be turned by
hand once or twice a day.

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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Heat and Mass Transfer in Tray Bioreactors

Depending on the situation, it may be appropriate to consider either an
individual tray or the whole-tray chamber as the bioreactor. For example, it
would be appropriate to treat the whole tray chamber as the bioreactor when
the trays are open to free gas and water exchange with their surroundings and
the temperature and humidity of the air in the tray chamber are carefully
controlled.
The question about optimum design of tray chambers has received little
attention. For example, quantitative information is not available about the best
way to position trays in the chamber. As a result, it is not possible to state what is
the best spacing to leave between trays in order to maximize volumetric
productivity (that is, the amount of product produced per unit volume of tray
chamber). Most attention has been given to the individual trays. As a
generalization, within an individual tray, large O2 and temperature gradients will
arise in the substrate layer during the fermentation.

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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Oxygen Profiles within Trays

Since in a tray bioreactor air is not blown forcefully through the trays, O2 and
CO2 can only move within the bed by diffusion. Potentially, due to the
temperature gradients that arise, there could be natural convection within the
void spaces within the bed.
The limitation of O2 movement in the bed to diffusion through the void spaces,
coupled with its simultaneous uptake by the microorganisms at the particle
surfaces, leads to the establishment of O2 concentration gradients within the
void spaces.
Ragheva Rao et al. (1993) proposed an equation to estimate the maximum
depth that a tray could be in order for the O2 concentration not to fall to zero at
any part in the tray during fermentation. They referred to this depth as the
critical depth (Dc, cm):

Where:

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YXO is the yield coefficient of biomass from O2 (g dry biomass/ g O2)

C is the concentration of O2 in the surrounding atmosphere (g/cm3)
D is the effective diffusivity of O2 in the bed (cm2/hr)
RXM is the maximum growth rate (g dry biomass / cm3 bed-hr)

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Temperature Profiles within Trays

Szewczyk (1993) derived a simplified equation that can be used to describe the
temperature profile within a tray bioreactor, from the central plane (z=0) to the
surface (z=1), when the top and bottom half of the tray are identical.
(

Where:

TS and Ta are the temperatures of the bed surface and surrounding air
(oC), respectively.
Z is the spatial coordinate expressed as a dimensionless fraction of the
total bed height.
NB is the Biot number, given by az/K were a is the heat transfer coefficient
for bed to air heat transfer at the top of the bed (W/m 2 oC), and k is the
thermal conductivity of the bed.
represents the temperature difference that would occur between the
bottom of the solid bed and the tray surface if there were no heat
transfer through the bottom of the tray. It is given by the equation.

Where: RQ is the volumetric heat production rate (W/m 3).

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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Conclusions
The layer of substrate in trays is limited to a bed height of around 5 cm by
considerations of heat and O2 transfer within the bed. Therefore scale-up of the
process cannot be achieved by increasing the bed height. The only manner to
scale up a tray process to large scale is to increase the surface area of the trays,
which is equivalent to saying that the large-scale process must use a large
number of trays of the same size as those in which the laboratory studies were
done. The use of large numbers of trays implies the necessity either for manual
handling or highly sophisticated robotic systems, both of which can be
inordinately expensive. However, in regions in which manual labor costs are low,
such tray-type processes may find applications.

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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

GROUP II BIOREACTORS
Basic Features, Design, and Operating Variables for Packed Bed Bioreactors
Some possible variations in the design include:

The column may have a cross section other than circular.

The column may lie horizontally, or for that matter, at any angle. This alters
the relative directions of the forces due to gravity and air pressure.
Then column may be aerated from either end. For a vertical column, the
air may enter the bed from either the top or bottom. Aerating from the
top avoids the fluidization of particles at high air velocities, but will
contribute to bed compaction since the air flow is in the same direction as
gravity.
The column may have a perforated tube inserted along its central axis,
allowing an extra air supply in addition to the end-to-end aeration.
However, this will only be effective for very small bioreactor diameters.
The column may be water-jacketed or heat transfer plates may be
inserted into the bed.

Packed-bed bioreactors with internal heat transfer plates will be referred to as

Zymotis packed-beds, using the name coined by Roussos et al. (1993), while
those lacking such plates will be referred to as traditional packed-beds

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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Taking the most common design, namely a vertical column in which the bed is
aerated from the bottom and without any internal perforated tubes, the
available design variables for a packed-bed are:

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the presence or absence of a cooling jacket or internal heat transfer

plates;
the height and width of the bioreactor. The height to diameter ratio can
vary over quite a wide range;
if internal cooling plates are used, their height and the spacing between
them.

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

The available operating variables are:

The aeration rate;

The temperature of the inlet air;
The temperature of the surroundings (which might be cooling water)

In a static bed, the relative humidity of the inlet air is not a useful
operating variable. The problem is that it is not practical to add water into an
unmixed bed in such a way as to distribute it evenly amongst the substrate
particles; therefore evaporative water loss must be minimized. If the air entering
the bed were not saturated with water, this unsaturated air would promote
evaporation and dry out the bed, eventually decreasing the water activity to
values unfavorable for growth and product formation. In order to minimize
evaporation, saturated air must be supplied at the air inlet, which removes
manipulation of the inlet air humidity as an available operating variable. Note
that the use of saturated air does not prevent evaporation from occurring within
the bed, but it does minimize evaporation compared to the use of unsaturated
air. It is possible to replenish water during the mixing events of intermittently
mixed beds, in which case unsaturated air can be used to aerate the bed.
Important phenomena that are affected by the values chosen for the design
and operating variables are:

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The axial and radial temperature gradients in the bed. In packed-beds it is

impossible to prevent temperature gradients from arising within the bed,
so the aim is generally to minimize the size of any temperature gradients.
The evaporation of water from the bed. Efforts must be made to minimize
evaporation in order to prevent the bed or parts of the bed from drying
out.
The pressure drop through the bed. This will depend on the bed height
and the degree to which the organism fills the inter-particle spaces, with
the resulting pressure drop affecting the design of the aeration system
and its operating costs, and maybe placing a limit on the bed height that
can be used.

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

In general, O2 supply to the particle surface will not be considered in the

selection of design and operating variables. The aeration rates that are chosen
on the basis of heat removal considerations will typically be high enough that
sufficient O2 supply is ensured. However, note that problems such as channeling
are possible, in which O2 transport to large parts of the bed can be limiting.

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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

Conclusions
Packed-bed bioreactors are the natural choice when the microorganism does
not tolerate mixing well. The major challenge in developing large-scale packedbed bioreactors for new applications will be to minimize the axial temperature
gradients.
There are two main strategies by which this can be done:

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to use traditional packed-beds but use a low bed height

to use a Zymotis-type bioreactor, with internal heat transfer plates.

PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

If the organism can tolerate infrequent mixing events, of the order of once
every few hours or even as infrequent as once per day, then the traditional
design should be chosen. These mixing events allow the pressure drop to be
decreased, and also the addition of water to replenish the water lost in
evaporation. Agitation is not a feasible option in the Zymotis packed-bed due to
the presence of the heat transfer plates.
If a traditional packed-bed is chosen, then the bed height will need to be
no more than say 20 cm to 1 m, in order to prevent high temperatures at the
outlet end of the bed. The other possibility, of using tall water-jacketed columns
of 15 cm or less in diameter, is unrealistic, since, to hold large amounts of
substrate, the bioreactors will either need to be very tall or a large number of
bioreactors will be needed.
If it is not desired to mix the bed at all, due to the sensitivity of either the
organism or the substrate to damage by mixing, then the Zymotis design should
be strongly considered, on the basis of considerations of the water balance. The
contribution of conduction to heat removal will decrease the axial temperature
gradient, and this will decrease the evaporation rate, as long as saturated air is
used at the air inlet. Further, the greater the sensitivity of the process to high
temperatures, the more the Zymotis bioreactor is indicated. For the same
bioreactor height, the maximum temperature reached in a Zymotis bioreactor is
lower than for the traditional bioreactor.
However, the Zymotis bioreactor does have some disadvantages in its
operability compared to the traditional bioreactor. Both bioreactors have a
potential problem with water condensing from the saturated outlet air onto the
exposed bioreactor surfaces above the substrate bed, and this condensate can
flood the top of the bed, causing O2 limitations in this region. This problem will be
greater with the Zymotis bioreactor than for traditional packed-beds if the
cooling plates extend above the top of the bed.

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PAMANTASAN NG LUNGSOD NG MAYNILA

University of the City of Manila
Intramuros, Manila

MULTIPHASE
BIOREACTOR

Jonathan P. Reyes
BSChE v
2012-20364

Submitted to:
Engr. Denvert C. Pangayo

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