TECHNICAL PAPER

Stirred Bioreactor Engineering for

Production Scale, Low Viscosity
Aerobic Fermentations: Part 1
By: Dr. Alvin Nienow
Senior Technical Consultant
The Merrick Consultancy

Merrick & Company

2450 S. Peoria Street Aurora, CO 80014-5475
Tel: 303-751-0741 Fax: 303-751-2581
www.merrick.com

January 2012

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

TABLE OF CONTENTS
S ection

Page

I ntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Engineering Issues in Stirred Bioreactors, Part 1 2
Mass Transfer of Oxygen into the Broth and Carbon Dioxide out 3
Hold - up and Foam Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Heat Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Summary . . . . . . . . . . . . .
R eferences . . . . . . . . . . .
N omenclature . . . . . . . . .
Tables . . . . . . . . . . . . . .
F igures . . . . . . . . . . . . . .
REMAINDER TO COME

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Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

Introduction
There are many examples of important bioprocesses that fall into the category of low viscosity aerobic
fermentations. They include the use of genetically-modified bacteria such as Escherichia coli to give bulk
chemicals such as 1,3-propanediol; and E. coli and Pichia pastoris for the production of proteins for medical
purposes. Indeed, though biofuels such as bioethanol, biobutanol and biogas are made under anaerobic
conditions, biodiesel can also be produced aerobically from genetically-modified E. coli. Other examples include
Saccharomyces cerevisiae for the manufacture of Bakers yeast and Corynebacter glutamicum for valine and
lysine production as animal feed additives.
The bioreactor (fermenter) of choice for such processes uses mechanical agitation and a typical traditional
stirring configuration based on Rushton turbines is shown in Fig 1a in diagrammatic form. Such fermenters have
been in use for at least 50 years and are commonly up to 250 m3 in scale or even larger for the manufacture of
many commercially important products. Fig 1b shows a photo with some people inspecting the internals in a
smaller scale industrial bioreactor. In this case, the impellers are of the wide-blade, high solidity ratio type which
is one of the type more commonly used today as a result of much research which has shown that changing
the agitator from the Rushton turbine to newer types can lead to significant improvements in the fermentation
process.
In these series of articles, the mixing issues which have to be considered when designing or operating such
fermenters will be discussed. In particular, the reasons why modern impellers are replacing the traditional
Rushton turbine by retrofitting into extant industrial equipment or have become the impellers of choice when
new plant is built will be explained. These impeller developments have been largely ignored in chemical and
biochemical engineering textbooks and in general even in the refereed journals except for a few specialist
exceptions. It is also not the intention to give detailed design details or methods of calculation. These aspects are
adequately covered in standard textbooks, especially that by Vant Riet and Tramper, Basic Bioreactor Design1.
The essence of such decisions comes from recognising that the issues can all be considered as bioprocess
scale-up where information obtained generally on a much smaller scale in the laboratory or pilot plant is used to
establish the desired commercial scale operating conditions. In other words, the industrial scale bioreactor has
to provide a suitable environment for the organism to grow and produce, based on the work conducted on this
smaller scale. In general, it is not possible to mimic on the industrial scale exactly the conditions found in the
smaller scale, so inevitably scale-up is a compromise. Essentially, however, this compromise is best understood
if it is recognised that each cell is itself a mini-factory converting nutrients, generally carbon based, into the
desired product. Thus the total production rate depends on production rate per cell multiplied by the number
of cells in the fermenter times the size of the fermenter. If the overriding importance of providing the correct
environment for the cell is recognised, scale-up, though indeed a compromise, is based on that concept rather
than arbitrary scale-up rules related to fluid dynamics, which essentially ignore the well-being of the cell. That is
the approach recommended in this series of articles.
The equipment used to obtain this information on the desired environment for the cell is indicated in Fig 2. At
the two smallest laboratory scales, the shaken microwell or shake flask (Fig 2 a and b) are used. The biological
parameters that may be determined in them are shown in Table 1. To find the optimum, many experiments
must be undertaken to establish the correct value of each of the many parameter; and this type of equipment is
ideal for such a requirement. It is also useful to establish the sensitivity to variations from that optimum as such
variations are bound to occur on the commercial scale. These variations arise because the environment in the
250 m3 stirred reactor is clearly not going to be as spatially homogeneous as the small volumes found in the
shaken microwell and shake flask. One of the big advances that has been made in recent years in developing
bioprocesses has been the ability to both measure and control many of these parameters in each reactor even
at these small scales. The papers of Buchs and co-workers, starting with one from 2011,2 give an excellent
indication of the developments in this area of allowing quantitative data for engineering purposes to be obtained
at these small scales.
As also shown in Table 1, some other biologically-specific parameters must be determined at the larger stirred
bench scale (Table 1b) as shown in Fig 2c in order to be useful. Fed-batch bioreactors are ones in which
additional growth medium is added over time, thereby increasing the cell concentration that can be achieved (as
well as the volume of medium). Thus, though the amount of oxygen that each cell requires to function properly
can be determined at the very small scale, to get a satisfactory indication of how that oxygen will be supplied
Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

in the commercial plant especially under fed-batch conditions really requires experiments to be done in similar
equipment. Essentially, that is linked to the need to use stirring to provide the energy for oxygen transfer with
air sparged from the base (specified by the mass transfer coefficient, kLa, as set out in more detail later) rather
than by shaking and from headspace aeration respectively. The potential for the energy input from the impeller
to damage the organism, often referred to as shear damage can also be assessed in such relatively small scale
stirred bioreactors. This possibility comes about because though the bench scale bioreactor is small compared
to the commercial one, even at this scale, the turbulence in the flow (which is discussed further below) that
impacts on the cell is similar at the small scale and the large. So the size of the cell to the scale of the turbulent
flow is also similar.
Having the information on the bioprocess of interest at the scales indicated in Figs 1a to 1c, good engineering
must then be used to determine suitable conditions at the production scale. These conditions should match
sufficiently closely those shown to be optimum at the bench scale with respect to cell and product concentration.
Thus, the desired temperature, pH, dissolved oxygen concentration, etc, must be achieved by the agitation and
aeration system in the bioreactor. The agitator provides the energy which gives rise to the turbulent liquid motion
required for these conditions to be achieved. In particular, the dispersion of the air must be done so that the
oxygen transfer rate, OTR, is able to meet the oxygen required by the cells to function properly. The turbulent
flow also homogenises the contents of the fermenter so as to maintain the various operating parameters within
the range that ensures the cells produce a similar bioprocess performance at the commercial scale to that
obtained at the small.
To give confidence that the commercial plant is going to achieve similar results to the smaller scales, operation at
the pilot plant scale shown in Fig 2d is also often undertaken. This overall approach is bioprocess scale-up with
the cell and its local environment as the key. The aim of much current research is to establish ways of going from
as small a scale as possible to the commercial scale whilst minimising work at intermediate scales, in particular to
eliminating the pilot scale stage. This approach is greatly enhanced if the smaller scales, especially in the stirred
bench scale bioreactor, are conducted in such a way that important parameters such as specific power (W/kg)
are similar to those that will be used on the large scale. Choosing sensible parameters in this way for the bench
scale is often called scale-down. A good scale down protocol greatly eases scale up
The remainder of these articles aim to help understand the interaction between the fluid motion generated by
different agitators under aerated conditions with variations in speed and power input; and how they change with
scale. This understanding is important for the design of new equipment; and retrofitting and solving operational
issues on that already extant. To aid this understanding it is useful to subdivide this overall task into a sub-set of
smaller issues. These issues will now be discussed.

Engineering Issues in Stirred Bioreactors

Many of the engineering issues are generic and apply to all aerobic bioprocesses (and indeed gassed chemical
reactors in general). They can be considered as physical parameters; and those most relevant to bacterial
fermentations are listed in Table 2. Table 2a sets out the quantitative parameters required for design whilst
Table 2b lists those parameters which aid understanding and have helped improve large scale operation and
design. The parameters in Table 1 on the other hand are specific to the organism being grown and will usually
be different for each case. Achieving satisfactorily the biological parameters required by the cell in Table 1 by
judicious design and appropriate selection of the parameters in Table 2 is essentially the task of the engineer,
especially with respect to scale-up. The final process engineering specification of the fermenter will be the size
(diameter, T (m), height, H (m)), the impeller type(s), number and size, D (m), the power needed to be imparted to
the broth, P (W) and the aeration rate, QG (m3 s-1). The way these values and the parameters set out in Table 2a
are determined will now be discussed.
For the microbial fermentations being considered here, the viscosity of the growth medium with the cells in it (the
fermentation broth) essentially does not go much higher than that of water. With such low viscosities, the flow
in the fermenter is turbulent at the 5 L bench, i.e. Reynolds number, Re =ND2/ > ~ 104 where is the broth
density (kg m-3), , its viscosity (Pa s), D,, the impeller diameter (m) and N, its speed (rev s-1). In practice, Re
increases with increasing scale. However, as the flow is turbulent, the actual value of the Reynolds number does
not matter and turbulent flow theories can be used to analyse the fluid mechanics in the bioreactors across the
scales. The topics listed in Table 2 will now be considered for such flows.
Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

Mass Transfer of Oxygen into the Broth and Carbon Dioxide out
The transfer of oxygen from air into a fermentation broth has been used since the 1940s when depth
fermentations were first established. It is one of the most important aspects of fermenter operation because
oxygen is only sparingly soluble in water and therefore in the medium, which largely consists of water. If the
supply of oxygen into the broth ceases, its concentration in the broth would generally fall below the desired
value in less than a minute. Thus, the overall oxygen demand of the cells throughout the batch or fed-batch
fermentation must continually be met by the oxygen transfer rate, OTR (mol O2 m-3 s-1); and the demand increases
as long as the number of cells is increasing. Thus, a maximum oxygen transfer rate must be achievable and this
depends on the mass transfer coefficient, kLa (s-1, though units of min-1 are also often used), and the driving force
for mass transfer, CL (mol O2 m-3). Thus,

OTR = kLa. CL 1

For oxygen transfer, the driving force, CL, conceptually is the difference between the oxygen concentration
in the liquid film around the air bubbles (the concentration in equilibrium with the partial pressure of oxygen in
the bubble) and that in the broth. The latter concentration must always be held above a critical dO2 value as
determined at the well-mixed bench scale. This concentration is usually expressed as a % of saturation with
respect to air as measured by a dissolved oxygen probe (% dO2). Though the critical value is often less than 10%
dO2 (and sometimes close to zero), the set value is often as high as 40% dO2. This higher value is to ensure that
dO2 never falls below the critical value throughout the fermenter since spatial homogeneity is difficult to achieve at
the commercial scale as discussed qualitatively above and quantitatively later. In practice, more oxygen transfer
can be achieved by increasing the driving force by raising the O2 partial pressure in the incoming gas stream
either by imparting a back-pressure on the bioreactor or by adding extra oxygen to the sparged air, preferably as
a separate flow.
Roughly, for every mole of O2 taken up by a cell, 1 mole of carbon dioxide, CO2, is produced. This ratio of moles
CO2 produced to O2 consumed is called the respiratory quotient, RQ, and as suggested here it is generally ~ 1.
Because CO2 is very soluble in the broth, especially compared to oxygen, it dissolves. The value of kLa is similar
for both O2 transfer from air to the broth and CO2 from it; but the high solubility, CO2 makes it much more difficult
to strip out. However, stripping of dissolved CO2 is very important because above a certain value of dissolved
CO2 (pCO2 > ~ 100 mbar), a reduction in fermentation rate or productivity is generally observed.
In addition to the driving force, the other parameter that the engineer can manipulate to control the rate of mass
transfer is the kLa. In low viscosity systems, kLa is only dependent on two parameters. These are, firstly, the
power input, P (W), into the fermenter, mostly from the impeller, and the air flow rate, QG (m3 s-1). It has been
shown that if the power input from the impeller when air is being sparged, Pg (W) is normalised in terms of the kg
of broth, Pg/M (W kg-1) in the fermenter, kLa can be correlated with this parameter at different scales. The specific
power input into the fermenter from stirring is numerically equivalent to the mean specific energy dissipation rate,
(T)g (W/kg); and because this is a fundamental parameter in the modern understanding of turbulence, it will be
used here in the rest of these articles. Thus, Pg/M / (T)g. Generally, for economic and biological reasons for
these types of fermentation, the specific power (mean specific energy dissipation rate) from the impeller is about
1 to 5 W kg-1.
The airflow rate impacts in the same way across the scales if the superficial air velocity, vS (m s-1) through the
fermenter is used, where vS = QG/A where AT (m2) is the cross-sectional area of the fermenter and AT = T2/4 where
T (m) is the diameter of the fermenter. However, the amount of broth and the number of cells in the fermenter
increases in proportion with its volume. As a result so does the volume of oxygen required and the amount of
carbon dioxide produced. Therefore in order to satisfy the mass balance for O2 transfer in and CO2 out, the
volumetric flow rate of air needs to be kept essentially constant. If this flow rate is expressed on a per minute
basis, a typical practical value is about 1 vvm (where vvm is the volumetric flow rate of air at standard conditions
in m3 min-1 per m3 broth in the bioreactor). Thus,
vS = (vvm/60)(volume of broth, m3)/(X-sectional area of the bioreactor, m2) 2

The combination of (T)g and vS selected must together be sufficient to produce the necessary kLa where

kLa = A(T)ag(vS)b 3
kLa is difficult to determine experimentally especially on the large scale but within the accuracy achievable, this
equation is found to be independent of the number of impellers and their type and also of scale3; and a and b
Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

are usually about 0.5 0.1 for low viscosity broths. On the other hand, the numerical value of A (which is NOT
dimensionless) is extremely sensitive to composition. Thus, a typical value of kLa would be about 0.1 to 0.2 s-1 in
water with the addition of antifoam lowering it by a factor of up to 2; and salts increasing it up to x4 for the same
values of (T)g and vS. It is important to point out at this stage that though Equ 3 does not depend on impeller
type, the value of (T)g and vS that can be efficiently utilised does. Thus, impeller choice is very important if the
mass transfer requirements are to be met and this aspect will be discussed in the next article.
As pointed out earlier, the value of kLa is similar for both O2 transfer in and CO2 transfer out. Thus, provided
scale-up is undertaken at constant vvm (or close to it), the driving force for transfer of O2 and of CO2 will remain
essentially the same across the scales. As a result, the total volumetric gas flow rate into the bioreactor should
also be able to strip out the CO2 to give the same partial pressure of CO2 in the exit gas and pCO2 in the broth on
scale-up as on the small scale, thus preventing potential problems with high values of this parameter. In addition,
as the air volumetric flow rate scales with fermenter volume, at constant vvm, vS increases with the linear scale-up
ratio (approximately with Tcommercial scale/Tbench scale), thereby enhancing kLa if constant (T)g scale-up is also used.

Hold up and Foam Formation

There is a down side to the higher superficial velocity on scale-up. These higher superficial gas velocities
increase hold-up (hold-up is essentially the proportion of the fermenter taken up by gas bubbles of different O2
concentration). Higher hold-up means loss of fermenter capacity as cells are only producing in the broth and not
in the gas phase. Even more problematic is that the high vS increases the tendency to form a stable foam, which
further lowers productivity and if not controlled, may lead to broth being driven out of the bioreactor into the exit
pipe, in extreme cases causing shut down. The usual way of handling such problems is to use one of a variety
of anti-foams4. Their use has two disadvantages. They are expensive and, as mentioned above, they lower kLa.
It has been shown that the certain modern impellers of the type discussed later reduce the foaming tendency
compared to Rushton turbines5. Though not so well documented, experience at the industrial scale suggests that
retrofitting to these other impellers has increased kLa by about 20 to 30% at the same (T)g and vS because less
antifoam has been used. If retrofitting is carried out, monitoring the use of antifoam is a useful way of establishing
the change in running costs and also perhaps explaining the higher kLa that may well be found in practice.

Heat Transfer
Accurate temperature control is very important in fermentation processes as cells are very sensitive to that
parameter which should normally be held between about 35 to 40C. The oxygen uptake rate largely determines
the metabolic heat release QH (W kg-1) so that

QH 4.6 x 102 OUR 4
This cooling load has to be removed by heat transfer at an equivalent rate given by

QH.M = U AH u 5
where U is the overall heat transfer coefficient (typically about 2000 to 3000 W m-2 C-1), u (C) is the difference
between the temperature of the cooling water and the broth temperature (about 35 to 40C) and AH (m2) is
the heat transfer area available. U is hardly affected by the agitation conditions though larger D/T impellers
associated with lower power number, Po, impellers (as discussed later) maximise the inside heat transfer
coefficient for a given (T)g.
Overall, at the commercial scale, heat transfer is often a problem as the cooling load scales with the volume
of the reactor, i.e., approximately reactor diameter T3 whilst cooling surface area scales with T2. Thus, if only
a cooling jacket as shown in Fig 3a is used on the larger scale, the area/volume goes down compared to the
bench scale so that cooling coils are often required and sometimes cooling baffles (Fig 3b). Inability to meet the
cooling requirements at the large scale is a very serious problem because it is extremely expensive to resolve and
cannot be achieved by increasing the agitation intensity as the overall heat transfer coefficient, U is insensitive
to it. Thus, if it is necessary to increase QH because it is insufficient to meet the cooling requirements of the
fermentation, either AH or u must be increased. The former requires the whole fermenter construction to be
modified and the latter needs refrigeration of the cooling water. It is clearly better to design with a high safety
margin with respect to the area in the first place. In a particular industrial example with which I was involved, the
rate of oxygen transfer was increased to meet the oxygen demand of the organism by introducing a slow oxygen
feed through a separate sparger (which incidentally is the best way of using oxygen to give an enhanced driving
force). That approach was very successful as a way of enhancing oxygen transfer but the heat release was such
Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

that the temperature could no longer be controlled. As a result, the nutrient feed to the fed-batch fermentation
had to be slowed down below the maximum rate now achievable with the higher rate of oxygen transfer.

Summary
In the Introduction, the need to consider the cell as the productive source in a bioreactor is introduced. In Part
1, those engineering parameters which have to be satisfied if cells are to grow satisfactorily at the large scale
are discussed. In particular, they are the provision of oxygen in the broth at an appropriate concentration; and
the need to strip out to a low concentration, the carbon dioxide that is produced at a rate governed by the rate at
which oxygen is consumed by the growing cells. The critical parameters in these two processes are the specific
power input from the stirrers and the airflow rate, of which increases in both increase the mass transfer coefficient
and of the latter, the driving force for mass transfer of O2 and CO2. The air flow rate also impacts on the amount of
gas held up in the bioreactor and the tendency for foam to form, both of which can reduce its productive capacity.
Finally, the heat evolved at a rate determined by the rate the organism takes up oxygen needs to be removed in
order for the bioreactor to be cooled in order to operate at the desired temperature is discussed. The need to be
rather conservative with the area available for cooling at the large scale is emphasized.
In Part 2, the modern impellers that have been introduced into industry in recent years will be discussed. In
particular, their impact on two aspects will be emphasized. The first topic will show how improved mass transfer
can be achieved by the correct choice of impellers, thereby obtaining a higher volumetric productivity from a
bioreactor. The second topic will show that there is an inevitable temporal and spatial increase in the range of
temperatures and concentrations of nutrients, dissolved oxygen, pH, etc., experienced by the cells on the larger
scale even if the mean value is closely controlled to coincide with that determined at the small scale. However, by
a suitable feed strategy and choice of impellers, it will be seen that these variations can be greatly reduced, again
giving an improved performance.

Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

References
1. Vant Riet, K and Tramper, J, Basic Bioreactor Design, Marcel Dekker, Inc., New York, USA, 1991.
2. Huber, R, Roth, S, Rahmen, N and Bchs, J. Utilizing high-throughput experimentation to enhance specific
productivity of an E.coli T7 expression system by phosphate limitation. BMC Biotechnology, 11, (2011), 22-33.
3. Nienow, AW, Scale-Up, Stirred Tank Reactors. In: Encyclopedia of Industrial Biotechnology, John Wiley &
Sons, Inc., Hoboken, NJ, USA, DOI: 10.1002/9780470054581.eib535: Vol. 7 (2010) 4328 - 4341.
4. Nienow, AW, Aeration-Biotechnology, In: Kirk Othmer Encyclopedia of Chemical Technology, 5th Edition,
Wiley, New York, USA, 2003.
5. Denkov, ND, Mechanisms of Foam Destruction by Oil-Based Antifoams, Langmuir, 20, (2004), 94639505.
6. Boon, LA, Hoeks, FWJMM, van der Lans, RGJM, Bujalski, W, Wolff, MO and Nienow, AW, Comparing a
Range of Impellers for Stirring as Foam Disruption (SAFD), Biochem. Eng. J., 10, (2002), 183-195.

Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

Nomenclature
AH, heat transfer area
AT, cross-sectional area of the fermenter
AR, aspect ratio, H/T
B, baffle width
C, bottom impeller clearance above vessel base
D, agitator diameter
H, bioreactor fill level
kLa, specific mass transfer coefficient
M, mass of broth in the fermenter
N, agitator speed
OTR, oxygen transfer rate from the gas phase
OUR, oxygen uptake rate by the cells
P, power
QG, volumetric gas flow rate
QH, metabolic heat evolution rate
Re, Reynolds number (= ND2/)
RQ, respiratory quotient
T, bioreactor diameter
U, overall heat transfer coefficient
vS, superficial gas velocity
vvm, specific volumetric air flow rate

Greek Letters
a, b, exponents
CL, driving force
C, spacing between impellers with dual or more impellers
u, temperature driving force
T , local specific energy dissipation rate
T , mean specific energy dissipation rate
, viscosity
v, kinematic viscosity
, liquid density
um, mixing time

Subscripts
g when air is sparged

Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

Tables
Table 1 Bioprocess Specific Data (Nienow, 2010)
a) That Obtainable in Shaken Microtiter Plates or Shake Flasks
1 Media design
2 Metabolite concentrations including product inhibition*
3 Feeding algorithm for fed batch*
4 Choice of pH control agents and sensitivity to pH*
5 Temperature sensitivity*
6 Growth and production patterns *
7 Oxygen-demand, CO2 production and RQ profile *
8 Heat-release rate (probably estimated well enough from OUR) *
9 Substrate utilization efficiencies *
10 Cell and product concentrations *
11 dO2, pCO2 and osmolality tolerance*
* The main problem is the measurement and control of pH, dO2, pCO2 and cell mass at these scales.
b) That Obtainable from Batch/Fed-Batch Bench Scale Stirred Bioreactors
12 kLa profile ( including impact of antifoam)
13 Foaming/hold-up characteristics
14 Sensitivity to fluid dynamic generated stresses from agitation or bubbling aeration
15 Stresses associated with spatial broth inhomogeneity on scale-up

Table 2 Generic Physical Parameters Required for Design/Scale-up (Nienow, 2010)

a) Parameters most essential for scale-up/design
1 Adequate rate of mass transfer (O2 in, CO2 out)*
2 Bubble hold-up*
3 Satisfactory heat transfer for temperature control*
4 Impeller power number, Po, and unaerated motor power draw, P = PoN3D5
5 Mean specific energy dissipation rate, T = P/M W kg-1
6 Reduced power draw on aeration, Pg ((T)g = Pg/ M)
7 Good air dispersion
8 Effective bulk fluid mixing
* These values will be specific to each bioprocess
b) Parameters which aid understanding
9 Flow close to the agitator single - and two phase air-liquid
10 Spatial variation in local specific energy dissipation rates, T W kg-1
11 Gas phase mixing

Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

Figures

Figure 1a. Schematic representation of multiple Rushton impellers in fermenters (D/T =1/3; B/T =1/10; C/T = 1/4; H/T = ~ 3; 4 baffles)

Alvin W. Nienow

Merrick Consultancy

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

Fig 1b A photo taken during the installation of wide blade bydrofoil impellers in a fermenter.

Alvin W. Nienow

Merrick Consultancy

10

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

a) Shaken micro-titer plate

b) Multiple shake flasks

Alvin W. Nienow

Merrick Consultancy

11

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

c) Bench scale fermenter

d) Pilot scale fermenter

Fig 2 Examples of the range of scales used to establish the required commercial operating conditions.

Alvin W. Nienow

Merrick Consultancy

12

Stirred Bioreactor Engineering for Production Scale, Low Viscosity Aerobic Fermentations: Part 1.

Wide blade
hydrofoil

Cooling
Jacket

Hollow blade
impeller
a)

Baffles which
may also be
used for
cooling

Cooling coil

b)
Fig 3 Cooling surface area provided by a) a jacket; b) coils

Alvin W. Nienow

Merrick Consultancy

13