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Hydrodynamics of Stirred Bioreactors

Article in Applied Mechanics Reviews January 1998

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 Hydrodynamics of stirred bioreactors

AW Nienow
BBSRC Centre for Biochemical Engineering, School of Chemical Engineering,
University of Birmingham, B15 2TT, UK

This r e v i e w o f the h y d r o d y n a m i c s o f stirred bioreactors begins with an introduction to the agita-

tion p r o b l e m s o f particular concern in such systems. This is f o l l o w e d by a b r i e f r e v i e w o f s o m e
basic c o n c e p t s in turbulence and r h e o l o g y o f relevance to bioreactors. Important aspects o f single
phase m i x i n g in low viscosity, high viscosity and rheologically c o m p l e x broths are then c o v e r e d
in s o m e detail including flow patterns, p o w e r n u m b e r versus R e y n o l d s n u m b e r p l o t s (including
the modification o f the latter to allow for shear thinning broths), f l o w numbers, energy dissipation
rates and f l o w close to impellers and between multiple impeller systems. F r o m these basic princi-
ples, the p r o b l e m o f h o m o g e n i z a t i o n is then c o v e r e d in depth because o f its significance for
bioreactor performance. Aeration concepts are then introduced and the b e h a v i o r o f traditional
Rushton turbine impellers is then'treated in detail, c o v e r i n g the f l o w patterns, aerated p o w e r
characteristics, m i x i n g time and scale-up considerations. The weaknesses o f the Rushton turbine
are then discussed which leads into a section describing h o w m o r e m o d e m impellers are able to
i m p r o v e on m a n y o f these, especially emphasising their ability to introduce m o r e energy dissipa-
tion into the broth and handle m o r e air before flooding, both o f which enhance o x y g e n transfer.
The i m p r o v e m e n t in bulk blending found with multiple axial f l o w agitators is brought out too.
Finally, the retrofitting o f fermenters originally containing Rushton turbines with these m o r e
m o d e m impellers is discussed. In conclusion, it is clear that there have been substantial increases
in the understanding o f stirred bioreactor hydrodynamics. H o w e v e r , whilst further understanding
will o c c u r within the f r a m e w o r k discussed here, the expectation must be that computational fluid
d y n a m i c s will increase in importance in spite o f the difficulty o f handling c o m p l e x rheology,
multiphase systems and biological responses. This r e v i e w article has 135 references.

CONTENTS Theory .................................................................................15

LIST OF SYMBOLS ........................................................................ 4
INTRODUCTION ............................................................................ 4
BASIC ASPECTS OF TURBULENCE AND RHEOLOGY ........... 6
Rheological properties ................................................................ 7
Newtonian fluids - viscosity ................................................. 7
Non-Newtonian fluids: shear stress-shear
Rate relationships ........................................................... 7
Viscoelastic effects ............................................................... 8
Turbulence .................................................................................. 9
Kolmogoroffs theory of local homogeneous isotropic
turbulence: The eddy spectrum ............................................ 9
BASIC PARAMETERS OF AGITATION
WITHOUT AERATION .......................................................... 10
Introduction .............................................................................. 10
Reynolds numbers and flow patterns in Newtonian fluids ....... I 1
Power number - Reynolds number plots .................................. 11
Shear stress-shear rate from impeller rheometers ............... 13
Flow patterns in non-Newtonian fluids .................................... 13
Flow numbers ........................................................................... 13
Turbulence intensity and local energy dissipation rates ........... 14
Flow close to and behind impeller blades ................................ 15
Multiple impellers .................................................................... 15
MIXING~HOMOGENIZATIONOF THE
BROTH WITHOUT AERATION ................. i.......................... 15
Turbulent flow with a single impeller ...................................... 15
Experimental results ............................................................ 17
Transitional flow ....................................................................... 18
Yield stress fluids ...................................................................... 18
Multiple impeller systems .............. ~.......................................... 18
AERATION CONSIDERATIONS ................................................. 19
BASIC PARAMETERS OF AGITATION
WITH AERATED RUSHTON TURBINES ............................. 19
Bulk flow patterns ..................................................................... 19
Low viscosity broths ........................................................... 19
Effect of increasing viscosity .............................................. 20
Hydrodynamics local to the agitator ......................................... 20
Low viscosity systems ........................................................ 20
High viscosity, shear thinning broths .................................. 21
Power drawn ........................... .................................................. 21
Low viscosity broths ........................................................... 21
High viscosity broths .......................................................... 22
Mixing time ....... ....................................................................... 22
Scale-up .................................................................................... 23
Single turbines .................................................................... 23
Multiple turbines ................................................................. 23
Effect of depth and back pressure ....................................... 23
High viscosity broths .......................................................... 23
AERATED MIXING WITH OTHER AGITATORS...................... 23
Possible improvements on Rushton turbines ............................ 23
Power draw ......................................................................... 23

part of FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY,edited by R Pohorecki

ASME Reprint No AMR233 $70
Appl Mech Rev vol 51, no 1, January 1998 3 1998 American Society of Mechanical Engineers

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 4 SPECIALISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

Flooding .............................................................................. 24 k eddy length scale m

Improved bulk blending ...................................................... 24 ~r Kolmogoroff length scale m
Enhanced gas-liquid mass transfer ...................................... 24 apparent viscosity N s m -2
Pa
Heat transfer ........................................................................ 24 N s m -2
la dynamic viscosity
Lower shear rates ................................................................ 24 2-1
V kinematic viscosity ms
Other radial flow agitators ........................................................ 24
1st normal stress difference Nm "2
Rushton turbines with extra blades ..................................... 24 VI
-3
Hollow blade Rushton turbine ............................................ 25 P liquid density kg m
ICI Gasfoil ........................................................................... 25 shear Stress N m -2
Scaba 6SRGT ...................................................................... 25 N m -2
~y yield stress
Axial flow impellers: downward pumping= .............................. 25
0m mixing time S
Pitched blade turbines ......................................................... 25
O0 rotational speed rad/s
Hydrofoil agitators .............................................................. 26
Axial flow agitators: upward pumping ..................................... 27
Ekato lnterrnigs ......................................................................... 27 Superscripts
Two independently driven agitators .......................................... 28 ' fluctuating
RETROFITTING ............................................................................ 28 mean
CONCLUSION ............................................................................... 29
ACKNOWLEDGEMENT ............................................................... 29 Subscripts
REFERENCES ................................................................................. 29
CD complete dispersion
C Casson parameters (Eq (5))
L I S T OF SYMBOLS E exchange flow rate
Ai,A2 correlation constants F flooded
B baffle width m g gassed
C impeller clearance off the base m GV based on vvm
AC distance between impellers m HB Herschel-Bulkley parameters(see Eq (4))
D agitator diameter m i instantaneous
0~ sparger diameter m max maximum energy dissipation rate
F! flow number r ratio of the energy dissipation rate at the wall,
FIG gas flow (or aeration) number compared to the mean, ie, ( ~ T ) T / ( ~ T )
Fr Froude number R recirculation
H Liquid height m
rms root mean square
1 intensity of turbulence (see Eq (9)) T energy dissipation rate at the wall
K consistency index N snm"2
gl impeller constant (=PoRe)
2 -2 INTRODUCTION
kT kinetic energy of turbulence/unit mass m s
shear rate constant Until recently, most industrial-scale bioreactors were agitated
Lc integral scale of turbulence m by a set of Rushton turbines (Fig 1), named in recognition of
M agitator torque Nm the extensive research on mixing and agitators by JH Rushton
n flow behavior index and co-workers in the 1950s.
-I
N agitator speed s
These workers suggested that a few standard agitator de-
P agitator power W
signs could meet the requirements of most situations and rec-
Po power number
Q volumetric flow rate
3-1
ms
ommended the Rushton turbine specifically for its gas disper-
Re impeller Reynolds number sion characteristics - these turbines are about 1/3 of the fer-
Rek Kolmogoroff scale Reynolds number (Eq (11)) menter diameter, with the disc forcing air into the high shear
T tank diameter m region of the fiat blades, where break-up of the bubbles oc-
-I
II velocity ms curs. Their recommendation, combined with the engineering
Ur, VF, W t fluctuating velocity in the x, y and z expertise of the manufacturers Lightnin', with whom Rushton
-1 was associated, led to the widespread use of the Rushton tur-
direction respectively ms
v~ eddy vdocity ms
-1 bines.
superficial gas velocity ms
-I Occasionally in earlier work, and especially for more vis-
V liquid volume m
3 cous fermentations such as Xanthan, an angled blade agitator
x,y,g distance (direction) m (45-pitch) (Fig 2) was suggested as the upper agitator be-
cause of its claimed higher pumping capacity (Solomon et al,
Greek 1981a). Also, for high viscosity broths, the use of two inde-
Gt exponent
pendently-driven agitators has also been proposed by RHM
~A aspect ratio
Ltd (Fig 3), one for each of the above mentioned functions of
~g agitation, ie, the lower to cause air break-up to give a high
surface area of contact between air and broth and the upper
~T local specific energy dissipation rate m2s-3 to give movement throughout the vessel in order to avoid
2-3 dead zones (Anderson et al, 1982). Recently, an interest in
gT mean specific energy dissipation rate (= P/pV) ms

shear rate s-I

using high flow number, low power number agitators such as
the Ekato Intermig (Fig 4) (which are always used two or

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 Appl Mech Rev vo151, no 1, January 1998 Nienow: Hydrodynamics of stirred bioreactors 5

more at a time), or the Lightnin A315 (Fig 5b) and the Table I. Stirred bioreactor parameters that are
Prochem Maxflo T (Fig 5c) has developed, especially for ret- not biological system specific
rofitting extant fermenters (Buckland et al, 1988, Balmer et
a/, 1987). The radial flow Scaba 6SRGT and Chemineer Fluid dynamics
CD6 also look promising (Fig 5a and d). The reasons for the /) Macro-aspects
interest in these other vessel/impeller systems will be made ii) Local to the agitator
clear as this article develops. iii) Local specific energy dissipation rates
Bulk fluid and gas phase mixing
In addition to the air from the sparger being broken up,
Power drawn
the elimination of dead zones which could become anaerobic
Air dispersion capability
and the need to provide good bulk mixing, the agitator assists Oxygen mass transfer coefficient
Heat transfer
Motor G~r box
8/T = 0"1 mass transfer from air bubbles to broth and from broth to mi-
croorganisms; and heat transfer between broth and coils
H/T = 3 " 3 and/or jackets. The level of agitation must be sufficient to
O/T = 0"35 achieve satisfactory rates for all of these processes. One or
other of them will usually be the most demanding on the
C/T = 0"25 mixing and which will depend, inter alia, on the rheological
properties of the broths, the scale of operation and the oxy-
~C/T : 0"51 gen demand of the microorganism and its sensitivity to dam-
age. Inevitably heat transfer becomes more difficult in large
fermenters because heat flux scales with volume whilst heat
removal scales with area; and for geometrical similarity,
area/volume is inversely proportional to scale. The difficulty
with large scale heat transfer
is another reason for the ge- _ _ r---'7
ometry proposed by RHM
(Fig 3) where the draft tube
provides additional cooling
area. o
Rushfon Turbine Overall performance then
is determined by the interac-
tion of two sets of parame- o ~ .~ o
ters (Nienow, 1990a). First- ~ o o
ly, System-independent phy- Ai ?1 ! o o
sical parameters, as dis- o io
cussed above and summa- o . ~o
rized in Table 1, all of which | | o
MIXIN6 EQUIPMENTC0.-1981
are related to the hydrody- ~ '~' ~ o
Fig 1. Geometry of a large fermenter agitated by Rushton turbines. namics. Secondly, there are
Relative dimensions of the different components compared with System-dependent biological o
fermenter vessel diameter (T) are: B/T = 0.1; H/T - 3.3; D/T -
parameters related to bio-
0.35; C/T = 0.25; A C/T = 0.51, (Nienow, 1990a). o o
logical performance (Table
2) and, though dependent on i
Boffles N non-specific aspects of agi-
Of 90* -j
0.1 tation (Table 3), can only
really be studied on the bio- N 'l . d
_L reaction of interest. System- H ]'~',,..O.nrO. . J "
specific features relate to the
sensitivity of the bio-reaction
,,,0 to factors such as high and
I! low levels of dissolved oxy-
- 3
'r
gen and nutrients (especially Fig 3. A fermenter with inde-
,r'~-I ,\ \i I
in fed-batch operations), and pendently-driven agitators; an
pH. For all these parameters axial flow hydrofoil for bulk
deviations from the mean flow and a Rushton turbine for
IP, = O:t,T
concentration defined in air dispersion, as proposed for
T small laboratory experiments very large scale, high viscosity
gas-liquid systems. (Anderson et
Fig 2. A 45 -pitch, angled-blade impeller. al, 1982).

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 SPECIAL ISSUE: FLUID MECHANICS PROBLEMS IN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

Table 2. Biological performance parameters one (Metz et al, 1981). This change is often beneficial due to
which are system specific the very big drop in viscosity leading to higher rates of oxy-
gen transfer from air to broth. However, the pellets must not
Growth and product secretion
be so large that they are starved of oxygen at their core
Damage to micro-organisms
Morphology changes (Nienow, 1991).
Nutrient demand including 02 This review concentrates on providing an in-depth analy-
sis and understanding of the physical parameters and gives a
02 and CO2 transfer rates
few examples of where changes following such understand-
are likely to increase due to poor mixing with increasing size ing has led to improved biological
of fermenter (Sweere et al, 1986), especially with broths of performance. r

increasingly shear-thinning behavior during the progress of a

batch or fed-batch fermentation such as those arising from
BASIC ASPECTS OF
filamentous (Metz et al, 1981) or polysaccharide (Nienow,
TURBULENCE
1984) fermentations. Mechanical stress may also cause dam-
AND R H E O L O G Y
age, but it is not easy to isolate mechanical aspects from nu-
trient effects, especially dissolved oxygen (Van Suidam and In order to gain an understanding
Metz, 1981). of bioreactor fluid dynamics, it is
Thus, even if the non-specific parameters are well enough helpful to consider certain more b
understood, and a stirred bioreactor system that is more suit- fundamental concepts. In most
able for one type of application than another can be selected, bioreactors, the bulk flow is tur-
it must eventually be tested with respect to biological per- bulent and therefore some of the
formance. However, without a good under-standing of the concepts of turbulence are intro-
parameters in Table 1 at different scales, with broths of dif- duced. In practice, the major pa- C

ferent rheological properties, and with different agitators, rameter which determines
there is little chance of linking mixing parameters to biologi- whether the flow is turbulent or
cal performance. laminar is the viscosity of the
A further complication arises with mycelial fermentations. fluid. However, viscosity as a
There is a very complicated feedback loop involving rheo- constant value and as a property
logical properties, morphology, mixing and transfer proc- that is capable of describing on its
esses (Fig 6) (Van Suidam and Dusseljee, 1987). Indeed, un- own the likely flow behavior of
der a certain combination of circumstances, the highly vis- that fluid is essentially restricted d
cous mycelial growth form may be transformed to the pelletal to a few, pure, single phase, gen-
erally low molecular weight flu-
ids. Most fermentations consist of
t,. Bcxfftes
at least three-phase systems often
with structure, the latter arising Fig 5. A selection of mod-
from either the presence of the em impellers: a) Scaba
F growing organism (filamentous 6SRGT, b) Lightnin A315,
fermentations) or the product c) Prochem Maxflow T, d)
(exocellular gums). Thus, ideally, Chemineer CD6.

PROCESSCONDITIONS
temperature, pH, osmotic pressure, shear,
medium tomposition 1
he two ctgitotors
I I are set Qt 90*
I I to ~ach other
1/10r 07: i Microbial ~ Product L~.I G,uwf.--"
"-
, I I 0-6T ~1 morphology ~ formation ] I

I
I Apparent
I
morphology~ Broth
rheology i.....

~ . ~ Ring sparger JMass

transfer I Mixing J Heat
transfer J
T
[ I
I Recommendedpumpingdirection
Fig 6. Representation of the relationship between morphology,
Fig 4. A pair of Ekato Intermig agitators for gas dispersion (appro- broth rheology and process conditions (van Suidam and Dusseljee,
ximately to scale (Nienow and Ulbrecht, 1985)). 1987).

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 Appl Mech Rev vol 51, no 1, January 1998 Nienow: Hydrodynamics of stirred bioreactors 7

Table 3. Main linkages between Tables 1 and 2 with flows which are not chara&erised by good approxima-
tions to idealised ones, generally do not give accurate and
Quality of homogenization
meaningful viscosity
Oxygen toxicity rotate inner cylinder;
Oxygen starvation values. Thus, the Brook- measuretorque
CO2 concentrations field viscometer, which for flow curve
pH excursions is frequently used in the 4)
Nutrient excursions bioindustries, with its
"Shear" damage bob in an infinite fluid
Stress from fluid dynamics and from does not have a well
region of shear
bubble/cell interactions characterised shear field
and therefore does not
a full description of their rheological properties should be give the correct quanti-
available because they all have an effect on one or more of tative data. Even the
the parameters set out in Table 1. However, their measure- idealised geometries of stationary outer
ment is not often easy and a full set is rarely obtained. Fig 8 can give mean- 'l---cylinder
ingless results if, for ex-
Rheological properties
ample, secondary flows
In order to appreciate the physical significance of the most (Taylor vortices) de- J:: J:
\
important rheological properties, it is quite helpful to con- velop, superimposed on air pocket
sider certain idealised flows. Equipment which is used to the shear flow. These (a)
measure these properties produces such flows or something are illustrated in Fig 9 rotate cone; measuretorque
approximating to them. There are many books available for a concentric cylinder for flow curve.
which deal with this tropic in some detail, eg, Barnes et al device (Sinovic et al, -~ measurenormal
(1989). All that is presented here is sufficient to allow the ~ force for
1986). viscoelasticity
reader to understand this article better.
Non-Newtonian Fluids:
Newtonian Fluids - Viscosity Shear Stress-Shear Rate
For fluids undergoing laminar shear as illustrated in Fig 7, Relationships
the resistance to deformation depends on the dynamic vis- For most biological flu-
cosity. For a linear velocity gradient arising due to the ids, the viscosity is a
movement of one parallel plate over another, the relationship function of shear rate.
between shear rate, ~,, and shear stress, x, is given by This is generally the
x = ~tdu / dy = ~t~ (1) case when a fluid con- ~.~.._ ~,..7.7"~ ~ region of
tains large complex mo- fluid I shear
where, for Newtonian fluids, the viscosity la is constant, in-
lecules in solution, such
dependent of shear rate, ~. Water has a viscosity o f ~ l mPas
as polymers; or morpho-
(1 cps) and fermentation media and broths containing simple logically-complex bio- stationary
cells in suspension will generally remain Newtonian with vis- mass in suspension. plate
cosities not much greater than water except at high concen- Since the range of shear (b)
trations. Animal cell culture fluids are also not very different Fig 8. Two rotational viscometers a)
rates in a bioreactor
concentric cylinder, b) cone and
from water. varies considerably with plate.
To determine the relationship between shear stress and
shear rate, a range of viscometers is available. Two of them
~_.=...~ ~ ~__L._..~~
(Fig 8) try to simulate the ideal flow represented by parallel
plates; one has con-
centric cylinders (Fig R2
8a) and the other, a
cone and plate confl-
Ay guration (Fig 8b). 1
Another simple con-

_.Y figuration is the cap-

illary viscometer. Full
details and the ad-
vantages and disad-
Au
vantages of the vari-
z~u ous types are given in
velocity gradient, - - the books referred to
Ay Fig 9. Taylor vortices in a concentric cylinder viscometer (Taylor
above. More impor-
= s h e a r r a t e , '7 tantly, rheometers
numbers, Ta,< 43 must be used where Ta = p e R I 14d/Rl)/l.t
Fig 7. Laminar shear flow and shear rate. to give meaningful viscosity values).

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 8 SPECIAL
ISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY
agitator type and from place-to-place within it, shear stress-
shear rate data over a wide range of ~ are required.
Data from viscometric experiments are given normally in
the form of a flow curve, a plot o f x against '~. Apart from
Newtonian fluids, two other categories are important in bio-
reactors, as indicated in Fig 10. These categories and their
implications for bioreactors may be classified as follows:
Pseudoplastic or shear thinning. This property is exhib-
ited by an extremely wide range of broths. An apparent vis-
cosity, it,, is defined as
~. = ~/./, (2)
and, with this type of fluid, viscosity decreases with increas-
ing shear rate. Thus, the viscosity tends to be low close to the
impeller even though it is high elsewhere. In this case, good
mixing may occur in the impeller region with near-stagnant
regions in the remainder of the vessel.
Plastic. Such materials are characterised by a yield stress,
xy. This is found particularly with the highest viscosity poly-
saccharide broths, eg, Xanthan (Galindo et al, 1988) or fila-
mentous fermentations, eg, Aspergillus foetidus (Baker et al,
1988) where a minimum stress is required to break down the
structure sufficiently before any movement will occur. In this
case, the well-mixed region close to the impeller, which has
been called a cavern, may be accompanied by a broth which
elsewhere is only moved, if at all, by the sparged air.
Plots of viscosity versus shear rate for both such fluids are
shown in Fig 11 Values of Ty of 4 Pa were quoted for 16. I g
dry wt/litre Aspergillus (Baker et ai, 1988) and 10 Pa for
10g/litre Xanthan gum (Galindo et al, 1988).
It is often convenient to express flow curves (ie, experi-
mental data relating shear stress to shear rate) in algebraic
form. The power law model is the most commonly used
x = K~" (3)
where K is the consistency index and n the flow behavior in-
dex. Almost all broth flow curves can be fitted quite well by
such an equation over a limited range of shear rates but it is
dangerous to extrapolate outside the range of measurements.
If n < 1, the fluid is shear thinning; if n = 1, it is Newtonian
and K = It.
shear rate. ~
Fig I O. Examples of flow curves on linear co-ordinates of different
types of rheological behavior of importance to bioreactors.
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Appl Mech Rev vol 51, no 1, January 1998
For plastic fluids which have a yield stress, one simple
relationship which is commonly used is the Herschel-Bulkely
equation:
x = xy + K n ~ " M 8 (4)
where ~y is the yield stress. Another is the Casson Equation
~0.5 = ~y0"5+ Kc~0.5 (5)
which has been found to be a good fit to the data from a wide
range of fermentation broths (Baker et al, 1988).
It is important to realise that the yield stress, Xy is ex-
tremely difficult to determine unequivocally. The flow curve
of a highly shear thinning fluid on linear co-ordinates very
often indicates a finite yield stress. However, this may be due
to the bunching of the data at low shear rates. Extending the
low shear rate range graphically on log-log paper often sug-
gests that the power law alone is sufficient. This problem is
discussed further under the Section on homogenization of
such broths.
Other problems arise when measuring the flow curve of
solid suspensions such as filamentous fermentations. Essen-
tially, the solid phase tends to concentrate and migrate within
the rheometer's gap or perhaps actually fill it, depending on
their respective sizes (Metz et al, 1979). In this case, a
method can be used which was first proposed by Bongenaar
et al (1973) and recently extended by Baker (1988). It is
based on the use of a turbine agitator in the laminar f l o w re-
gion as a rheometer. It is covered later in the Section on av-
erage shear rates as defined by Metzner and Otto (1957) for
agitated shear thinning fluids.
Viscoelastic effects
If the structure of the fluid is sufficiently complex and con-
tains very large polymeric molecules, this structure may
cause the fluid to behave in part as a viscous liquid and in
part as an elastic solid, ie, they can exhibit elastic recovery.
Such fluids are called viscoelastic. Typical manifestations of
viscoelasticity are:
i) When sheared in a cone and plate device, large
normal forces as well as large shear forces may be developed
in viscoelastic liquids (see Fig 8b) (often expressed as 1st
normal stress difference, v 0. When such fluids are agitated
by rotating stirrers, the fluid will often climb up the shaft due
~'- I
g.
I0-2 I I I =
O" 1 10 100 100
S h e a r rate. p
Fig 11. Examples of viscosity versus shear rate (log-log plot).
 Appl Mech Rev vol 51, no 1, January 1998 Nienow: Hydrodynamics of stirred bioreactors 9

to the Weissenberg effect (Elson et al, ~OC

volume conserved: decreasing thickness, increasing area
1982). However, the lack of shaft climb- ~streamli.nes
ing does not mean that the fluid is not nvergmg
viscoelastic, especially if it has a yield
stress (Elson et al, 1982).
ii) They exhibit typical relaxation
[ 1,
times. If they are subjected to slow dis-
tortion they behave like a fluid; i f a rapid
one, like a solid. A good everyday ex- Fig 12. Extensional flow and elongation rate.
ample is silly putty.
iii) Associated with most shear flows, there are elonga- For isotropic turbulence, the deviations in each direction are
tionai flows as indicated by Fig 12. They particularly occur the same, so that
in the flow off agitator blades and in bubble eruptions. In this
case, the fluid's resistance to deformation depends on its I = - u'ms (9)
elongational viscosity. For Newtonian fluids, the elongational U U

viscosity is three times the shear viscosity. This is known as Turbulent flow also gives rise to turbulent Reynolds shear
Trouton's rule. However, for non-Newtonian fluids, espe- stresses due to the interaction between velocity fluctuations
cially highly viscoelastic ones, the ratio can be two orders of in different directions, ie, - p u ' v ' . This product relates to the
magnitude or more greater than this. Little has been pub- transfer of momentum due to turbulence, just as viscosity
lished yet on the role of elongational viscosity in bioreactors transfers momentum due to velocity gradients in laminar
and its measurement is very difficult. The reader is referred
flow. There are two other turbulent shear stresses - p u ' w '
to the book by Waiters (1975) and the review article by
Cheng (1979). and - p v ' w ' and 3 normal stresses, pu-72 pv-~2 and pw -'72
All these manifestations of viscoelasticity give rise to By a suitable treatment of the data from a hot film or laser
poorer mixing and bubble stabilization, ie, larger bubbles are Doppler anemometer, micro and macro scales of turbulence
found in viscoelastic broths such as Xanthan. Both these ef- as well as local energy dissipation rates can be obtained.
fects can give rise to difficulties in mixing in fermenters as Values for these parameters in stirred bioreactors are pre-
discussed below. sented later.
Turbulence Kolmogoroff's theory o f local homogeneous
Turbulence in fluids is characterised by three~dimensional isotropic turbulence: The eddy spectrum
random fluctuations in velocity as observed at a single point The complexity of the turbulent flow in bioreactors which is
(whether fixed in space or moving with the fluid). This is the usually fully three-dimensional, makes an analysis extremely
case in most bioreactors with respect to the bulk flow. How- difficult. However, provided the Reynolds number of the
ever, most of the theory that has been developed applies to main flow is high enough, Kolmogoroff's theory of local
single phase, Newtonian, low viscosity fluids. Measurement homogeneous isotropic turbulence can be used to give some
is typically done by a hot film or a laser Doppler anemome- insight into its structure (Levich, 1962) and has therefore
ter. Both are difficult to use in aerated systems and the for- been used extensively for the analysis of stirred reactor
mer in non-Newtonian fluids. Here, only some of the impor- problems. Turbulent motion can be considered as a superpo-
tant concepts are presented and for further information refer- sition of a spectrum of velocity fluctuations and eddy sizes
ence should be made to specialist books, eg, Brodkey (1975). on an overall mean flow. The large primary eddies have large
It is convenient to describe the motion in terms of its de- velocity fluctuations of low frequency and are of a size com-
viation from the time average values, so that parable with the physical dimension of the system, for exam-
ui = u + u' (6) ple, the impeller diameter D (see Fig 13). These eddies are
where anisotropic and contain the bulk of the kinetic energy. Inter-
t action of the large eddies with slow-moving streams pro-
u = 1 / tfo uidt (7) duces smaller eddies of high frequency which further disinte-
in which t is large, with similar expressions for u and w in the
y and z direction. Turbulence is said to be homogeneous
when, at all points in the system, the same time averaged LARGE EDDIES INERTIAL VISCOUS
RANGE RANGE
fluctuations occur at all points. Turbulence at a point is said
to be isotropic when deviations are similar in all directions,
averaged in time and using a root mean square for the aver-
I
aging. The specific intensity of turbulence, /, is defined in I
I ISOTROPIC
terms of these variations such that, for the case when the iMPELLER ANISOTROPIE~= 0.1D i
1
~
mean flow u is in a defined direction, then BLADE
I
i DECAY
i
~1 / 3{u72 + -72
v + -'72
w } AK
I (8)
U
Fig 13. Kolmogoroff concept of a spectrum of eddy sizes.

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 t0 SPECIAL ISSUE: FLUID MECHANICS PROBLEMS IN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

grate until finally they are dissipated into heat by viscous 1000 s-1 at that scale.
forces. There is a transfer of kinetic energy down the scale
For the inertial sub-range, ~ > Lk, all parameters are inde-
from larger eddies to smaller eddies, the directional elements
pendent of viscosity, so again from dimensional reasoning,
of the main flow being progressively lost in the process.
Kolmogoroff argued that, for large Reynolds numbers in = = ( Tz)"3 (l s)
any flow system, the smaller eddies are independent of the and the shear rate
bulk motion and are locally homogeneous and isotropic.
Therefore, the properties of these eddies are firstly a function
: vU>, : ) (16)
of the local energy dissipation rate/unit mass, ~T- Below the For the viscous subrange, ~k > 3,
eddy size, Zk, at which viscous dissipation occurs (the Kol- = s ( , , , v , Z ) = z ( , , / v ) ''2 (17)
mogoroff length scale), their properties also depend on vis- and the shear rate
cosity. There is therefore an equilibrium established which
contains a very wide range of eddy sizes, the universal equi- (18)
librium range. With the larger of these eddics(D >> L >> Lk), By implication, processes which are particularly depend-
energy passes from bigger to smaller without dissipation. ent on turbulent eddies and their associated forces are likely
This is the inertial sub-range, ie, L >Zk. The sizes below Zk to be well correlated by energy dissipation rate. Gas-liquid
over which viscous dissipation occurs is the viscous sub- mass transfer rates and hold-up fall into that category. How-
range. Figure 14 shows this structure. An eddy Reynolds ever, processes which are dependent on the anisotropic main
number, Rek, is now defined for the Koimogoroff length flows and for which the non-homogeneous nature of stirred
scale as tanks turbulence is significant, eg, the flow rate of air which
an impeller can disperse, are not well correlated that way.
Rek = ~ k v k / v (10)
Conceptually the Reynolds number represents the balance of
BASIC FLUID DYNAMIC PARAMETERS
inertial to viscous forces; and within thespectrum of sizes the
OF AGITATION WITHOUT AERATION
Kolmogoroff scale is the size where these two forces are in
balance. Therefore, it is convenient to quantify eddy Rey- Introduction
nolds numbers in general in relation to Rek by the definition Initially, the flow in an agitated bioreactor under unaerated
Re~ = 1 (1 l) conditions will be considered since many of the basic con-
cepts are also applicable to the aerated case. In addition, an
From dimensional reasoning, the Kolmogoroff length scale is
appreciation of the unaerated case is necessary if the aerated
defined as
one is to be better understood. If the power levels required
x, =/(v,~r) = (v3/~,) ''4 (12) for a successful bioreactor operation are applied, the agitator
speed is such that, in a plain cylindrical vessel, a predomi-
and the velocity scale vk associated with it is nantly swirling flow and accompanying vortex is produced
1"k = f ( v , I ~ T ) = ( V I ~ T ) TM (13) which it is necessary to prevent. With the vortex present,
and the shear rate vertical flow is almost negligible so that mixing is very poor
between top and bottom; and. the power level is almost im-
= = (14) possible to predict and maintain. Thus, almost all bioreactors
For an energy dissipation rate of I W/kg (hHP/1000 US gal- from laboratory to industrial scale are fitted with 4 vertical
lons) in water, Eq (l 2) gives Xk = 30 p.m with a shear rate of strip baffles as shown in Fig 1 which effectively prevent
most energetlc
eddies

l anisotropic
iso!rop~c
independent of 6 Blades
type of impeller

(a)
function of impeller type
\
q
length scale, Xk
eT = area under the curve
XXolmogoroff
;io'C;:n'ge
inertial \ I I/ Cl H < ~5

largest eddies smallest (b)

of order D eddies
1/;tT Fig 15. Flow patterns in unaerated flow with a radial flow Rushton
Fig 14. Spectrum of eddy sizes and their energy in turbulent flow. turbine; a) at high clearance, C/T> ~ 1/5; b) at low clearance, C/T<
~ 1/5.

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 Appl Mech Rev vol 51, no 1, January 1998 Nienow: Hydrodynamicsof stirred bioreactors 11
vortexing. Even at the low agitation speeds and power input pattern as indicated in Fig 15a, at all C/T> ~ 1/5. At C/T<
required for animal cell culture, such baffling helps homog- 1/5, the flow with a Rushton dips towards the base (Fig 15b)
enization and does not cause mechanical damage to cells as (Nienow, 1968) and it is probable that the same effect is
discussed later. found with the others. As the viscosity increases and the
Given this baffling, the primary rotational flow of single Reynolds number falls, the flow pattern remains broadly the
impellers is damped to give strong secondary flows. These same for each clearance.
flows can be considered as either radial flow as with the With the axial flow hydrofoils, the most common flow is
Rushton turbine (Fig 1), the Scaba 6SRGT (Fig 5a) or the indicated by Fig 16 which shows a slight diversion from the
Chemineer CD6 (Fig 5d); or axial flow as with the down- true axial direction (Jaworski and Nienow, 1994). The small
ward-pumping hydrofoils, eg, the Lightnin A315 or Prochem region of flow reversal directly beneath the impeller is note-
Maxflo T (Fig 5c). The 45-pitched, blade turbine (Fig 2) worthy with respect to air dispersion (see Section on Aerated
and the Ekato Intermig (Fig 4) can be considered mixed flow Mixing). As the impeller is lowered to C/T < ~ 1/5, the flow
impellers in that the flow is neither radial nor even approxi- is constrained and forced outwards so that the region of flow
mately axial. reversal increases. With increasing viscosity and reducing
Reynolds number, this tendency to produce radial flow pro-
Reynolds numbers and flow patterns in Newtonian fluids gressively increases too so that when Re < ~ 150, A310 im-
The Reynolds number, Re, for stirred bioreactor is defined as pellers become radially discharging (Ibrahim and Nienow,
Re = pzND2 /i.t (19) 1995) as does an A315 (Weetman and Coyle, 1989).
Very similar effects are found with the mixed flow 45
where Re has its usual physical meaning, namely the ratio of
pitch turbine both with respect to the effect of C/T and in-
Re inertial to viscous forces. In stirred reactors, the flow is
creasing viscosity, though the region of flow reversal is
turbulent if Re > ~ 2 x 104 and laminar if Re < - 10 in New- greater (Jaworski et al, 1991). However, another feature is
tonian fluidS. Thus, unlike pipe flow, there is a very large that if the impeller is made so large that D/T > 0.5, the flow
transition region defined by 10 < Re < 2 x 104. Industrial becomes almost radial at all Re, especially at C/T > 1/3
bioreactors never operate in the laminar region because the (lbrahim and Nienow, 1995). With the Interrnigs, no well de-
broth does not become viscous enough. However, many fined flow direction is produced at Re > 2 x 104 but as Re
broths are sufficiently viscous to give transitional Reynolds falls, each becomes essentially a radial flow impeller at Re <
numbers. ~ 150 (lbrahim and Nienow, 1995).
In the fully turbulent region (Re > 2 x 104), the Rushton
turbine and the other radial flow impellers produce a flow Power number - Reynolds number plots
A group equivalent to the friction factor for pipes or a drag
coefficient for particles can be defined. It is the power num-
ber, Po, given by
Po = PIp LN3D5 (20)
VR Z where P is the power drawn by the agitator. To this, the
power required to allow for the motor efficiency and energy
I-I
losses in seals, gear boxes, etc, must be added in order to size
= . * * . . . . , , ! ~ * Zt 1
the actual motor. Some typical Po versus Re curves are given
0.2 ] f
in Fig 17 from data obtained in the mixing laboratories at the
0.0 University of Birmingham.
-0.2 j I To obtain such a plot, accurate power data are necessary,
..~.,,x,,.~,. \ I
utilising fluids having a wide range of viscosities. Electrical
techniques are generally unsatisfactory except on the largest
scale with variable speed motors. Noting from Fig 15 that in
the fully turbulent regime, ie, at Re > 2 x 104, Po = constant
for all the impellers, then
' / / ~ ' ~ [ z~ 10 ~ f PROCHEM
!-1/I " ,,I ~ _ ~ - ~ " " " ' ~ RUSHTON - 5.5

CMC C M r , ~ ~ '1.7

GLUCOSE WATER - 0.7

0. (0.35 EACIQ
INTERMIG
0*~ (PAIR)
0.~ BIRMINGHAM DATA

0.0 0.5 0.1 t I I~ . I

R=r/T t-1 10 10 2 10 3 10 4 10 5

Fig 16. Flow patterns in unaerated flow with downpumping hydro- Re

foils at Re > 2 x 104. Fig 17. Sometypical Po v Re data

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 12 SPECIAL ISSUE: FLUID MECHANICS PROBLEMS IN BIOTECHNOLOGY Appl Mech Rev vo151, no 1, January 1998

Po.N 3D 5 (21 ) where ks = 10-13 except for lntermigs where it is about 17

from Eq (20). In water, even at small scale except at exceed- (Dawson et al, 1993). If the shear thinning behavior is de-
ingly unrealistic low speeds, the flow is always turbulent. scribed by a power law relationship, ie,
Therefore, plotting experimental power date in water On = K i'n (3)
double logarithmic paper should give a slope of 3. This then a Reynolds number for such fluid can be defined as
check should always be carried out before power data from
electrical measurement are used (Nienow et al, 1994). In the Rea, = oND____~ (26)
laboratory, strain gauge-telemetry (Kuboi et al, 1983) is very ~ta
effective, especially for multiple impeller configurations where it,, is determined at ~ av from the flow curve (Fig 10);
(Hudcova et al, 1989), The technique can also be used in or as
fermenters by installing the gauge in a hollow shaft (Torres-
Re a = pLNE-'D2 (27)
tiana et al, 1991).
Kksn-I
The Rushton turbine has the highest P value in Fig 17 in
the turbulent region. Since power is also related to torque M It has also been found that the approachof Metzner and
by the relationship Otto works quite well as a means of estimating viscosity and
Reynolds number with shear thinning fluids in the transition
P = 2nNM (22)
region, ie, ~ 10 < Re < ~ 104 (Nienow et al, 1983). However,
then, for a given impeller,
if the fluid is also viscoelastic, as found in viscous polysac-
M = PopLN2DS/2~ (23) charide fermentations, P is further enhanced. For example,
Thus, the Rushton turbine is a high torque impeller in that Nienow et al (1983) found an ~ 30% increase with Rushton
for a given power and size, it requires a relatively low speed turbines as did Galindo and Nienow (1992) with A315s,
and a high torque. Low P agitators operating at the same whilst Ozcan-Taskin and Nienow (1992) found an increase of
power and diameter are operated at higher speeds and they a factor of 2 with Intermigs in Boger fluids (high viscosity
then require less torque and are cheaper to install requiring
fluids with a constant p and yet viscoelastic with v I et'~2 )
smaller diameter shafts, seals, gearboxes, etc.
When the flow becomes laminar, as in all such flows re- (Boger, 1977).
gardless of geometry, dimensionless groups like friction fac- Though it is probable that the manufacturers of impellers
tors are inversely proportional to Reynolds number, so that at have accurate P versus Re plots for a range of Reynolds
R e < 10, numbers and rheological parameters, the precise dependency
PoRe = K t (24) is not generally available in the open literature. Fig 18 shows
some data for Rushton turbines which gives some idea of the
where KI is a constant dependent on the impeller/vessel con-
complexity in the transitional region.
figuration as indicated above. Though industrial bioreactors
However, even in the turbulent region, the simple concept,
do not operate in this region, many fluids which are viscous
P = constant, does not completely hold (Bujalski et al,
enough to give Re < 10 are also, like fermentation broths,
1987). Thus, P is generally a weak function of the geomet-
shear thinning. Metzner and Otto (1957) showed that in these
rical parameters of the impeller, especially the material
fluids, a mean shear rate, YAv, can be used to estimate the
thickness, x. Thus, for a 45-pitch, 6-bladed turbine at C/T =
apparent viscosity in the laminar region, so that both viscous 1/4 (Bujalski et al, 1986) and D / T < 0.5,
Newtonian and shear thinning fluids can be accommodated
P = 0.78( D/r)-17 (4D)-0.14 (28)
within engineering accuracy by the same plot. For impellers
of the type used in fermentations, Surprisingly, for Rushton turbines, Po also depends on the
scale (Bujalski et al, 1987) so that at C/T= 1/4,
Y Av = k , N (25)
P = 2.5(x/D)-2 (T/To)65 (29)
I I I I I I
where To = lm. This use of To to make this Equation dimen-
....... } InehastiClSheor thinning
7 .............. ; Elostic J
sionless is clearly somewhat questionable but without a
physical explanation for this scale dependency, this approach
proved to be the best way of fitting the highly reproducible
/ ~ s S~ 'X a x x l X
data.
#_ P is also a function of impeller/vessel geometry, often
related to changes of flow pattern as set out above. For ex-
ample, at C/Tless than ~1/6 as the flow pattern for a Rushton
2 . __ Newtonian, turbine changes from the usual figure-of-eight to a single dis-
/ o T22 1
[ x T30 j~Fibres charge loop, so the P value drops by about 20% (Nienow
/ Tzz , Aspergittus and Miles, 1978).
l I I I [ I I With a 45-pitched blade turbine, as C/T is reduced, the
20 50 70 10 200 500 700 1000
Re more radial discharge and the restriction to the discharge
Fig 18. Some Po v Re data in the transitional Re region for the flow by the base causes P to increase as it does when D / T >
Rushton turbine (Nienow eta/, 1987).

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 Appl Mech Rev vo151, no 1, January 1998 Nienow: Hydrodynamicsof stirred bioreactors 13
0.5 and the flow tends to become radial with Po increasing liquid mixing and motion around the impeller, outside of
from about 1.7 to about 2.2 (Bujalski, 1987). A similar effect which the fluid is stagnant in dead zones or nearly so
of reduced clearance has been noted by McFarlane (1991) (Jaworski et al, 1994). In addition, there is no exchange of
with an A3 ! 5 where at C/T = 0.45, Po = 0.76 whilst at C/T = material (other than by diffusion) between the cavern and the
0.25, Po = 0.84; and by Ibrahim and Nienow (1994) for bulk (Solomon et al, 1981). For Rushton turbines, the cavern
HE3's and 310's. is usually cylindrical, centerd on the agitator and of height-
Po data for Re > 2 x 104 from the recent literature and to-diameter ratio of 0.4 (Fig 19) (Nienow and Elson, 1988).
from the authors laboratory for C/T = 1/4 are given in Table Recent work suggests that the shape is similar with the
4. However, the above comments on the effects of geometry pitched blade turbine (Elson, 1988), A315s (Galindo and
and possibly of scale should be borne in mind. Nienow, 1992) and Scuba 6SRGTs (Galindo and Nienow,
1993). For such broths, adequate liquid mixing and motion is
Shear stress - shear rate from impeller rheometers often the most energy demanding task that the agitators are
By measuring the torque from an impeller on a rheometer required to perform.
head for a Newtonian fluid, from Eqs (19), (23), and (24),
one gets Flow numbers
M = K/ND 3 The flow number, F1, is another useful dimensionless group,
I.t (30) defined as
2n
whilst from Eqs (2), (3) and (25) F1 = Q/ND 3 (33)
It. = x/;f = K~"-" = K ( k s N ) " - ' (31) There are far fewer F1 data in the literature, especially for Re
< 2 x 104. Care must be taken over defining Q which is the
so that on further re-arrangement with p= laa flow just off the blade, ie, for the Rushton turbine, the inte-
M = K / K k ~ -I N " D 3 (32) gral of the velocity over the blade height (= 0.2D) through
2~ the area swept out by the blade tip. The actual velocity pro-
To use this approach, Ki must first be determined from Eq file is of the form shown in Fig 20, ie, bell-shaped (Dyster et
(30) for the impeller to be used in the rheometer (7_ 80 for a al, 1993) giving values of F1 of about 0.78 (Harnby et al,
Rushton turbine) in a viscous Newtonian fluid (Re < 10). 1992) with a maximum velocity relative to the blade tip velo-
Secondly, values of K and n are obtained from a conventional city, nND, of about 0.8. The total entrained flow may be as
cone and plate or concentric cylinder rheometer for a range much as 2.5 times greater than this (Wu and Patterson, 1989).
of single phase non-Newtonian fluids and thus ks for the
rheometer impeller (7.. 13 for a Rushton turbine). From Eq
(32), therefore, i f M is measured as a function of N for a my- ~'-"~ ~k~ entrained
celial broth of unknown rheological properties, then K and n
can both be determined. For further details, see Bongenaar et
al (1973) and Baker (1988).

Flow patterns in non-Newtonian fluids

As the fluid becomes non-Newtonian shear thinning, changes
of flow pattern occur much as with viscous fluids as de-
scribed earlier, the most noticeable difference being the way
axial flows are even more prone to become radial and the ntraincd
tendency for the movement to be constrained to the impeller
region is reinforced. Both these effects are enhanced in poly-
saccharide broths since they are Fig 20. The discharge velocity off the tip of a Rushton turbine.
also viscoelastic. In addition,
both flow reversal and shaft
climbing may occur (Solomon et
al, 1981), though these latter ef-
C- FI = 0 . 7 8
fects are not generally found at
the industrial scale, (Nienow and d3
E
Elson, 1988). Z
In very viscous, highly shear- O
3= o" water
C O.1 100~ Glycerol
._Lc thinning fermentations (with n
Glycerol solution
values of the order of 0.2 or less) Glucose =altttion

whatever the reason for these P-E-G.

particular rheologieal properties, O.O1 =

I. pc -! agitation tends to cause cavern 1.O 10 10

Z
10
.~
10
J*
IO

Fig 19. Right circular cyl- formation, ie, regions of intense

Reynolds Number (Re)

inder cavern model. Fig 21. FI versus Re for a Rushton turbine.

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 14 SPECIAL
ISSUE:FLUIDMECHANICSPROBLEMSINBIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

Table 4. Some Power (Po) and Flow (F/) quency equal to the blade passage frequency. By shaft en-
Numbers (Re > 2 x 104) coding, it is possible to eliminate the contribution from the
blade passage frequency and this has been done by Wu and
Type Po FI Ref Patterson (1989) for example for Rushton turbines. They
6 blade Rushton turbine 5.2 0.72 A found that if they normalised their intensity in relation to the
5.0 0.74 B blade tip velocity nND, they obtained values o f ~ 0.3 with the
12 blade Rushton turbine 7.5 B periodicity included and of ~ 0.2 without it. Jaworski et al
18 blade Rushton turbine 8.7 B (1991) estimated an equivalent normalised intensity for a
Scaba 1.45 B pitched blade turbine in water with the periodic component
Chemineer HE3 0.3 0.41 B included and obtained very similar values to that of the
4 blade, 45 pitch turbine 1.27 0.79 A Rushton turbine. As the viscosity increases, r.m.s, velocity
6 blade, 45 pitch turbine 1.70 0.73 B fluctuations fall to a near constant value which is almost en-
6 blade Prochem Maxflo T 1.58 0.82 B
tirely the result of the blade passage at Re < ~ 100 (Dyster et
A315 0.75 0.73 A
al, 1993).
0.84 B
Intermig (one stage) 0.31 B
Energy spectra have been summarised by Tatterson
(1991) and these show a large peak at the blade passage fre-
A: Weetmanand Oldshue (1988)
B: FromMixingGroup,The Universityof Birmingham quency as would be expected. Local energy dissipation rates
have also been determined by many techniques since a rather
With a pitched blade turbine, it is the volumetric flow rate crude streak photography method was used by Cutter (1966).
through the swept circle directly below the lower edge of the Since eventually all of the power which goes from the shaft
impeller that is used, giving values of about 0.71 for a 45 to the agitator into the fluid is dissipated as heat, the mean
pitch, 6-blade impeller, again with a much higher entrained energy dissipation rate, Er, is defined as Er = P / P le Cut-
flow (Jaworski et al, 1991): Values for other impellers are
also given in Table 4. As can be seen, though F I varies with ter (1966) found that CT in the impeller swept volume was 70
impeller type, the variation in the turbulent region is much ET and that in the discharge stream 3.5 ET with 48% of the
less than that of Po. A recent paper (Herbert et al, 1994) has total being dissipated in those two regions respectively with
suggested that for pitched blade turbines and hydrofoils 30% in the remainder to give values of 0.26 ET there. Simi-
FI = 0.76Po u3 (34) lar results have been obtained by others, eg, Wu and Patter-
and unpublished data from our laboratory is in quite good son (1989) Geisler et al (1994) (Fig 22),Calabrese and Stoots
agreement giving a value of the constant of about 0.65. (1989) for the Rushton turbine using LDA. Though the ab-
With increasing viscosity, the F I starts to fall at Re 7_ 103 solute values of (ST)max /~T have varied from around 20 to
(Dyster et al, 1993). Data for Rushton turbines are presented about 100, they have all been much bigger in the impeller re-
in Fig 21 for Newtonian fluids and the fall is greater with gion than anywhere else in the vessel. This discrepancy is not
highly shear thinning ones (Koutsakos et al, 1990). Similar so surprising given the errors inherent in estimating local 8T
effects have been reported for A315 impellers (Weetman and values from the raw LDA data. The work of Jaworski et al
Coyle, 1989) and for Prochem Maxflo T's (Jaworski and
Nienow, 1994). All these recent results in fluids of higher
viscosity have been obtained with LDA as the measuring
technique since hot film ane-
mometry is then unsuitable.
Disc
Turbulence intensity
_L
N
0.5-
and local energy Brid-e - ~
dissipation rates
O3
Turbulence intensity is high-
- C est in the impeller discharge
stream, though the relative
(a)
0-
intensity may be greater else-
where because the mean
Dir~cLion/ ~
value is so low. However,
-0.25 j most measurements in the
o.~s o'.s 0.72 .o literature have concentrated
Vessel radius 2r/T on the discharge region. One
6-blade Disc turbine of the problems with obtain-
D/T = 0.33 ing the real turbulence inten-
Fig 22. Locarenergy dissipation sity (turbulence fluctuations)
(b)
rates with Rushton turbines arises because the flow is in-
Fig 23. Flow around a Rushton turbine blade showing a) trailing
(Geisler etal, 1994). herently periodic with a fro-
vortices and b) stagnation points

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 Appl Mech Rev vo151, n o 1, JanuarY 1998 Nienow: Hydrodynamics of stirred bioreactors 15

(1991) suggests that at equal D/T values, for different agita-
tors, the ratio (eT)m~x/E T is approximately the same though
Geissler et al (1994) proposed that it was proportional to
p o 1/3.
Similar very high local values are obtained if the simple
assumption is made that all the energy is dissipated in the
swept volume of the agitator (Davies, 1985). This approach
has been used quite successfully in treating droplet break-up
from different equipment.
some workers suggest that full axial flow is lost at such
spacing with A315s (Mannikowski et al, 1994) though others
(Bakker et al, 1994) have reported that axial flow is main-
tained at AC up to 3D for HE3 impellers. A closer spacing,
as with Rushtons, might well be advantageous with high vis-
cosity shear thinning broths. The unaerated power number of
two Intermigs of 0.7 (Table 4) is based on a D / T ratio of
0.6 to 0.7 and an impeller spacing AC = 0.5. This spacing is
used for both low viscosity and high viscosity broths.

Flow close to and behind impeller blades

Behind an impeller blade, intense high speed rotating vor-
tices form, 2 per blade for Rushton turbines with maximum
shear rates up to - 100N (Van't Riet and Smith, 1975) (Fig
23a) and one per blade for pitched blade turbines (Tatterson
et al, 1980) and hydrofoil impellers (Martin et al, 1993).
van't Riet and Smith (1975) studied them using a camera ro-
tating with the impeller whilst Nienow and Wisdom (1974)
used strobe lighting. The most flexible approach is probably
the de-rotational prism (Kuboi et al, 1983). Only the flow on
the Rushton turbine blades has been well characterised and
Fig 23b shows the front and back stagnation points.
Multiple impellers
The power drawn by dual or more gushton turbines depends
on the impeller spacing, AC. Fig 24a shows how the flow
patterns change with spacing in low viscosity broths and Fig
24b shows the change in power draw (Hudcova et al, 1989).
A spacing of one vessel diameter is recommended for such
broths, when the power number for n impellers, (Po) n, is
given by (Po)n = n Po.
In high viscosity shear thinning broths, cavern formation
tends to occur which calls for a closer impeller spacing
(Nienow and EIson, 1988). The height-to-diameter ratio of
caverns with Rushtons is 0.4 and an optimum spacing is one
such that the caverns meet at the same speed as they reach
the wall.
Prochem and A315 agitators are normally used with an
impeller spacing of about one vessel diameter or a little less
and then the simple summation of Po applies. However,
MIXING/HOMOGENIZATION
OF THE BROTH WITHOUT AERATION
Mixing of the fermentation broth to homogenise it is a crucial
feature which affects bioprocesses. Essentially, in shake
flasks, a broth of homogeneous composition can reasonably
be assumed. In large bioreactors, this homogeneity is clearly
not present as discussed earlier. Until recently, this question
has mainly be quantified by a parameter called the mixing
time which is the time taken to homogenise the liquid con-
tents of the bioreactor after a step change in composition.
Experimental methods for doing this are numerous and typi-
cal properties utilised to follow the progress of homogeniza-
tion are conductivity (Otomo et al, 1993) and pH (Singh et
al, 1986). Special precautions must be taken if the system is
aerated when conductivity is employed since the bubbles in-
terfere with the probes response (Otomo et al, 1993).
Fluorometric probes have also proved useful in real fer-
menters (Groen et al, 1993).
Another very useful technique in the laboratory is based
on decoiorization of a starch/iodine solution by sodium thio-
sulphate (Cronin et al, 1994). This technique is particularly
valuable with multiple impellers as it allows the progress of
homogenization from impeller to impeller to be followed. It
also is good at revealing the presence of stagnant zones in
high aspect ratio systems and in shear thinning fluids, espe-
cially those with a yield stress (Nienow and Elson, 1988).
T u r b u l e n t flow with a single impeller
Theory
There are two main approaches. One is based on bulk flow
concepts, particular based on flow numbers (Nienow,
AC/T
% 2/3 1
I I I

0
2.0 0 ,,,.~....~.. 0 ~ cJ

1.8 .~ .
g

O T O/T HIT
/ 0 0"56 0.33 2 8, I
1"2 --/
I 0 0"29 0"33 2
I 0"45 0"33 1
1'0 ~'~'0 n e impeller ~ 0.64 0"/,0 2

I I I I I I I = ?
0 0"2 06 1"0 1.//. 1.8 2'2 2"6 3"0
,~ ~J! zxc/o(o=~hT}
(a) (b)
Fig 24. The effect of impeller spacing with Rushton turbines on a) flow patterns; and b) power draw.

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 16 SPECIALISSUE: FLUID MECHANICS PROBLEMS IN BIOTECHNOLOGY Appl Mech Rov vol 51, no 1, January 1998

1990a); or on impeller discharge velocity (van't Riet and Table 5. Predictions of Impact of Certain Parameters on 0m
Tramper, 1991). The other makes use of integral scales of Based on the Turbulence Model and the Circulation Model
turbulence and their relationship to turbulent diffusion and Scale at D at Agitator D/Tat Const.
the decay of concentration gradients (Corrsin, 1964). Each of Model eonst. Speed equal Type Const. P-M-N
these will now be briefly described. P/pV P at equal Speed Retro-
The flow approach (Nienow, 1990a) is particularly justi- P and D/T fitting
fied by imagining an idealised probe response following the
addition of a tracer as shown in Fig 25, though experimen- Circulation (Scale)2/3 Nt D"4/3 pol/3/FI (D/T)"3 Po0"6
tally, such an idealised response is rarely found. It is then ar-
gued that the time between peaks, the circulation time 0c, is Turbulence (Scale)2/3 N "1 D"1/3 All equal (D/T) "2 Po1/15
given by OmULD-413 (40)
0c : V/Q = V/FIND 3 (35) On the other hand, scale-up with geometric similarity, ie, Vt
for a vessel of aspect ratio of about 1. It is then suggested D 3, gives from Eq (36)
that the system is homogenised after about 5 circulations
Omcd/N (41)
(Khang and Levenspiel, 1976) so that
or, if equal power per unit mass is used on the different
0m = 5V/FIND 3 (36)
scales with D et T so that
and for H = T so that V = ~xT3/4 PoN3D 5
E r = P / prct ~ otN3T 2 = constant, (42)
OmN = 3.9(D/T) -3 FI -t (37)
Equation (35) can be re-arranged in a variety of ways. For then
example, Omt~T2/3 (43)
Omt~V/ FI( N3 DS) I/3 D 4/3 (38) These functional relationships are given in Table 5.
and since P ot PoN3D 5, The turbulence model has recently been outlined by
Ruszkowski (1994) and here it is developed in more detail. It
Om~V / Fl( e / eo) l/3 D 4/3 follows earlier theoretical contributions from Corrsin (1964),
Therefore, in a particular vessel size if different types of im- Brodkey (1975) and Evangelista et al (1969). In its simplest
peller of equal diameter are compared at equal power form, the theory suggests that the mixing time is inversely
Omct(eo)l/3 /Fl (39) proportional to turbulent diffusion so that
t . 2\-1/3
or if the same type of impeller but of different size are com- OmaleT/Lc) (44)
pared,
where 8T is the local energy dissipation rate and Lc is the in-
tracer tegral scale of turbulence.
This equation does not distinguish between impellers and
requires two problems to be addressed before it can be di-
rectly used. Firstly, what eT value should be chosen? It is
well known that the ratio of the maximum energy dissipation
rate, (8T)max, which is close to the impeller, compared to the
average is quite large, of the order of 20 to 100 (Cutter,
1966; Calabrese and Stoots, 1989). Also, it is reasonable to
assume that the slowest mixing due to turbulence will be
detector --.....n,/,- where eT is at its lowest value, ie, close to the wall, (ET)T.
However, there is little evidence that, for impellers of the
same D/T ratio, (eT)T/~T is markedly different for different
tracer I'~"0C""~ I
concenlradon impellers (see, for example, Jaworski et al, 1991). Assuming
these ratios are the same for all impellers, then one might ex-
pect to find that
Coo '----I.... ..... 0 m = Ai(eT) -'/3 (45)
where A i would be independent of impeller type for a par-
ticular D / T ratio. Such a result has been reported by
0 Ruszkowski (1994) and by Cooke et a! (1988), both of whom
have used a large range of impellers and scales of operation
add time mixing
at energy dissipation rates of the order of I W/kg.
tracer tiloe, Om
If it is taken therefore that
Mixing time measurement
Oma(ST) -I/3 (46)
Fig 25. Ideal conductivity probe response after injection of a s o -
dium chloride solution as tracer.

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 Appl Mech Rev vol 51, no 1, January 1998 Nienow: Hydrodynamics of stirred bioreactors 17

then
Q et ND ~ (55)
Omcd/N (47)
then for an impeller in a vessel of diameter T at constant ~ r ,
and
Q is related to the impeller size by the relationship
0raN= constant, (48)
O ~ (D/T) 4/3 (56)
which is the same result as with the other model (Eq (41)).
Comparison of Eq (54) with Eq (56) would suggest that as
Cooke et al (1988) and Ruszkowski (1994) reported that the flow throughout the bulk of the vessel is enhanced by in-
increasing D/T ratio also reduced mixing time at equal speeds creasing D/Tratio (Eq (56)), so the energy dissipation rate in
with a functionality
that bulk region, (eT)T, relative to that in the impeller region
Omot(D/T) -2 (49) increases approximately proportionally (Eq (54)).
This would appear quite the opposite to Eq (44) ifLc ~ D, ie, The overall equations given by Ruszkowski (1994) and
if the integral scale of turbulence is proportional to the im- Cooke et al (1988), each based on a large amount of work on
peller diameter. However, whilst this proportionality for the scales up to 3m diameter, for H = T can be written as
integral scale has been shown to apply for the flow close to A ( " "~(
~ 11 D T -2
the agitator (Brodkey (1975), Cutter (1966)), if it is the flow
well away from the agitator that determines the mixing time, where Ruszkowski gives A2 = 5.3. Rearranging Eq (57) gives
it is the tank diameter to which the integral scale should be f o r H = T,
related, ie, Lc ct T so that from Eq (44). 0 m 5.9T213(ET)-I/3(D/T) -I/3
= (58)
Omo~T2/3 (50)
The implications for improved mixing by increasing D/T are
at constant eT, again in agreement with the other model (Eq similar to those for the circulation time theory but much less
(43)). This discussion therefore supports the conclusion that effective (see Table 5 for a full comparison).
the correct integral scale is one proportional to the vessel di-
ameter, T. Experimental results
The experimental observation that Omot(D/T)"2 suggests Ruszkowski (1994) used a range of impellers at energy dissi-
that large D/T ratios give a more even distribution of energypation rates of the order of 1W/kg with D/T ratios from 1/4 to
throughout the vessel and, in particular, enhance it in the 1/2 in vessels with H = Tup to 2.7m diameter. He also used a
complex multiple conductivity probe technique to obtain 0m.
bulk, ie, (eT)T (Geissler et al, 1994). Therefore, from Eq (44)
Cooke et al (1988) studied a similar wide range of scales and
with Lc tz Tand er = (er)7, impellers. Hass and Nienow (1989) used the decolorization
Om(~,(~TIT2)-I/3(ET)r-"3 (51) technique to determine mixing times in a comparison of the
performance of a Prochem Maxflo T axial flow hydrofoil
where (~T) =(eT)T/(~T). If it is assumed that with a Rushton turbine of the same diameter. Their results
are given in Fig 26 and compared with Eq (58) which can be
(eT)r,(D/ T)" then, seen to be in very good agreement. Fig 27 compares a radial
flow Scaba 6SRGT with an equal-sized Rushton turbine
Oma(gT/T2)-I/3(D/T) -el3 (52)
(Saito et al, 1992) and again good agreement with Eq (58) is
so that from Eqs (20) and (42), one gets seen. These independent results from impellers with very dif-
p -1/3 ferent Po numbers and flow patterns strongly suggest that the
O -53 -a/3
Omct---~--(D/T ) (D/T) ( 5 3 ) turbulence theory which does not distinguish between im-
pellers is preferable for single impellers. A recent test of 8
which suggests by comparison with Eq (49) that ct = l,
(54) /
L D = TI3
20
Since from Eq (33), slope- %
,oL. I- C = TI 4

Rushton Prochem
turbine impeller
~- -l-nrn- . - I/3 ~. 0 VVm
~ Q ~,,.~,,._
--~.. ~/ o 0.Svvm
I0 0 ~ , . . ~^ . . , ~~ o I ' 0 vvm 5 Air - w a t e r
n ' " " ~ ' ~ o.~ Ills ,i, O 1.5 vvm
<oe From Equ. 55
,g Qg Rushton
[vvm] 6SRGT turbine T = 0.61m
r = O'S6m o~ ~-:~..~. 0 o
D :* TIz E
2 0.5 ~
From Equ.S8 1'0 .o
l = I i I J I,tl I i i I ,=,~i
I I I I I I I I
20 S0 100 200 500 1000 2000 5000 10 -I I 5 I0

lET) or (ET)g (Wlkg x 10 :l) (E T) or (ETI 9 ( W l k 9)

Fig 26. Mixing times as a function of mean energy dissipation rate Fig 27. Mixing times as a function of mean energy dissipation rate
for equal sized Prochem and Rushton turbines. for equal sized Scaba 6SRGT and Rushton turbines.

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 18 SPECIALISSUE:FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY
impellers at very low specific energy dissipation rates of 8
W/m 3 by Shaw (1994) also gave equal 0m values for all im-
pellers of equal D/T ratio.
Equation 57 giving Omo~(D/T)"2 at constant N is also in
close agreement with many empirical correlations as summa-
rised by Tatterson (1991) whilst Eq (36) implies Omot(D/T) "3
since Yt 73 (Table 5). Whilst this latter relationship is in ac-
cord with the recent model of Van't Riet and Tramper (1991)
and the model and experimental results of Groen et al
(1993), on balance, the literature supports the integral scale
model for single impellers in vessels of H/T= 1.
Transitional flow
If viscosity is increased, then at Re 7_ 6400 Po -1/3 (Grenville
et al, 1995) ie, close to the value at which FI starts to fall, the
mixing time begins to increase in proportion to la so that
0raN = 3.4xl 04 Re-Ipo-2/3(D/T) -2 (59)
particularly due to the time taken for homogenization in the
wall region. The trend to longer 0m is even greater for shear
thinning fluids though a good way of allowing for the effect
of spatial viscosity variation on 0m has not been proposed as
yet in the open literature.
Yield stress fluids
In these fluids, away from the impeller, where shear stresses
are low, the fluid may be stagnant if the fluid yield stress is
not exceeded. Thus, around the impeller a cavern of mixed
fluid may form surrounded by stagnant fluid. Flow visualiza-
tion by a laser light sheet and video recording gives good
support for this physical representation (Jaworski et al,
1994). The boundary of the cavern can be defined as the sur-
face where the local shear stress equals the fluid yield stress.
If it is assumed that the predominant flow in the cavern is
tangential (and LDA studies suggest that this is a reasonable
approximation (Hirata et al, 1994)), and that the cavern
shape, fluid yield stress and impeller power consumption are
known, then the cavern size may be determined. A right cir-
cular cylinder of height Hc and diameter Dc centered on the
impeller, (Fig 19) is a good model which allows for the effect
of different impellers (Elson et al, 1986). Thus,
(-~-) =[ ", .(Hc/D;+~/3)n2 (60)
A typical Hc/Dc value for a Rushton turbine and a Scaba
6SRGT is 0.4 but for an axial flow propeller and an A315 it
is nearer 0.75 and 0.6 respectively. Once the cavern reaches
the wall, it increases proportionally with N for a Rushton
(Nienow and Elson~ 1988) and a pitched blade turbine
(Elson, 1988) but proportional to N0"5 for the Scaba (Galindo
and Nienow, 1993) and A315 (Galindo and Nienow, 1992).
For Rushton turbines for Re > -30, Po Z constant. There-
fore, at a given scale, larger caverns can be achieved for a
given power input by using a large, slow agitator, as for this
5/9
case Dc otD (Nienow and Elson, 1988). Offset against this
is the increase in torque on the impeller shaft:, M, where for
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Appl Mech Rev vol 51, no 1, January 1998
this case M ~ D 5/3. Scale-up under geometric similarity and
constant power per unit mass (or mean energy dissipation
rate) again for Po = constant gives Dc/T o~ D 2/9, ie, the di-
ameter of the cavern relative to the tank diameter, T, or the
proportion of fluid in the tank mixed, increases with scale at
constant power per unit mass. For impellers for which Po in-
creases as Re decreases, the effect of D/T and scale is less
pronounced.
Multiple impeller systems
Mixing time as a single parameter has been reported for mul-
tiple impeller systems by Cooke et al (1988). They found the
time increased very significantly but did not distinguish
whether the increase was due particularly to the increase in
height or the extra number of impellers. The equation that
they gave is similar to Eq (57) viz
0= = . tNJt~oJ t,HJ (61)
for multiple Rushton turbines.
Cronin et al (1994) showed by a decolodzation technique
the staged mixing associated with radial flow turbines and
Otomo et al (1995) showed similar results with hollow blade
radial flow turbines. However, by using conductivity probes
in each of the four zones associated with two Rushton tur-
bines (Fig 24a), the latter workers found that 0 m for each
probe at the 95% level (Fig 25) was almost the same when
injecting salt solution into the upper flow loop of the top im-
peller. This time was about twice as long as with a single im-
peller, thus confirming the results of Cooke et al (1988). On
the other hand, the actual probe response to the pulse injec-
tion was quite different with the upper probes giving a large
overshoot and the lowest ones a gradual approach to equilib-
rium (Fig 28). These responses could be modeled well by es-
timating exchange flow rates, QE, which when expressed as
exchange flow numbers, FIE, (= QE/ND 3) had values of about
1.4 for exchange from zone 1 to 2 and 3 to 4 and about 0.4
for exchange from 2 to 3, ie, from the upper to the lower im-
peller. These values should be compared to the Rushton tur-
bines flow number of about 0.8.
When using two A315, Otomo et al (1995) found that the
compartments were not well described as above, though
some zoning does occur as was also indicated by the work of
Manikowski et al (1994) using an ultrasonic Doppler probe
to characterise the flow. The latter used two A315s above a
Rushton and both studies also confirmed the results of Cooke
et a! (1988) that the axial flow hydrofoils significantly reduce
the mixing time compared to radial flow impellers, typically
by a factor of about 2 at the same energy input.
Some studies have used a model with one cell per agitator,
regardless of the type and comPared it to data obtained by in-
jecting at the top and with a single conductivity probe at the
base. Thus, Jahoda and Machon (1994) studied Rushton tur-
bines and pitched blade turbines pumping either down or up.
They found FIE 7_0.32 for both types in agreement with other
earlier work. Thus, this result is in good agreement with that
of Otomo et al (1995) and it implies that equal mixing times
occur at equal agitator speed and diameter and therefore con-
 Appl Mech Rev vol 51, no 1, January 1998 Nienow: Hydrodynamics of stirred bioreactors 19

firm that axial flow impellers give shorter mixing times at
equal energy inputs because of their lower power nos.
A slightly different approach uses a plug flow with diffu-
sion model (Groen et al, 1993). In this case, the length of the
diffusion path is H + n T for n equally spaced Rushton tur-
bines and the diffusion coefficient is estimated from an ap-
plication of Kolmogoroffs theory for the inertial sub-range.
Though data fitted the theory quite well up to 150m3, the re-
lationship includes viscosity which it should not if Kol-
mogoroff's theory is applied correctly; and the functionality
for a single stage gives a relationship for the effect of D/T
equivalent to that from the circulation model as discussed
earlier. Unfortunately, the effect of D/T was never tested. Ja-
hoda et al (1994), on the other hand, used a similar approach
and obtained equations for mixing time essentially equivalent
to Cooke et al (1988).
Another way of obtaining the flow structure is by the use
of flow followers and using them to measure exchange flow
rates (Mann and Rubinovitch, 1983). This technique also
shows the considerably reduced exchange flow rate in more
viscous systems (Kuboi et al, 1986). Recently, Vasconcelos
et al (1995) have used this technique together with a three
compartment/agitator model to analyze mixing time data with
three Rushton turbines.
All other models have been for Rushton turbines and have
been of considerably greater complexity. Mostly, they use
two zones per agitator but add additional well-mixed com-
partments in the circulation loops (Singh et al, 1986; 1988;
Mayr et al, 1994) so that 4 or more parameters are fitted. It
would appear that this approach is rapidly reaching the situa-
tion where the artificial complexity of the model outweighs
its usefulness. Perhaps recent developments in computational
fluid dynamics will become a more fruitful approach.
Thus, though for single impellers, Eq (57) suggests that
the mixing time in a single impeller system is independent of
impeller type, it makes a very big difference in multiple im-
peller systems. Indeed, further improvement in bulk blending
Lower impeller region Upper impellerregion
Probe i Probe 3
0.5 ~ a)
are certainly possible, eg, see John et al (1995) who used a
model of the RHM configuration shown in Fig 3. Enhanced
blending can be expected to give an improved fermentation
performance on the large scale as the conditions then more
closely mimic those of the small.
AERATION CONSIDERATIONS
The oxygen uptake rate varies enormously from one biologi-
cal species to another; for example, animal cells requires
about two orders of magnitude less than a vigorous bacterial
fermentation (Nienow, 1991). However, if the bioproduction
is sufficiently successful on scale-up that the concentration of
the active biomass reaches the same as that in the laboratory,
the oxygen requirements will be proportional to the volume
in each case. This type of reasoning has led to constant spe-
cific volumetric flow rates being used at different scales, ie,
the volumetric flow rate of air per minute per volume of
broth, QGV. A typical value from experience for bacterial or
mycelial fermentations is of the order of to 1 vvm though
in animal cell culture as little as 0.01 vvm may be sufficient
(Oh et al, 1989).
Therefore if the volumetric air flow rate is QG(m3/s)
QGV = 4(60Q6)/rcT2 H (62)
Superficial air velocity, Vs, is often used in correlating mass
transfer results and this typically increases with scale since
v s = 4QG/r~T2otHQGv (63)
These air flow rates are also often expressed in dimensionless
form as gas flow or aeration numbers FIG where
FIG = QG / ND3 (64)
BASIC PARAMETERS OF AGITATION
WITH AERATED RUSHTON TURBINES
Bulk flow patterns
Low viscosity broths
If the air flowrate is too high for the agitation conditions, the
air flow dominates the bulk flow pattern and the air is poorly
dispersed. This condition is known as flooding and is to be
avoided, Fig 29a. For Rushton turbines in broths with vis-

Increasing QG
[ P Constant N
0 20 =0 60 0 20 40 60 (a) (b) (c)
Time [st Time [sl
C)N NF C" c__~..
N
I-IN
Probe 2 Probe 4
0.5 0.5
gild2
~ T , a -~'H '/.
": II ~ " ' I " I . L
q
o
H=T Constant aG
0[ I Increasing N
20 aO 60 2o 40 60
Time IS] r~me [sl Fig 29. 'The tlooding-loading-compiete dispersion transitions for a
Fig 28. The response of conductivity probes in the zones 1, 2, 3, Rushton turbine a) flooded; b) loaded; c) completely dispersed
and 4 (see Fig 24a). (Nienow et al, 1985b).

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 20 SPECIALISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

' cosities not much greater than water, the correlation (Nienow
et al, 1985b)
( F/c )r = 30( D/ T)35( Fr) F
enables the minimum agitator speed required to prevent
flooding, NF; to be calculated. In this equation, Fr is the
Froude number, N2D/g, proportional to the ratio of the iner-
tial to buoyancy forces; and FIG is the gas flow number, pro-
portional to the ratio o f the air flow rate from the sparger to
the pumping capacity of the agitator.
Equation 65 has implications for the choice of D/T ratio,
since for constant aeration rate and vessel size (Nienow,
1990b),
1/ NFD3 ~xD3"SNF2 D (66)
so that
N FaD -2"5
For constant pumping rate, Nct D -3. Thus, this relationship
might be taken to imply that, at a fixed scale of operation,
constant pumping rate is required to disperse a given flow
rate of air, D 2~ rather than O -3 arising because the flow num-
ber is a weak function of D/T. From Eqs (21) and (67),
PF a N3DSaD -2"5
ie, less power is required to disperse a given aeration rate
with large D/T ratios at a particular scale of operation.
Rearranging Eq (65) gives
NFa[(T/D)3"5(1/D' )]'/3QGI/3
SOthat at constant T and D
(ONF/OQc)Do.D-2SQc-2/3 / 3
Thus, the flooding-loading transition of Fig 29 (a-b) is more
sensitive to aeration at small D/T. For T/3 Rushton turbines,
the transition can be delayed, ie, about 50% more air can be
handled before flooding occurs, by using a sparger about
1.2D (Nienow et al, 1988).
To completely disperse the air into the lower part of the
vessel (Fig 29b-c), a higher speed, Nco, is required which for
Rushton turbines (Nienow et al, 1985) is given by
( Fl6 )co = 0.2(o/r)5(Fr)co 5
Assessing the choice of D/T as above gives NCD(xD-2 and
P CDaD" Ii
As the agitator speed increases above NF, the extent of air
recirculation steadily increases and can become very high at
speeds approximating to NR and above (Nienow et al, 1978)
(,) , ' (b) (e~
Vortex * Clin Ing 3-3"
cavities cavig[e
t s structure
leading to a well-mixed gas phase. For single disc turbines,
NR, can be calculated from
(65) ( FIc)R = 13(Fr)R2(D/T) 5 (72)
The amount of recirculation has been quantified by gas tracer
techniques (Nienow et al, 1979) for a single disc turbine and
the volumetric flow rate of gas recirculating can be 3 or more
times the air sparged. This is particularly so on the small
scale and laboratory fermenters usually have a very well
mixed gas phase.
Surface aeration, ie, ingestion of air bubbles, through the
top surface occurs at high agitator speed under unaerated
conditions and has often been stated to be significant, espe-
cially on the small scale as a means of providing oxygen
transfer. However, experiments have shown this not to be so
at typical aeration rates for fermentations on all scales
(67) (Chapman et al, 1980).
Effect of increasing viscosity
For Newtonian broths with viscosities in the range 1 to 100
mPas, an increase in speed is required such that both NF and
Nc a(~t a)o.I (Nienow and Ulbrecht, 1985; Bujalski, 1986).
(68)
For shear thinning broths, it is difficult to define a precise
flooding point or determine a value for N F. A minimum
speed is required to cause break-up of air (Solomon et al,
1981). However, even at speeds above that which cause very
fine bubbles to be produced and mixed throughout those re-
(69) gions of the vessel which are in motion, very large bubbles
are also still to be found bursting through the top surface of
the broth. A very wide, mainly bimodal, distribution of bub-
(70)
ble sizes is obtained with many very small (< 0.5 ram) bub-
bles following the fluid and a relatively few in number (but a
high proportion in volume) of very large bubbles in plug
flow. The small bubbles recirculate many times (Nienow,
1984).
With a very high viscosity, shear thinning broth with a
yield stress, cavern formation again occurs. Equation (60)
can again be used provided the aerated power number (Pog)
replaces Po.
(71) Hydrodynamics local to the agitator
Low viscosity systems
If a Rushton turbine is imparting a power input of about
l W/kg to a low viscosity broth, then on introducing a stead-
ily increasing rate of air input, ventilated cavities of increas-
ing size develop behind the impeller blades. These are re-
gions of low pressure where vortices exist under unaerated
(a) conditions. This is a complex process which has been very
carefully analyzed for Rushton disc turbines (Nienow et al,
1985; Warmoeskerken and Smith, 1985). At a fixed speed,
regardless of agitator type, above a certain air flow rate,
flooding occurs. With a power input greater or less than 1
W/kg, greater or lower air flow rates respectively can be
oo~F,e,
Ra ed

Constant N
handled before flooding. However, essentially the same se-
Increasing Q quence of cavity structures is passed through between zero
Fig 30. Change in cavity structure with increasing aeration rate for gas rate and flooding (Fig 30). On reducing, the gas flow rate
a Rushton turbine in low viscosity broths (Nienow et al, 1985b).

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 Appl Mech Rev vol 51, no 1, January 1998 Nienow: Hydrodynamics of stirred bioreactors 21

1'0 1-0 ' I 'I I ' I ' I ' l ' I '

1
~'\~ " I , DIT=0"6.
0"8 0"8
Pg/p Pg/p
Nls.t)
0"6 0-6 2

0'~ O.t~

I I I I I t , I ,l I , I , , . I i
0"02 0-06 0"06 0"08 0-10 0-12 0 0.02 0.06 0.06 0.08 0.10 0.12
FIo FIG
(a) (b)
Fig 31. A comparison for Rushton turbines of Pg/P versus FIG a) measured; b) calculated.
back to zero, the cavities also reduce in size to zero with little scales on log-log paper with 4 orders of magnitude on the y
hysteresis as compared to the increasing gas flow sequence.
axis and 8 onthex, one has a graph of Pg(~" N3DS) versus
High viscosity shear thinning broths
In such broths, even a small air input rate leads to the forma- N7 DI3/D "5) ie NT D 11"5.This analysis would suggest that
tion of large, stable, equal-sized cavities behind each agitator lines of slope around 3/7 (= 0.43) or 5/11.5 (= 0.43) would
blade. Increases in aeration rate do not change the cavity size result and that is exactly what has been found, not only for
significantly but increase both the rate and, to a lesser extent, single Rushton turbines but also for triple Rushtons and even
the size at which bubbles break away from them. As ex- for up to 7 pitched blade turbines whether pumping up or
plained earlier, flooding is not so readily defined but at high down (Seichter et al, 1992). This approach could correlate
aeration rates, the increased breakaway frequency and bubble any randomly selected values of N and D for every single
size at breakaway leads to enhanced coalescence of bubbles, impeller or any combination of impellers!
so that bigger and bigger ones break through the top surface. The approach of Van't Riet (1975) is simple and is physi-
On decreasing aeration rate, cavities commonly remain be- cally based but the interpretation of cavity formation is now
hind the blades even down to zero air flow rate. This phe- known to be incorrect. A more direct approach by Smith et al
nomenon is accentuated if the broth is also significantly vis- (1987) combines cavity formation and gas recirculation con-
coelastic (Nienow et al, 1983; Ozcan-Taskin et al, 1992). cepts with empiricism. For vortex and clinging cavities, 0 <
Power drawn FIG < (FlG)3-3 where
Low viscosity broths (FIG)3_3=3.8xlO-3(Re2/Fr)'7(T/D) 0"5 (73)
"In general, in low viscosity systems, the power drawn at con- then
stant impeller speed falls as the aeration rate increases due to
Pg/P= 1-16.7(FIG)(Fr) '35 (74)
the growing cavity size. However, the aerated power number
will also fall a little even under constant aerated conditions For small 3-3 cavities, (FIG)3-3 < FIG < O.1,
with increasing agitator speed due to increased amounts of
gas recirculation. These phenomena are well-known for stan- A-B + (A-B~Flc) (75)
dard Rushton turbines. Values of half or a little less of the
unaerated power are not uncommon and many attempts have where
been made to correlate the power data. Fr ) 0.35
A
=
1-17(F1c)3_3( (76)
The method most often claimed to be successful is the
entirely empirical approach of Michel and Miller (1962). and
However, its success is a n artifact of the data treatment. B = 0.27 + 0.022(Fr)-' (77)
The aerated Pg is plotted against a dimensional group,
For large 3-3 cavities and 0. ! < ( Fl6 ) < ( FIc )F
(p2ND3/QG'56)on double logarithmic paper. However, 1 >
Pg/P = 0.27 + 0.OZ2(Fr)-' (78)
Pg/P >. ~ 0.4, Pg a N3 D 5 , PouV3D5 and typically, on differ-
This very extensive set of relationships is a measure of the
ent scales, aeration at constant vvm is used as discussed ear- complexity of the problem and Fig 31 compares them with
experimental data. However, the equations have not been
lier. Therefore, Qc ~t D 3 so that QG
0"56~ D t'5 . Combining all
tested against large scale data in the open literature.
these relationships and then plotting the data from different

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 22 SPECIALISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY Appl Meeh Rev vol 51, no 1, January 1998

Nevertheless, they offer a good approach and these Equa- above this minimum should be used for good air dispersion
tions for cavity structure can also be combined with those for (Nienow and Ulbrecht, 1985) but equations are not available
flow regimes to give flow maps (Smith el al, 1987), exam- for predicting this minimum point.
ples of which are shown in Fig 32.
Mixing time
High viscosity broths
Much less work has been conducted on mixing time in aer-
In these broths, increasing viscosity (often with increasing ated systems and there is considerable confusion in the early
viscoelasticity and the development of a yield stress) leads to literature. However, the reason for this appears to be that at
increasing stability of the large cavity structure referred to agitator speeds below NF, aeration improves mixing (Cronin
above. Cavity sizes (Fig 33) are independent of aeration rate et al, 1994) due to the action of the plume of air bubbles.
and as a result, so is the power drawn (Nienow, 1984). The Given that flooding is usually an undesirable condition, this
aerated power relative to the unaerated power passes through improvement is not particularly useful. At higher speeds, the
a minimum with increasing agitator speed (Fig 34) (Nienow mixing time seems to be somewhat increased under aerated
et al, 1983)leading to lower values than in low viscosity conditions for a fixed speed. However, given that aeration
systems. These effects have been ascribed to increasing vis- generally lowers the power input, such a finding follows the
coelasticity (Nienow et al, 1983; Ozcan-Taskin et al, 1992) trend implied by the correlations of Ruszkowski (1994) (Eq
and yield stress (Galindo and Nienow, 1992) and viscosity (57)) and Cooke et al (1988) (Eq (61)). Indeed, Cooke et al
alone (Ozcan et al, 1990) has also been invoked. Certainly, it (1988) found that all their data could be correlated whether
is true in high viscosity filamentous broths. Speeds at or aerated or unaerated by the same equation. Cronin et al
(1994), Haas and Nienow (1989) and Saito et al (1992) all
I i , i ,
- Fiow re;ime : , found that their mixing times with the same D/T ratio Rush-
ton turbine, Prochem Maxflo T and Scaba 6SRGT respec-
_~_*:_!:!"J_..... , ....... i___ ~ _ I tively were equal at the same values of (~T) and (Er)g.
- ; ~i-29c "~- ', 1
Cr = l w / w g
..............
', ~ / NCD
..___~__.q ........... ~--
" /
L
Blode
.
":'
..... ~'~.tLM'__
, ...S-.........
........ - .- . . .
~ ......
;
!.,

I I e

I I , i _

-, ~ . . . . ~~:
)i
~u

1
~

QG z 10 3
2
:i:,
~i

m3/s
i
- - - ?E,- -

3
>;
lbo

% Disc avity
(a) Rotationat o n eQch o f t h e
direction six blcldes
I i ;
Flow regime , Fig 33. A typical gas-filled cavity on a Rushton turbine (Re < 1000)
'~-r = z w/w~ ' , / N m (Nienow et al, 1983).

F'a 29C: ~ i
6b~ r=0.29m : 1/3T Rushton
2
me"r = o s w/ ;:_.,_Z__illi!222
' '', - q-W t
Z

1"0 O~o~ ==~......

'/ { ', "

i_i - ?E ~. o-s a
0.4.- /

i '. i i
0"2- a
10 ZO 30 LO o

O.G x 103 m3/s o-1 I I I I

so !00 500 lo00 s00o
(b) Re
Fig 32. Flow maps for a Rushton turbine in a) a 0.44 diameter ves- Fig 34. Pog versus Re for high viscosity fluids with Rushton tur-
sel; and b) a 1.2m diameter vessel (Nienow et al, 1985b). bines.

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 Appl Mech Rov vo151, no 1, January 1998 Nienow: Hydrodynamics of stirred bioroactors 23

Thus, it is suggested that Eqs (57) and (61) be used for aer- The power drawn by the lower impeller can be enhanced
ated conditions too, provided N > NF. up to about that of the upper impellers by using a large ring
sparger (Ds Z 1.2D) (Nienow et al, 1988).
Scale-up
Since N normally decreases with increasing seal and Qa ct Effect of depth and back pressure
D 3, if vvm (see Eq (62)) is held constant, it is clear that FIG The correlations for the flooding-loading transition and for
typically increases on scale,up. For example, at constant the relationship of Pg/P versus FIG have been shown to be
(er)g, scale-up with constant vvm gives dependent only on volumetric flow rate and not gas density,
ie, pressure (Takahashi and Nienow, 1992). Thus lower im-
N ~tD -2/3 (79) pellers (except the lowest) will draw a little more power than
upper ones since the volumetric flow rate is reduced with in-
so that creasing depth. Increasing back pressure also increases
power draw in proportion to the reduction in volumetric flow
FIG ct D 2/3 (80)
rate (Nienow et al, 1994).
In addition, large fermenters usually have an aspect ratio High viscosity broths
(H/T) greater than 1 to ensure a higher proportion of oxygen
in the sparged air is utilized as air compression is expensive. In high viscosity broths, the most demanding task for agita-
tors is the achievement of good blending and closer impeller
For an aspect ratio of etA. then spacings are called for as a result (Nienow et al, 1994). Since
FI6aaAD 2/3 (81) the cavity sizes are largely independent of aeration rate, each
agitator behaves as though it were on its own, ie, single agi-
Single turbines tator power characteristics are additive to give combined aer-
Larger flow numbers on scale-up inevitably lead to lower ated power characteristics.
Pg/P values as can be seen from Eqs (74) to (78) and in Fig
32. In addition, from Eq (65) at constant vvm and with geo- AERATED MIXING WITH OTHER AGITATORS
metric similarity
ct A/ N FCxNF2D (82) Possible improvements on Rushton turbines
so that on scale-up Power draw
I-/o. "d/373 The fall in the power draw of the Rushton turbine on aeration
j o=oo= ,=, causes a number of considerations. Either the motor must be
sized to cope with the unaerated full speed situation; or a two
ie, a higher specific energy dissipation rate or power/unit speed or variable speed motor must be provided; and even if
volume is required to prevent flooding on the large scale. it is, very exact safety cut outs must be introduced in order to
Alternatively, at the same power/unit volume, a single im- prevent motor burn out on air failure.
peller (or the lower one in a set) will be closer to flooding. Secondly, the power draw still cannot be predicted with
By the same reasoning (Nienow et al, 1985), complete air great precision even aRer many years of work. It should be
dispersion and gross recirculation also require higher specific appreciated that the power drawn by a particular size and
power inputs on scale-up. Indeed, the latter condition is un- type of agitator at a given agitation speed depends firstly on
likely to be produced. These effects can also be shown on that speed; secondly on the aeration and gas recirculation rate
flow maps (Fig 32) (Nienow et al, 1985b). which controls the cavity structure; and thirdly on the bulk
fiow pattern. The importance of these 3 factors decreases in
Multiple turbines the order mentioned but it is the pre-eminence of the agitator
The lower impeller on a stack of Rushton turbines behaves as speed which makes the Michael and Miller correlation ap-
a single impeller on its own provided the impeller spacing parently so successful. The importance of cavities relative to
:T. The upper impellers however all behave similarly but dif- flow ~attem should not be over emphasised.
ferently from the bottom one. Essentially the lower impeller I I I I I I I I I I
Upper impeller N=2'Ss-I~t~/p~
acts as a gas distributor even when it is flooded, so the upper Upper Impeller N=3.25s'lJ I g /n=2
IO _ _ _ ~ _ T ~'-~F,...,..,...,..,..._T
impellers receive less air through them. As a result, they T V Lower rope er N =2"5 s-I- '[ pg [p n=l --
w~e~g'qr-~l~v 0 Lower impeller N=3.25s IJ
flood less easily and draw more power (Fig 35) (Hudcova et
al, 1989)until a speed sufficient to cause gross recirculation
is achieved when all impellers draw equal power (Smith et al,
1987). The latter condition is unlikely to be reached on the
large scale. A rough relationship for the power drawn for
o4- ' 1 ( G)F..=, G.....
multiple impeller systems (Nienow and Lilley, 1979) is
(OG)n=~2 ~ QGI Increasing QO
0-2--
(Pg)n =(Pg/P)bottom +(n-l)P(1-~g) (84) T ~ t i ', I I i I I I I T
o o-o2 oo~ o.o6 o.oa o,~o o.12 o~ o.~6 o,~a 0.20
where Pg/P can be estimated from the Eqs (73) to (78). FI G

Equation (84) will always lead to an over estimate of Pg.

Fig 35. P~JPfor the upper and lower impeller in a dual Rushton
turbine system.

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 24 SPECIALISSUE: FLUID MECHANICSPROBLEMS IN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

Flooding Heat transfer

If possible, a greater air handling capacity especially at the
large scale; and/or a decreased sensitivity to flooding on in-
creasing air flow would be an advantage.
Improved bulk blending
Radial flow agitators tend to give compartmentalization and
other types giving axial flow are able to reduce this tendency,
thus giving better top to bottom blending.
Enhanced gas-liquid mass transfer
This topic is discussed in detail elsewhere in this series of ar-
ticles. Though desirable, it is questionable on theoretical
grounds based on Kolmogoroffs theory of isotropic turbu-
lence whether, for physical absorption of oxygen from air,
any one agitator is better than any other. For example, at the
same (eT)g and superficial gas velocity, Cooke el al (1988)
found 6 impeller types gave equal kLa; whilst Whitton and
Nienow (1993) found equal kLa's at different scales from
0.26 to 2m diameter. Of course, the absolute value of kLa is
very dependent on trace chemicals. Even so, Martin et al
(1994) found that in water, in electrolyte and in water plus
antifoam, though the kLa varied considerably from case to
case, for any one liquid, Rushton turbine and axial flow hy-
drofoils give the same values.
On the other hand, since the absolute value of kLa is so
dependent on trace chemicals, etc, any change in an actual
fermentation due to better bulk blending, lower shear, etc,
may result in a change in kLa. It is probably such effects that
lead to higher kLa's being reported in certain fermentations
after changing agitators (Buckland et al, 1988). On the other
hand, kLa can always be increased by putting in more power,
eg, getting more of the motor power into the broth; or by us-
ing higher aeration rates provided the impeller does not
flood.
On the large scale, the ability to remove heat may be the
critical design requirement (Van't Riet and Tramper, 1991).
Usually, higher heat transfer rates are obtained by large D/T
ratios at equivalent (EET)g (Zhao et al, i993; Cronin and
Nienow, 1989; Cooke etal, 1988).
Lower "shear" rates
A Rushton turbine has traditionally been designated a high
shear impeller (Oldshue, 1981), not generally considered
suitable for fermentations sensitive to high shear stress or
shear rate such as animal cell culture. However, there is still
considerable debate about the phenomena of shear damage
and this topic is discussed in detail elsewhere in this volume.
It is perhaps worth noting here that Rushton turbines have
been used successfully for animal cell culture (Oh et al,
1989) and even at relatively high energy dissipation rates
(Zhang and Thomas, 1993) damage did not occur.
Other very recent work suggests that it is a combination of
local energy dissipation rate in the impeller zone and the fre-
quency of circulation through that zone that determines the
extent of breakdown of mycelia (Justen et al, 1996). The im-
plication of this finding is that damage reduces with increas-
ing scale.
Other radial flow agitators
Rushton turbines with extra blades
Bruin et al (1974) showed that increasing the number of
blades to 12 and 18 on the Rushton turbine increased the
power number to ~7.5 and ~9 respectively and reduced the
fall in aerated power (Fig 36a) as a result of the stabilization
of clinging cavities. In addition, for a given-specific unaer-
ated power input ( e r ) , more air can be handled before
flooding occurs. However, at Reynolds numbers less than
about 1000, 6, 12 and 18 blade impellers all behave similarly
and this advantage is lost (Nienow et a/, 1995) (Fig 36b).

1"2 I 1.2

1.0 I'0 t_
Blades N 2R;;
L,-
6 136
~o 0"8 o 12 122 240
KX X 18 126 250

0.6 0-6
- T
E~
C
0'4 Blades N ~ 0'~
Ib 6 t2s
0"2 o 12 112 - *,
t~ 0"2 at 0.75 W/kg
lit
O la t0s o unaerated
o o
0,0 I o.0 I
0.( 0.1 02 01 0.1 0"
Gas flow number FI G Gas flow n u m b e r FIG

(a) (b)
Fig 36. A comparison of the aerated power draw with 6, 12, and 18 blade Rushton turbines a) in water; b) at low Re (Nienow et al, 1995).

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 Appl Mech Rev vol 51, no 1, January 1998
Hollow blade Rushton turbine.
Van'tRiet et al (1976) first showed that if the 6 flat plates of
the Rushton turbine were replaced by segments of pipe con-
cave in the direction of rotation, the power fall on aeration is
less. This change in power draw is because the transition to
large cavities occurs a t higher aeration rates (Warmoer-
skerken and Smith, 1989). Flooding only occurs at a higher
air flow rate given by
(FIG) F = 2.8Fry (85)
at D/T = 0.4 compared to a constant of 1.2 for Rushton tur-
bines of the same size. There is significant hysteresis and to
recover dispersion after flooding, the air flow must be re-
duced to a value corresponding to a constant of 1.4 in Eq
(85). The unaerated power number is about 3.8.
This impeller is very similar to the Chemineer CD6 which
has blades of semi-circular cross section (Fig 5d). Though
Warmoerskerken and Smith (1989) have claimed higher kLa
values for the hollow blade configuration than with Rushton
turbine (and Chemineer do too for the CD6). Linek et al
(1991) and Dawson (1993) found the same values as with
Rushton turbines and with a range of impellers, respectively.
ICI Gasfoil
The ICI Gasfoii (Cooke et al, 1988) is similar in shape to the
CD6 and Scaba 6SRGT with Po = ~1.8 (T = 30cm) increas-
ing to -2.2 (T = 1.8m) with increasing scale, much like
Rushton turbines (Bujalski et al, 1987). In this case, the aer-
ated power only falls to about 0.9 of the unaerated in water.
Cooke et al (1988) also reported that at the same power in-
puts, whether aerated or unaerated, the Rushton and Gasfoil
gave equal mixing times but both with significant compart-
mentalization compared to axial flow agitators for which 0m
was much shorter. Also, significantly, kLa and hold-up were
reported to be the same for a range of agitators including the
Gasfoil at equal power input and superficial air velocity.
Scaba 6SRGT
This commercial impeller is also similar to the hollow blade
concept and is available with 4 or 6 blades. The 4 blade ver-
sion when aerated is prone to slight torque instabilities (Saito
et al, 1994) so only the latter will be considered here. Fig 37
is a graph of Pg/P versus vvm for the six blade version. The
increase in Pg at flooding is noteworthy as is the independ-
Unaerated po~er./mass = 0"16WIkg
IS7~
|.--00[0
1"2
pg/p I
6SRGT. Po~l'kS
(N=22S rev/min)
0'8
0.6 Rushton'furbine, Po--~5.2
(N = 150 revlminl
0'5
0; I I I I
0.5 1.0 1"5
vVm
Fig 37. P~/P versus QGZ for a Rushton turbine and a Scaba 6SRGT.
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Nienow: Hydrodynamics of stirred bioreactors 25
of Pg on aeration rate at values less than (QG)Fgiving a
ence
PgCPof ~1. This value of 1 results because essentially cavi-
ties do not form behind the blades, air being dispersed as
shown in Fig 38. Thus, since the unaerated power number is
well known (Po ~ 1.45 at Re > l05 in a 0.6m diameter ves-
sel), the aerated power draw can easily be calculated. At an
equivalent power input and impeller size (D/T = 1/3), the
6SRGT is able to handle approximately three times more air
compared to a Rushton before a loaded condition becomes
flooded (Fig 37). Equation (65), applicable to the Rushton
turbine flooding - loading transition can be used for the
Scaba too. Hysteresis at the flooding loading transition is
also found.
Compared to Rushton turbines, hold-up (Saito etal,, 1992)
and kLa values (Shell, 1991) are broadly equivalent at equal
power and superficial air velocities as are mixing times at
equal impeller sizes (Saito e t a l , 1992). In multi-impeller
situations, compartmentalization is found as with all radial
flow impellers.
With increasing viscosity, Pg/P falls somewhat to a value
of about 0.7 at Re z 1000 due to cavity formation (Saito et al,
1992). However, this value is significantly higher than with
12 and 18 blade Rushtons (Nienow et al, 1995) and is main-
tained even in yield stress fluids (Galindo and Nienow, 1993)
though, of course, caverns form.
Axial flow impellers: Downward pumping
Essentially, there are inherent instabilities of flow pattern
with such agitators where the downward flow produced by
the agitator is opposed by the upward flow of the sparged air.
Pitched blade turbines
Pitched-blade turbines pumping downwards are not only li-
able to significant instabilities of flow pattern, they also flood
easily, especially when of low D/T ratio and with a small
projected blade area (Chapman etal, 1983). Thus, 4-bladed
45 pitch turbines exhibit much greater instabilities than 6-
bladed ones. Another way of reducing this tendency is to re-
move the sparger from the small region of reverse flow,
which is the position in which a point sparger would be
placed and put into the downward flow (see Fig 39), ie, use a
ring sparger about 0.8D (Bujaiski etal, 1990). The instability
is linked to the direct loading-indirect loading transition
(Frilink et al, 1984). Thus, at a particular aeration rate, up to
o ~ o
2"0
Fig 38. Gas dispersion from the Scaba impeller.
 26 SPECIALISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

a certain critical speed, air enters directly from the sparger
into the agitator (direct loading) (Fig 39). At and above this
speed, air is driven away from the agitator and only enters it
by recirculation (indirect loading) (Fig 39). Thus, there is a
certain amount of natural instability and of hysteresis in flow
patterns. As a result, torque fluctuations, sometimes very
large, occur in conjunction with them (Chapman et al, 1983).
However, torque instabilities are also linked to the change of
cavity structure from large cavities (Fig 40a) with direct
loading to clinging cavities (Fig 40b) with indirect loading.
At very low aeration rates as might be required in mam-
malian or plant Cell culture, the impact of these instabilities
becomes insignificant. In that case, the low power inputs re-
II Hqainflow
quired to suspend solids, (in this case, cells or microcarriers)
with this impeller under such conditions offers positive ad-
vantages (Chapman et al, 1983).
In addition, the aerated power falls very quickly on aera-
tion to very low values before rising again after flooding
(Cooke et al, 1988; Bujalski et al, 1988). These workers
concluded that except at very low aeration rates, the pitched
blade turbine is unsuitable for bioreactors.
Hydrofoil agitators
Downward pumping hydrofoil agitators might be expected to
exhibit similar hydrodynamic behavior to downward pump-
ing pitched blade turbines. In some respects, this is so
(Cooke et al, 1988). Thus, the 3 bladed Lightnin' A310 and
Chemineer HE3 flood easily (Ibrahim, 1992) though the lat-
ter are often used in combination with CD6s by Chemineer

N
(Myers et al, 1994). Oldshue (1989) introduced the concept
of solidity ratio, ie, the ratio of the projected area occupied
Strong
by the blades of an agitator to the swept area. A value of O. 10
is quoted for an A310. Low values are found for other such
\
Weok flow;
impellers, eg, the Scaba axial hydrofoil impeller which.
Weak flow little or no
dispersion
Cooke et al (1988) found unsuitable for fermentation proc-
(a}
UNDASSED
(bl 11 esses.
DIRECT LOADING INDIRECT LOADING
On the other hand, the Prochem Maxflow T impeller with
Fig 39. Flow patterns with a downward pumping 45 pitched blade its 5 or 6 blades and central hub has a much higher solidity
turbine a) ungassed; b) direct loading; c) indirect loading. ratio (.7_0.95) and the Lightnin A315 has one of ~0.90 and
they have very similar aeration characteristics. However,
some instabilities do occur (Baimer et al, 1987) and they are,
Direction
as with the pitched blade turbines, sensitive to sparger type
and position. An optimum with respect to minimising insta-
bilities and maximising giis handling potential was found to
be a ring sparger Ds = 0.8D with Cs/C = 0.6. For this con-
figuration and with a Maxflo T with D/T ratio of 0.45, the
scale-up equation
Large
~avity ~ ( FI6)cD = 0.03 l(Fr)co L2 (86)
(b) (a)
was found (McFarlane and Nienow, 1995, 1996). For a given
Fig 40. Cavities as viewed from above on a down-pumping pitched aeration rate, operating at speeds greater than given by Eq
blade turbine a) large; b) clinging. (86) ensures conditions at which fluid dynamic and torque
instabilities are minimised.
Water PMO Cs/C: 0,6
The aerated power characteristics are typi-
N : 300 rpm cally (Martin et al, 1994) as shown in Fig 41
P LRS
(-) and depend on both the bulk flows (Fig 42)
~(iii)---q, A s.s and cavity structure (Fig 43). At low aeration
1"0 - - ~ x I ps rates when the impeller is indirectly loaded,
the flow is axially downwards, the cavities
are similar to the vortex ones on Rushton tur-
0 " ~ -- bines and Pg/P only falls to about 0.85. At
high aeration rates, the flow is radial under
(i) direct loading, the cavities are large and Pg/P
0.6- z 0.5 to 0.6. However, unlike the Rushton
turbine, large cavities form most easily at
high speeds because of the importance of re-
0-/,. - J
circulating air in determining their size. Thus,
0 i I I I I i Pg/P is also rather sensitive to agitator speed,
0 1 2 3 ~ 5 6 though the drop in power is less than with
FIG x 10 z (-) Rushton turbines under similar conditions
Fig 4]. Typical aerated power characteristics with a down pumping axial high solidity (Balmer et al, 1987). However, because of
ratio hydrofoil (Prochem Maxflo 7).

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 Appl Mech Rev vol 51, no 1, January 1998 Nienow: Hydrodynamics of stirred bioreactors 27

the sensitivity to recirculation, Pg/P is also sensitive to hold- Cavities can develop. Power falls much more slowly with in-
up, ie, very high hold-ups (due to different liquid physical creasing aeration rate than with downward pumping types
properties) give significantly lower Pg/P values under other- and slower than with Rushton turbines. Fig 44 gives a com-
wise identical conditions (Martin eta/, 1994). All these as- parison (Chapman et al, 1983) of these three cases and Fig
pects makes predictions of power draw of axial flow hydro- 45 some scale-up data for aerated power draw (Bujalski et al,
foils under aerated conditions even more difficult than with 1990) for an up-pumping configuration.
Rushton turbines. At equal (eT)g and Vs, the hold-up with upward-pumping
For single agitators, mixing times for impellers of the 45 pitch blade turbines and Rushton turbines were found to
same size (Haas and Nienow, 1989) are the same when com- be the same even at different scales (Bujalski et al, 1988) and
pared to Rushton turbines whether aerated or unaerated at the kLa values were also the same (Bujalski eta/, 1990).
same energy dissipation rate; and so are kLa values (Martin et If large dense solids are also required to be maintained in
al, 1994) at the same (ET)g and Vs values. suspension, eg, bioleaching applications (Fraser, 1992), this
geometry is much more effective than Rushton turbines or
For multiple impeller configurations (impeller spacing one down pumping pitched blade turbines, especially at high
vessel diameter), the general findings outlined above apply. aeration rates (Bujalski et al, 1988).
For example, PJP is greater than with Rushton turbines but Preliminary work at Birmingham on a new upward
very sensitive to agitator speed and liquid physical properties pumping hydrofoil (APV B-2) indicates that fluid dynamic
(Nienow et al, 1993, 1994). However, the axial flow pattern instabilities are successfully eliminated, Pg/P values are close
reduces the tendency to compartmentalization between dif- to 1, flooding is less likely
ferent impellers but does not eliminate it entirely (Mani-
kowski et al, 1994). Thus, bulk blending is greatly improved to occur and kLa is sus-
(Otomo et al, 1995). On the large scale, the fluid dynamic in- tained (Ozcan-Taskin et al,
stabilities can develop into gross mechanical instabilities, es- 1996). Work at Birming-
pecially in very viscous broths (Nienowet al, 1993, 1994). ham has also shown excel-
lent bulk blending with an
Axial flow agitators: upward pumping up-pumping/down pumping
pair at an aspect ratio of 2
Such a configuration has not been reported in the literature to
(unpublished). (a) Vortex cavity
have been used either in gas-liquid reactors or in bioreactors.
However, studies of pitched blade turbines covering their Ekato intermigs
fluid dynamics, hold-up (Bujalski et al, 1988) and gas-liquid
mass transfer characteristics (Bujalski et al, 1990) indicate The manufacturers recom-
that they are well worthy of consideration. mend that the center part of
the two pumping-directions
Somewhat surprisingly, 45-pitched-blade turbines dis-
agitator should pump up-
perse air extremely well, achieving the flooding-loading tran-
wards. Indeed, flooding
sition and complete dispersion at very low speeds and spe-
occurs much more easily,
cific powers without instabilities. The use of 6 blades, D/T =
1/2, and a sparger ~ 0.8D maximises these advantageous ie, a higher speed and even (b) Clinging cavity
higher power therefore is
trends (Buja!ski et al, 1988). NF is given by required to prevent it, at a
(Fl~)F : 6 x 103(Fr)F2'7(T/To)1"55 (87) particular air rate, if the
center pumps downwards
and NeD by (Dawson, 1993). This find-
( Fl6)co = 12 x 104(Fr)coS(T/To)2"s (88) ing fits in well with the re-
suits for axial flow impel-
where To = lm(see also Eq (29)), Thus, both NF and NeD lers pumping upwards. In
are very insensitive to aeration rates. addition, large spargers are (c) Incipient, large cavity
Even above NCD, clinging cavities are usually present ex- a significant aid to air dis-
cept at the very highest speeds and gassing rates when large persion and sparger di-

osclllal Ion~l ~-~, i ) osclIIBI Ion| t,.)

I lxla| "" - .,~..

/ (d) Large, fully-developed cavity

/ %~,L. ~.

/ Gas-filled cavities,
increasing; N constant
~J .. , Fig 43. Cavity structure on a down
I II In pumping axial high solidity ratio
Fig 42. Bulk flow patterns with a down pumping axial high solidity ratio hydrofoil (Lightnin' A315). hydrofoil (Prochem Maxflo 7).

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 28 SPECIALISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

ameters equivalent to the impeller "wing tips" should be RETROFITTING

used. Pg/P values are generally a little higher than with
Rushton turbines and this parameter, the air dispersion tran-
sition, kLa and hold-up are all relatively insensitive to aera-
tion rate (Dawson, 1993; Dawson et al, 1993).
Air-filled cavities form only on these wing-tips and extend
horizontally from the back of the agitator so that on aeration,
the impeller can be considered a radial flow one. In water,
they increase in size with increasing aeration rate. At very
low rates, cavities can be linked tO each of the tips but with
increasing rates, this ceases and eventually one large cavity
per blade is formed as shown in Fig 46 especially in viscous
broths which are viscoelastic (Fig 46b) (Ozcan-Taskin et al,
1992). Severe vessel vibrations may develop under such
conditions because only two very large cavitids per agitator
are present and as large gas bubbles break away from them,
resonance effects are set up (Kipke, 1982).
Two independently-driven agitators
This concept (Fig 3) is being studied now and some prelimi-
nary results have been reported. Flexibility and greatly re-
duced mixing times are its main attributes to date (Bujalski et
al, 1993; John etal, 1995).
I I
1'0
0"75
In general, there is a surfeit of fermentation facilities in in-
dustry and because of the early emphasis on the use of 1/3 T
Rushton turbines, many contain a set of this type of impel-
lers, typically 3 to 5 on the large scale. Therefore there is
considerable interest in improving their operation, for exam-
ple by retrofitting them with a different agitation system. It
has already been shown here that at the same energy input,
better mixing is achieved by using a larger D/T ratio Rushton
in low viscosity broths (Eq (58)) and in highly viscous shear
thinning ones (Eq (60)). In addition, a higher aeration rate
can be effectively dispersed (Eqs (68),(70)) and a similar
manipulation of Eq (73) shows that vortex and clinging cav-
ity structures are suppressed so that for the same unaerated
power input, Pg/P is greater. Heat transfer rates can also be
enhanced.
Unfortunately, such an increase in the size of a Rushton is
a relatively expensive retrofitting operation, since in order to
use the same power with the larger impeller, the speed must
be reduced in accordance with Eq (21) and therefore the
torque (Eq (22)) must be increased, ie, Ma(D/T) 5/3. This ret-
rofitting therefore probably requires at least a change in
gearbox, seals, steady bearings and shaft diameter. However,
with a lower power number impeller, then equal speed (Eq
I
(20)), torque (Eq (22)) and power (Eqs (21) to (23)) with a
larger impeller can be used if
D/TcxPo 1/5 (89)
for a single impeller or for multiple impellers, with a suffi-
cient spacing between them

O DT 12 r e v l s ) '1
Z~ /,,HFU(3"6revlsl ~ O = T I 2 : T~6 Manipulation of Eq (58) for the turbulence model therefore
O.S ~7 ~HFD (2"7Srevls) shows the mixing, time
I I I Om(ZPo1/15 (91)
0-25 0.5 0.75 1.0
O,~dvv m ) from such a retroft. This reduction is significantly less than
has been previously suggested in the literature (Nienow,
1990a) based on the flow approach which from Eq (36) as-
Fig 44. Comparing Pg/P versus FlG for a Rushton turbine and an
upward and a downward pumping pitched blade turbine. suming FI = constant and Eq (89) gives OmCXPo'6 (see Table
5). Thus, of the impellers discussed here as an alternative to
the Rushton turbine, all but the 12 and 18 blade Rushton's
allow such an enhancement of diameter.
Since air dispersion is inherently from the ventilated cavi-
ties on any impeller, these increases in diameter should also
0.9 L_ ,~ - ~,~,,,,p
~-~ allow higher Pg/P values and better air dispersion for each
agitator relative to its average characteristics as described
0.8 ~ l ~ o
O..
,G
0'7

0-6 f \~\ ~
Tm

0"29
0.5 0"/)S
o 0"61

04, , i ) i I i i i i I , o.)
0 s lo
FI 6 x 102 HIGH v)scoslrY
VISCOELASTIC
Fig 45. Pg/P versus FIG for up-pumping pitched blade turbines of Fig 46. Cavity structure on Intennigs; a) in low viscosity broths; b)
different scales. in high viscosity broths.

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 Appl Mech Rev vol 51, no 1, January 1998
above. For very shear thinning broths, more impellers per
unit height can also be accommodated in this way, compro-
mising between increase in diameter and number. For the
axial hydrofoils, the improved top-to-bottom blending with
multiple impellers is also a significant advantage.
For high viscosity shear thinning broths
kLa ot ~a-"5 (92)
where ~a is given by the Metzner and Otto approach (Cooke
et al, 1988; Dawson et al, 1993; Dawson, 1993). Therefore, a
higher agitator speed gives a higher shear rate which leads to
a lower viscosity and hence a higher kLa. Advantage can be
taken o f this effect only by retrofitting with a new higher
speed drive system and agitator; or, o f course, with the initial
design. However, care must be taken to avoid mechanical
problems with critical speed considerations (King, 1992).
Intermigs are especially capable o f giving such an enhanced
kLa (Dawson et al, 1992) but again the danger o f excessive
vibrations due to resonance with bubbles breaking away from
gas-filled cavities must be recognised (Kipke, 1982).
CONCLUSION
This review shows how the subject has developed in recent
years. It is quite clear that substantial improvements have
been made but in general the level of fluid dynamics in-
volved has not been particularly profound. The reason for
this is almost certainly the complex rheoiogy and multiphase
flows that are generally involved. In addition, the motivation
for improved performance is the ability to increase produc-
tion o f such things as biomass, secondary metabolites and
protein products and hence increase profitability. Whilst it is
commonly recognised that the hydrodynamics affect biopro-
duction processes, the direct linking o f the two has in general
not been proven and ofl:en attempts to improve agitation have
not led to enhanced bio-performance. Undoubtedly, this dis-
appointing result has been due to the poor understanding o f
the hydrodynamics, per se, and even more to the interaction
between agitation and bio-performance (Nienow, 1989). It is
hoped that this article will help to improve this situation in
the future; and also encourage a more in-depth analysis of the
hydrodynamics o f bioreactors which should prove extremely
challenging even to the most advanced practioner working in
more easily defined flows.
Hopefully, computational fluid dynamics, which are men-
tioned in this article here for the first time, will begin to play
a significant role and some early attempts have been made to
do so in recent conferences devoted to bioreactor fluid dy-
namics (Nienow, 1993) and performance (Hjertager and
Marud, 1993). However, it is very early days and the chal-
lenge is very great. For example, the physics of bubble break-
up is not well known, especially in rheologically-complex
fluids with a mycelial solid phase. In addition, the bulk flow
is fully three dimensional and often at transitional Reynolds
numbers with enormously varying local mean velocities, tur-
bulent intensities and energy dissipation rates. The use o f
sliding mesh codes such as that now available from Fluent
should help in that a priori solutions can be obtained. Thus,
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Nienow: Hydrodynamics of stirred bioreactors 29
~one grid rotates with the impeller allowing the zero velocity
condition at its surface to be satisfied whilst it "slides" over
another grid which is stationary to match the vessel wall no-
slip condition (Bakker et al, 1994). Nevertheless, until the
kinetics o f bioprocesses, which are perhaps even more com-
plex than the fluid dynamics, are better understood and capa-
ble o f being modelled computationally too, overall progress
in linking the two interacting aspects which determine the
overall bioperformance, will be severely limited.
ACKNOWLEDGEMENT
The author would like to acknowledge the help o f research
colleagues and technical staff in the (formerly SERC) Center
for Biochemical Engineering, The University o f Birming-
ham, without whom much o f this review could not have been
written, and the BBSRC Chemicals and Pharmaceuticals Di-
rectorate (formerly SERC Biotechnology Directorate) for the
financial support for the research programme on which much
o f it is based.
REFERENCES
Anderson C, Legrys GA, and SolomonsGL (1982), Concepts in the design
of large scale fermenters for viscous culture broths, Chem Eng,
(London1, Feb, 43-49.
Baker MR, Nienow AW, and Emery AN (19881, Mass transfer and power
characteristics of a simulated fermentation broth exhibiting biological
activity, in Proc of 2nd lnt Conf on Bioreactor Fluid Dynamics, R King
(ed/, BHR Group, Cranfield, UK 79-93.
Baker MR (1988), Developmentand application of a biological modelling
fluid for mycelial fermentations, PhD Thesis, Univ of Birmingham, UK.
Bakker A, Fasano JB, and Myers KJ (1994), Effects of flow pattern on the
solids distribution in a stirred tank, in Proc of 8th European Confon
Mixing, I Chem E, Rugby, UK, 1-8.
Balmer GJ, Moore 1PT, Nienow AW (1987), Aerated and unaerated power
and mass transfer characteristics of prochern agitators, in Biotechnology
Processes; Scale-up and Mixing, CS Ho and JY Oldshue (eds), AIChE,
NY, 116-127.
Barnes HA, Hutton JF, and Waiters K (1989), Introduction into Rheology,
Elsevier.
Boger DV (1977), Highly elastic constant-viscosityfluid, J non-Newtonian
Fluid Mech 3, 87-91.
Bongenaar JJTM, Kossen NWF, Metz B, and Meijboom FM (1973),
Method of characterising the rheological properties of viscous fermen-
tation broths, Biotech Bioeng 15, 201-206.
Brodkey RS (1975), Mixing in turbulent fields, in Turbulence in Mixing
and Reaction, RS Brodkey(ed), Academic Press, NY.
Bruin W, Van't Riet K, and Smith JM (19741, Power consumption with
aerated Rushton turbines, Trans1 Chem E 52, 88.
Buckland BC, Gbewonyo K, DiMasi D, Hunt G, Westerfield G, and
Nienow AW (1988), Improved performance in viscous mycelial fer-
mentations by agitator retrofitting, Biotech Bioeng 31,737-742.
Bujalski W (1987), Three phase mixing : studies of geometry, viscosity and
scale, PhDThesis, Univ of Birmingham, UK.
Bujalski W, Konno M, and Nienow AW (1988), Scale-up of 45 pitch-blade
agitators for gas dispersion and solid suspension, in Proc of 6th Euro-
pean Mixing ConS Italy; A1DIC/BHRGroup Fluid Engineering, Cran-
field, UK, 389-398.
Bujalski W, Nienow AW, and Liu Huoxing (1990) Use of upward pumping
45 pitched blade turbine impellers in 3-phase reactors, Chem Eng Sci
45, 415-421.
Bujalski W, Nienow AW, Chatwin S, and Cooke M (1986), Dependencyon
scale and material thickness of power numbers of different impeller
types, in Proc oflnt Confon Mechanical Agitation, ENS Ass of Chem
Eng, Toulouse; 1-37 to 1-46.
Bujalski W, Nienow AW, Chatwin S, and Cooke M (1987), Dependencyon
scale of power numbers of Rushton disc turbines, Chem Eng Sci 42,
317-326.
Bujalski W, Sharpe R, KoutsakosE, NienowAW, Sanchez A, Torres L, and
Galindo E (1993), Preliminary investigations of the mixing performance
 30 SPECIALISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY
of an independently-driven dual impeller fermenter, in 1993 Institution
of Chemical Engineers, I Chem E, Rugby, UK, 678-680.
Calabrese RV, and Stoots CM, (1989), Flow in the impeller region of a
stirred tank, Chem Eng Prog, May, 43-50.
Chapman CM, Nienow AW, Cooke M, and Middleton JC (1983), Particle-
gas-liquid mixing in stirred vessels, Chem Eng Res Des 61, 71-81, 82-
95, 167-181,182-185.
Chapman CM, Nienow AW, and Middleton JC (1980), Surface aeration in
a small agitated and sparged vessel, Biotech Bioeng 22, 981-994.
Cheng DC-H (1979), Role of extensional flows in fluid mixing and disper-
sion, in Proc of 3rd European Mixing Conf, BHR Group, Cranfield,
UK, 73-90.
Cooke M, Middleton JC, and Bush JR (1988), Mixing and mass transfer in
filamentous fermentations, in Proc of 2nd lnt Conf on Bioreactor Fluid
Dynamics, R King (ed), BHR Group, Cranfield, UK, 37-64.
Corrsin S (1964), Isotropic turbulent mixer: Part II: Arbitary Schmidt num-
ber, A1ChEJ 9, 870-877.
Cronin DG, and Nienow AW (1989), Mixing studies in a large laboratory
proto-fermenter: Rushton turbines, in Proc of 3rd Bioreactor Project
Res Syrup. GW Moody (ed), Natl Eng Lab, E Kilbfide, UK, 17-34.
Cronin DG, Nienow AW, and Moody GW (1994), Experimental study of
the mixing in a proto-fermenter agitated by dual Rushton turbines, Food
and Bioproducts Processing, (Trans Institution of Chemical Engineers,
Part C), 72, 35-40.
Cutter LA (1966), Flow and turbulence in a stirred tank, AIChEJ 12, 35-44.
Davies JT (1985), Drop sizes of emulsions related to turbulent energy dissi-
pation rates, Chem Eng Sci 40, 839-842.
Dawson MK (1993), Influence of agitator type on fluid dynamics and oxy-
gen mass transfer in a pilot scale vessel, PhD Thesis, Univ of Birming-
ham, UK.
Dawson MK, Nienow AW, and Moody GW (1993), Comparison of Inter-
mig and Rushton turbine gas-liquid mass transfer in a pilot scale mixing
vessel, in The 1993 Institution of Chemical Engineers Research Event, I
Chem E, Rugby, UK, 645-647.
Dyster KN, Koutsakos E, Nienow AW,and Jaworski Z (1993), LDA steady
of the radial discharge velocities generated by a Rushton turbine: New-
tonian fluids, Re >_5, Chem Eng Res Des 71, 11-23.
Elson TP (1988), Mixing of fluids possessing a yield stress, in Proc of 6(h
European Mixing ConJ~ Italy, AID1C/BHR Group, Cranfield, UK, 485-
492.
Elson TP, Solomon J, Nienow AW, and Pace GW (1982), Intei-action of
yield stress and viscoelasticity on the Weissenberg effect, J Non-
Newtonian Fluid Mech 11, 1-22.
Elson TP, Cheesman DJ, and Nienow AW (1986), X-ray studies of cavern
sizes and mixing performance with fluids possessing a yield stress,
Chem Eng Sci 41, 2555-2562.
Evangelista JJ, Katz S, and Shinnar R (1969), Scale-up criteria for stirred
tank reactors, AIChEJ 15, 843-853.
Fraser G (1992), Gas dispersion and mixing for mineral oxidation reactors,
in Proc of Extractive Metallurgy of Gold and Base Metuls, Australian
Institute of Mining and Metallurgy, 293-301.
Frijlink JJ, Kolijn M, and Smith JM (1984), Suspension of solids with aer-
ated pitched blade turbines in Fluid Mixing H, 1 Chem E Symp Ser, No
89, 49-58,.
Galindo E, Nienow AW, and Badham RS (1988), Mixing of simulated
Xanthan gum broths, in Proc of 2nd lnt Conf on Bioreactor Fluid Dy-
namics, BHR Group, Cranfield, UK, 65-78.
Galindo E, and Nienow AW (1992), Mixing of highly viscous simulated
Xanthan fermentation broths with the Lightnin' A315 impeller, Biotech
Prog 8, 233-239.
Galindo E, and Nienow AW (1993), Performance of the Scaba 6SRGT agi-
tator in the mixing of simulated Xanthan gum broths, Chem Eng Tech
16, 102-108.
Geisler R, Krebs R, Forschner P (1994), Local turbulent shear stress in
stirred vessels and its significance for different mixing tasks, in Proc of
8th European Confon Mixing, I Chem E, Rugby, UK, 241-251.
Groen DJ, van der Laan RGJM, and Luyben KChAM (1993), Scale depend-
ence of mixing in bioreactors, in Proc of lnt Symp on Bioreactor Per-
Jbrmance, U Mortensen and HJ Noorman (eds), Biotechnology Re-
search Foundation, Lurid, Sweden, 79-84.
Grenville R, Ruszkowski S, and Garred E (June 1995), Blending of miscible
liquids in the turbulent and transitional regimes, N Am Mixing Conf,
Banff, Canada,.
Harnby N, Edwards MF, and Nienow AW, (eds) (1992), Mixing in the
Process Industries, 2nd Ed, Butterworths Heinemann, London.
Hass VC and Nienow AW (1989), New axial pumping agitator for the dis-
persion of gas in liquids, Chem lng Tech 61,152-154 (in German).
Herbert RM, Knobling K, and Post T (1994), Quick estimation of mixing
time, in Chemie Tech 23, 40-41 (in German).
Downloaded From: http://appliedmechanicsreviews.asmedigitalcollection.asme.org/ on 08/16/2016 Terms of Use: http://www.asme.org/about-asme/terms-of-use
Appl Mech Rev vol 51, no 1, January 1998
Hirata Y, Moore IPT, and Nienow AW(1994), Estimation of cavern sizes in
a shear-thinning plastic fluid agitated by a Rushton turbine based on
LDA measurements, J Chem Eng, Japan 27, 235-237.
Hjertager BH and Morud K (1993), Computational fluid dynamics simula-
tion of bioreactors, in Proc of lnt Syrup on Bioreactor Performance, U
Mortensen and HJ Noorman (eds), Biotechnology Research Foundation,
Lund, Sweden, 47-61.
Hudcova V, Machon V, and Nienow AW (1989), Gas-liquid dispersion
with dual Rushton turbine impellers, Biotech Bioeng 34, 617-628.
lbrahim SB (1992), Comparative study of impeller performance in solid-
gas-liquid mixing, PhD Thesis, Univ of Birmingham, UK.
Ibrahim SB and Nienow AW (1995), Power curves and flow patterns for a
range of impellers in Newtonian fluids; 40<Re<5xl0 s, Chem Eng Res
Des, (Trans I Chem E Part A) 73,485-491.
Jahoda M, Pinelli D, Nocentini M, Fajner D, Magelli F, and Machon V
(1994), Homogenization of liquids and fluid-dynamic behavior of ves-
sels stirred with multiple axial impellers, in Proc of Sth European Mix-
ing ConS I Chem E, Rugby, UK, 113-120.
Jahoda M and Machon V (1994), Homogenization of liquids in tanks stirred
by multiple impellers, Chem Eng Tech 17, 95-101.
Jaworski Z, Nienow AW, Koutsakos E, Dyster KN, and Bujalski W (1991),
LDA study of turbulent flow in a bafffled vessel agitated by a pitched
blade turbine, Chem Eng Res Des 69, 313-320.
.laworski Z and Nienow AW (1994), LDA measurements of flow fields with
hydrofoil impellers in fluids with different rheological properties, in
Proc of Sth European Mixing Conf, I Chem E, Rugby, UK, 105-112.
Jaworski Z, Pacek AW, and Nienow AW (1994), Flow close to cavern
boundaries in yield stress fluids, Chem Eng Sci 49, 3321-3324.
John AH, Bujalski W, and Nienow AW (1995), Investigations into the per-
formance of an independently driven, dual impeller proto-fermenter :
mixing times, in The 1995 Institution of Chemical Engineers Research
Event, I Chem E, Rugby, UK, 710-712.
Justen P, Paul GC, Nienow AW, and Thomas CR (1996), Dependence of
mycelial morphology on impeller type and agitation intensity, Biotech
Bioeng, accepted.
Khang SJ and Levenspiel O (1976), New scale-up and design criteria for
stirrer agitated batch mixing vessels, Chem Eng Sci 31,569-577.
King R (1992), Mechanical aspects of mixing, in Mixing in the Process In-
dustries, N Hamby, MF Edwards and AW Nienow (eds), 2nd Ed, But-
terworth-Heinemann, London, 250-293.
Kipke K (1982), Fluid Ioadings on impellers and tanks in gassed liquids, in
Proc of 4th European Mixing Conf, BHRA Fluid Engineering, Cran-
field, UK, 355-370.
Koutsakos E, Nienow AW, and Dyster KN (1990), Laser anemometry study
of shear thinning fluids agitated by a Rushton turbine, in Fluid Mixing
IV, 1 Chem E Syrup Ser No. 121, 51-74.
Kuboi R and Nienow AW (1986), Intervortex mixing rates in high viscosity
liquids agitated by high speed dual impellers, Chem Eng Sci 41, 123-
134.
Kuboi R, Nienow AW, and Allsford K (1983), Multipurpose stirred tank
facility for flow visualization and dual impeller power measurement,
Chem Eng Comm 22, 29-39.
Levich VG (1962), Physico-chemical hydrodynamics, Prentice Hall, USA.
Linek V, Benes P, and Sinkule J (1991), Hollow blade agitator for mass
transfer in gas-liquid bioreactors, Trans Institution of Chemical Engi-
neers Research Event, Part C 69, 145-148.
Machon V, McFarlane CM, and Nienow AW (1992), Power input and gas
hold-up in gas liquid dispersions agitated by axial flow impellers, in
Fluid Mechanics of Mixing, R King (ed), Kluwer, Netherlands, 91-98.
Manikowski S, Bodemeier A, L0bbert A, Bujalski W, and Nienow AW
(1994), Measurement of gas and liquid flows in stirred tank reactors
with multiple agitators, Can J Chem Eng 72, 769-781.
Mann U and Rubinovitch M (1994), Measuring local flow rates in process
units, lnd Eng Chem Process Des Dev 22,545-547.
Martin T, McFarlane CM, and Nienow AW (1993), Effect of coalescence
inhibitions on impeller performance in gas-liquid systems, in The 1993 1
Chem E Research Event, I Chem E, Rugby, UK, 648-650.
Martin T, McFarlane CM, and Nienow AW (1994), Influence of liquid
properties and impeller type on bubble coalescence behavior and mass
transfer in sparged, agitated bioreaetors, in Proc of 8th European Mix-
ing Conf, 1 Chem E, Rugby, UK, 57-64.
Mayr B, Nagy E, Horvat P, and Moser A (1994), Scale-up on basis of
structured mising models: a new concept, Biotech Bioeng 43, 195-206.
McFarlane CM and Nienow AW, Fluid dynamic studies of high solidity ra-
tio hydrofoil impellers in aerated bioreactors: a review and recent re-
sults, Biotech Prog, Part 1-1V 11, 601-618 (1995) 12, 1- 15 (1996).
Metz B, Kossen NW, and Suijdam JC (1979), Adv Biochem Eng 11,104.
 Appl Mech Rev vol 51, no 1, January 1998
Metz B, de Bruijn EW, and van Suidam JC (1981), Method for quantitative
representation of the morphology of molds, Biotech Bioeng 23, 149-
162.
Metzner AB and Otto RE (1957), Agitation of non-Newtonian fluids;
AIChEJ3, 3.
Michel BJ and Miller SA (1962), Power requirements of gas-liquid agitated
systems, AIChEJ g, 262.
Myers KJ, Fasano JB, and Bakker A (1994), Gas dispersion using mixed
high efficiency/disc impeller systems, in Proc ofgth European Confon
Mixing, 1 Chem E, Rugby, UK, 65-72.
Nienow AW (1968), Suspension of solid panicles in turbine agitated baffled
vessels, Chem Eng Sci 23, 1453-9.
Nienow AW (1984), Mixing studies on high viscosity fermentation proc-
esses - Xanthan gum, in World Biotechnology Report 1984, Vol 1,
Europe, Online (London), 293-304.
Nienow AW (1989), Stirred bioreactors: facts or fiction, Chem Engineer
459, 73-75,.
Nienow AW (I 990a), Agitators for mycelial fermentations, Trends in Bio-
tech 8, 224-233.
Nienow AW (1990b), Gas dispersion performance in fermenter operation,
Chem Eng Prog 86, 61-71.
Nienow AW (1991 ), Aeration-biotechnology, Kirk Othmer Encyclopedia of
Chemical Technology, 4th Ed, Wiley, New York, Vol 1,645-660.
Nienow AW (ed) (1993), Proc of 3rd Int Conf on Bioreactor and Bioproc-
ess Fluid Dynamics. BHR Group/MEP, London.
Nienow AW, Buckland BC, and Hunt G (19945, Fluid dynamic study of the
retrofitting of large bioreactors : turbulent flow, Biotech Bioeng 44,
1177-1186.
Nienow AW and Elson TP (1988), Aspects of. mixing in theologically-
complex fluids, Chem Eng Res Des 66, 5-15.
Nienow AW, Kendall S, Moore IPT, Ozcan-Taskin NG, and Badham RS
(1995), Characteristics of aerated twelve and eighteen blade Rushton
impellers at transition Reynolds numbers, Chem Eng Sci 50, 593-599.
Nienow AW, Konno M, and Bujalski W (1985a), Studies on three-phase
mixing; a review and recent results, in Proc of 5th European Mixing
Conf, BHRA Fluid Engineering, Cranfield, UK, 1-13.
Nienow AW and Lilly AW (1979), Power drawn by multiple impellers in
sparged, agitated vessels, Biotech Bioeng 21, 2241-2245.
Nienow AW, Liu Huoxing, Wang Haozhung, Allsford KV, Cronin D, and
Hudcova V (1988), Use of large ring spargers to improve the perform-
ance of fermenters agitated by single and multiple standard Rushton
turbines, in Proc of 2nd lnt Conf on Bioreactor Fluid Dynamics,
BHRA, Fluid Engineering Centre, Cranfield, UK, 159-177.
Nienow AW, Middleton JC, and Chapman CM (1979), Gas recirculation
rate through impeller cavities and surface aeration in sparged, agitated
vessels, Chem Eng,117, 111-8.
Nienow AW and Miles D (19785, Effect of impeller/tank configurations on
fluid-particle mass transfer, Chem Eng J 15, 13-24.
Nienow AW and Ulbrecht JJ (1985), Gas-liquid mixing in high viscosity
systems, in Mixing of Liquids by Mechanical Agitation, JJ Ulbrecht and
GK Patterson (eds), Gordons and Breach, New York, 203-235.
Nienow AW, Warmoeskerken MMCG, Smith JM, and Konno M (1985b),
Flooding/loading transition and the complete dispersal condition in aer-
ated vessels agitated by a Rushton turbine, in Proc of 5th European
Mixing Conf, Germany, BHRA Fluid Engineering, Cranfield, 153-154.
Nienow AW, Weetman RJ, Hunt G, and Buckland BC (1993), Fluid dy-
namic study of the retrofitting of a large pilot scale agitated bioreactor,
in Proc of 3rd lnt Conf on Bioreactor and Bioprocess Fluid Dynamics,
AW Nienow (ed), BHR Group/MEP, London 505-519.
Nienow AW and Wisdom DJ (1974), Flow over disc turbine blades, Chem
Eng Sci 29, 1994-7.
Nienow AW, Wisdom DJ, and Middleton JC (1978), Effect of scale and
geometry on flooding, recirculation and power in gassed, stirred vessels,
in Proc of 2nd European Conf on Mixing, BHRA Fluid Engineering,
Cranfield, F I- I-F 1- 16 and discussion, X53-X55.
Nienow AW, Wisdom DJ, Solomon J, Machon V, and Vlcek J (1983), Ef-
fect of rheological complexities on power consumption in an aerated
agitated vessel, Chem Eng Comm 19, 273-293.
Oh SKW, Nienow AW, AI-Rubeai M, and Emery AN (1989), Effect of
agitation intensity with and without continuous sparging on the growth
and antibody production of hybridoma cells, ,1Biotech 12, 45-62.
Oldshue JY (I 981 ), Fluid Mixing Technology, McGraw Hill, NY.
OtomoN, Bujalski W, and Nienow AW (1993), Mixing time measurements
for an aerated single- and double-impeller stirred vessel by using a con-
ductivity technique, in The 1993 Institution of Chemical Engineers Re-
search Event, I Chem E, Rugby, UK, 669-671.
Otomo N, Bujalski W, and Nienow AW (1995), Application of a compart-
ment model to a vessel stirred with either dual radial or dual axial flow
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Nienow: Hydrodynamics of stirred bioreactors 31
impellers, in The 1995 Institution of Chemical Engineers Research
Event, I Chem E, Rugby, UK, 829-831.
Ozcan-Taskin NG, Badham RS, Dyster KN, Jaworski Z, Moore IPT,
Nienow AW, Wyszynski M, and MeKemmie J (19965, Gas dispersion
performance of a newly designed impeller in the transitional regime, in
The 1996 Institution of Chemical Engineers Research Event, I Chem E,
Rugby, UK, 880-882.
Ozcan-Taskin NG, Nienow AW, and Chatwin S (1992), Les characteris-
tiques de puissance des lntermigs et des turbines Rushton dans les flu-
ides viscoelastiques a viscosite constante, in Agitation Industrielle, J
Bertrand (ed), Lavoisier Technique et Documentation, Paris, France, 11-
10 to 11-17.
Ozcan NG, Decloux M, and Bruxelmane M (1990), Effect of viscosity on
cavity formation and power characteristics of an agitated, aerated New-
tonian fluid, Chem Eng Res Des 68, 63-68.
Ruszkowski S (1994), Rational method for measuring blending perform-
ance and comparison of different impeller types, in Proc ofgth Euro-
pean Mixing Conf, I Chem E, Rugby, UK, 283-291.
Saito F, Nienow AW, Chatwin S, and Moore IPT (1992), Power, gas disper-
sion and homogenization characteristics of Scaba SRGT and Rushton
turbine impellers, J Chem Eng, Japan 25, 281-287.
Seichter P, Mazoch J, and Slama V (19925, Scale-up of power input in gas-
liquid systems with multiple stirrers, in Agitation lndustrielle, J Ber-
trand (ed), Lavoisier Technique et Documentation, Paris, France, II-18
to II-25.
Shaw JA (1994), Understanding the effects of impeller type, diameter and
power on mixing time, Chem EngProg, Feb, 45-48.
Shell (1992), private communication, Comparison of Scaba 6SRGT and
Rushton turbine mass transfer data.
Singh V and Constantinides A (1988), Use of mass transfer and mixing cor-
relations for the modelling of oxygen transfer in stirred tank fermentors,
in Proc of 2nd lnt Conf on Bioreactor Fluid Dynamics, BHR Group,
Cranfield, UK, 95-115.
Singh V, Hensler W, Fuchs R, and Constantinedes A (19865, On-line de-
termination of mixing parameters in fermentors using pH transients, in
Proc of lnt Conf on Bioreactor Fluid Dynamics, BHR Group, Cranfield,
UK, 231-256.
Sinovic V, Kuboi R, and Nienow AW (19865, Power numbers, Taylor num-
bers and Taylor vortices in non-Newtonian fluids, Chem Eng Sci 41,
2915-2923.
Smith JM, Warmoeskerken MMCG, and Zeef E (1987), in Biotechnology
Processes; Scale-up and Mixing, CS Ho and JY Oldshue (eds), AIChE,
NY, 107-115.
Solomon J, Nienow AW, and Pace GW (1981a), Flow patterns in agitated
plastic, and pseudoplastic viscoelastic fluid, in Fluid Mixing, 1 Chem E
Symp Series, No 64, A 1-A 13.
Solomon J, Nienow AW, Elson TP, and Pace GW (1981b), Cavern sizes in
agitated fluids with a yield stress, Chem Eng Comm 11, 143-164.
Sweere APJ, Meesters JR, Luyben KCAM, and Kossen NWF, in Proc oflnt
Confon Bioreactor Fluid Dynamics, BHR Group, Cranfield, UK, 1986,
217-230.
Takahashi Koji and Nienow AW (19925, Effect of gas density on power
consumption in an aerated vessel agitated by a Rushton turbine, .1 Chem
Eng, Japan, 25, 432-434.
Tatterson GB (1991), Fluid Mixing and Gas Dispersion in Agitated Tanks,
McGraw Hill, NY.
Tatterson GB, Yuan HHS, and Brodkey RS (19805, Stereoscopic visualiza-
tion of the flows for pitched blade turbines, Chem Eng Sci 35, 1369-
1375.
Torrestiana B, Galindo E, Nienow AW, and Zhao Xueming (1991), In-
fermenter power measurement during a Xanthan gum fermentation
compared with non-fermentative studies, Food and Bioprod Proc
(Trans I Chem E, Part C) 69, 149-155.
Vasconcelos JMT, Alves SS, and Barata JM (1994), Mixing in gas-liquid
contactors agitated by multiple turbines - I: Structured model, Chem
Eng Sci 50, 2343-2354.
Van Suidam JC and Metz B (19815, Influence of engineering variables upon
the morphology of filamentous molds, Biotech Bioeng 23, 111-148.
Van Suidam JC and Dusseljee PJB (1987), in Physical Aspects of Bioreac-
tor Performance, W Crueger (ed), Dechema, Frankfurt, 107-120.
Van't Riet K and Smith JM (1975), Trailing vortex system produced by
Rushton turbine agitators, Chem Eng Sci 30, 1093.
Van't Riet K and Tramper J (1991), Basic Bioreactor Design, Marcel
Dekker, NY.
Van't Riet K, Boom JM, and Smith JM (1976), Power consumption, im-
peller coalescence and recirculation in aerated vessels, Trans 1 Chem E
54, 124-131.
Walters K (1975), Rheometry, Chapman and Hall, London.
 32 SPECIALISSUE: FLUIDMECHANICSPROBLEMSIN BIOTECHNOLOGY Appl Mech Rev vol 51, no 1, January 1998

Warmoeskerken MMCG and Smith JM (1989), Hollow blade agitator for
dispersion and mass transfer, Chem Eng Res Des 67, 193-198.
Weetman RJ and Oldshue JY (1988), Power, flow and shear characteristics
of mixing impellers, in Proc of 6th European Mixing Conf, Italy,
AIDIC/BHR Group, Cranfield, UK, 43-50.
Weetman RJ and Coyle CK (1989), Use of fluid foil impellers in viscous
mixing applications, paper to AIChE meeting.
Whitton MJ and Nienow AW (1993), Scale-up correlations for gas hold-up
and mass transfer coefficients in stirred tank reactors, in Proc of3rd lnt
Conf on Bioreactor and Bioprocess Fluid Dynamics, AW Nienow (ed),
BHR Group/MEP. London, 135-145.
Wu H and Patterson GK (1989), Laser-doppler measurements of turbulent
flow parameters in a stirred mixer, Chem Eng Sci 44, 2207-222 I.
Zhao Xueming, Nienow AW, Kent CA, Chatwin S, and Galindo E (1992),
Improving Xanthan fermentation performance by changing agitators, in
Fluid Mechanics of Mixing, R King (ed), Kluwer, Nederlands, 277-285.
Zhang Z, Ferenczi, MA, and Thomas CR (1992), Micromanipulation tech-
nique with a theoretical cell model for determining mechanical proper-
ties of single mammalian cells, Chem Eng Sci 47, 1347-1354

Alvin Nienow is the Director of the Centre for Biochemical

Engineering at the University of Birmingham (UK) and Profes-
sor in the School of Chemical Engineering. He is a Fellow of
the Royal Academy of Engineering and of the Institution of
Chemical Engineers. He studied at University College London
from where he received a PhD (1968) and a higher doctorate
(1980). He is the author of over 180 archival articles on many
aspects of mixing and is an editor of the book Mixing in the
Process Industries, now in its 2nd edition. He was awarded the
Moulton Medal of the Institution of Chemical Engineers in
1984 for a four part series of papers entitled Particle-Gas-
Liquid Mixing in Stirred Vessels. His other research area of
interest is fluidization (~ 50 papers). In 1993, he was awarded the Jan E Purkyne
Medal of the Academy of Sciences of the Czech Republic for services to Czech chemi-
cal engineering. Outside work, he enjoys sports, jazz, dancing, and travel

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