Eng. Life Sci. 2017, 17, 500–511 www.els-journal.

com

Stephan C. Kaiser1 Research Article

Sören Werner2
Valentin Jossen2 Development of a method for reliable power
Matthias Kraume3
Dieter Eibl2
input measurements in conventional and
single-use stirred bioreactors at laboratory
1
Finesse Solutions Inc., Santa
Clara, USA
scale
2
Institute of Chemistry and
Biotechnology, Zurich University Power input is an important engineering and scale-up/down criterion in stirred
of Applied Sciences, Wädenswil, bioreactors. However, reliably measuring power input in laboratory-scale systems
Switzerland is still challenging. Even though torque measurements have proven to be suitable
3
in pilot scale systems, sensor accuracy, resolution, and errors from relatively high
Technische Universität Berlin,
levels of friction inside bearings can become limiting factors at smaller scales. An
Fachgebiet Verfahrenstechnik,
experimental setup for power input measurements was developed in this study
Berlin, Germany
by focusing on stainless steel and single-use bioreactors in the single-digit volume
range. The friction losses inside the air bearings were effectively reduced to less than
0.5% of the measurement range of the torque meter. A comparison of dimensionless
power numbers determined for a reference Rushton turbine stirrer (NP = 4.17 ±
0.14 for fully turbulent conditions) revealed good agreement with literature data.
Hence, the power numbers of several reusable and single-use bioreactors could
be determined over a wide range of Reynolds numbers between 100 and >104 .
Power numbers of between 0.3 and 4.5 (for Re = 104 ) were determined for the
different systems. The rigid plastic vessels showed similar power characteristics
to their reusable counterparts. Thus, it was demonstrated that the torque-based
technique can be used to reliably measure power input in stirred reusable and single-
use bioreactors at the laboratory scale.
Keywords: Measurement / Power input / Single-use bioreactors / Stirrers / Torque
Received: April 8, 2016; revised: October 8, 2016; accepted: October 20, 2016

DOI: 10.1002/elsc.201600096

1 Introduction most single-use bioreactors are agitated by specially designed im-

pellers making it difficult to compare them with their reusable
Power input (or volumetric power input) is one of the most im- counterparts.
portant engineering and scale-up criteria for bioreactors, since As described in the review by Ascanio et al. [9], temperature-
it is related to most unit operations, such as mixing, gas disper- and torque-based measurement techniques prevail over others,
sion, gas–liquid mass transfer, heat transfer, and solid suspen- something which is also confirmed by Table 1 that summarizes
sion [1–3]. Furthermore, power input is associated with hydro- some studies on power measurements described in the litera-
dynamic stress, which may affect cell growth and/or productivity ture [10–37]. Even though this overview is far from complete, it
of shear-sensitive production organisms [4–6]. However, unlike is obvious that the majority of these studies focused on standard
pilot and production scale agitators, only limited data on power stirrers, such as Rushton turbines [10–24], pitched blade im-
input in laboratory-scale bioreactors are available, in particular pellers [10, 15, 20, 23, 25–27], curved blade impellers [12, 21, 24],
for single-use bioreactors. In contrast to their reusable counter- or more modern stirrers, such as SCABA [14, 28] and Light-
parts, these systems are delivered by the manufacturers that are nin [16, 19, 27, 29–31] impellers. These are commonly used for
preassembled, sterilized, and ready to use [7, 8]. Furthermore, agitation in baffled, flat-bottomed tanks. In fact, only one experi-
mental study on power input investigations in single-use bench-
top bioreactors was found [32], where the Mobius CellReady
Correspondence: Dr. Stephan C. Kaiser ([email protected]), Fi- 3L, the UniVessel 2L SU, and the BioBLU 5L (formerly known
nesse Solutions Inc., 3501 Leonard Court, Santa Clara, CA 95054, as CelliGen BLU) were investigated for a few operational con-
USA ditions that only examined water-like viscosities with Reynolds
Abbreviations: CFD, computational fluid dynamics numbers in excess of 3.5 × 103 [32]. This means that most
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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and
distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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Table 1. Examples of power input measurements described in the literature

Geometrical details

System/stirrer VL (L) D (m) d/D (−) Flow regime (Re) Ref.

Load cell Rushton turbine and curved blade 50 0.40 0.33 Turbulent (8.86 × 104 –2.72 × 105 ) [24]
impellers in baffled,
flat-bottomed, cylindrical vessel
Electrical power Minibioreactor with triple Rushton 0.007 0.016 0.44 Transition–turbulent (1 × 103 –6 × 103 ) [33]
turbine
Four-bladed 45° pitched-blade and 570 0.90 0.34 Turbulent (2.5 × 105 –7 × 105 ) [26]
flat-blade impellers in a
flat-bottomed, baffled mixing
tank
Rushton turbine, Prochem Maxflo 600 0.82 0.37–0.50 Transition–turbulent (300–106 ) [19]
T, and Lightnin A-315 in
fermentor tank
Strain gauge Rushton turbine, Smith turbine, 2.5 0.147 0.33 Transition–turbulent (100–8 × 104 ) [15]
pitched blade impellers in
baffled vessel
Two-stage four flat-blade turbines 8 0.21 0.40 Transition–turbulent (300–9 × 104 ) [34]
in unbaffled, flat-bottomed
cylindrical vessel
Lightnin A-315 impeller in 72 0.45 0.49 Laminar–low turbulent (1–103 ) [29]
flat-bottomed cylindrical vessel
with baffles
Xanthan fermentation with 130 0.49 0.33–0.54 Turbulenta) (1.63 × 106 –5.72 × 106 ) [28]
Rushton turbines, Prochem
Maxflo T or SCABA 6SRGT
impellers
Prochem Maxflo T and Lightnin 135 0.56 0.40–0.51 Turbulentb) (105 –6.4 × 106 ) [30]
A315 in baffled, cylindrical,
flat-bottomed vessel
Rushton turbine, Smith turbine, 170 0.60 0.33 Turbulent (3 × 104 –2 × 105 ) [20]
pitched blade turbine, and
propeller in baffled, cylindrical
flat-bottomed vessel
Rushton turbine, 45° pitched blade 175 0.61 0.33 Turbulentb) (9.6 × 104 –3.15 × 106 ) [25]
impellers in baffled vessel
Four-blade and six-blade Scaba 175 0.61 0.33 Transition–turbulent (103 –06 ) [14]
SRGT impellers and Rushton
turbine in flat-bottomed,
baffled, cylindrical vessel
Rushton turbine, Smith turbine, 200 0.634 0.33 Turbulent (9.5 × 104 –2.52 × 105 ) [31]
Lightnin A315 in flat-bottomed,
baffled, cylindrical vessel
One or two 6-bladed disc turbines 280–560 0.72 0.33 Turbulent [22]
in baffled, cylindrical vessel
under aeration
Dynamometer Baffled minibioreactor with 0.1 0.06 0.33 Transition–turbulent (2 × 103 —1.3 × 104 ) [35]
Rushton turbine
6-blade disk turbines, 2-blade flat 2.5 / 20 0.15–0.30 0.25–0.75 Low-to-medium turbulent (6 × 103 –105 ) [10]
paddles, and 4-bladed 45° pitch
turbines in baffled,
flat-bottomed, cylindrical vessels
Rushton turbine in flat-bottomed, 6.5 0.205 0.52 Transition–turbulent (2 × 103 –105 ) [17]
cylindrical vessel with baffles
Rushton turbine, six-bladed 19 0.29 0.33–0.60 Laminar–turbulent (40–105 ) [16]
pitched turbine, EKATO
Intermig, Lightnin A-310, and
Chemineer HE-3 in baffled
cylindrical vessel
(Continued)


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Table 1. Continued.

Geometrical details

System/stirrer VL (L) D (m) d/D (−) Flow regime (Re) Ref.

Rushton turbine, pitched-blade 20 0.288 0.33–0.73 Turbulent [36]

turbine, MIXEL-TT propeller,
MIXEL-TTP propeller,
two-stage EKATO INTERMIG
in baffled cylindrical vessel with
conical-shaped bottom
Torque meter Minibioreactor with hollow-shaft 0.012 0.7 Laminar–turbulent (103 –1.1 × 104 ) [37]
gas inducing blade impellerc)
Rushton turbine in flat-bottomed 0.6–18.7 0.09–0.288 0.5 Laminar–transition (1–400) [13]
cylindrical vessels
Mobius CellReady 3L, UniVessel 1.5–3.5 0.13–0.17 0.42–0.59 Transition–turbulent (3.5 × 103 –3.3 × 104 ) [32]
SU 2L and 5L CelliGen BLU
disposable and 2L glass
bioreactor
Rushton turbine & concave blade 5.4 0.19 0.33 Turbulent (2.67 × 104 –4 × 104 ) [21]
impellers in flat-bottom
cylindrical vessel with baffles
Rushton turbine and pitched blade 10.8 0.24 0.33–0.50 Transition–turbulent (300–1.5 × 105 ) [23]
impellers in baffled,
flat-bottomed, cylindrical vessel
Blade impellers in baffled vessels 18.5–348 0.287–0.762 0.20–0.32 Transition–turbulentd) (1.4 × 103 –1.59 × 105 ) [11]
Dual-stage Rushton turbine in 20 0.294 0.33 Turbulent (4 × 104 ) [18]
baffled, flat-bottomed,
cylindrical vessel
Rushton turbine, curved and 40 0.40 0.325–0.45 Transition–turbulent (200–2 × 105 ) [12]
pitched blade impellers in a
hemispherical-bottomed
cylindrical, and fully baffled
mixing tank
Two-stage radial disc, pitched 45 0.39 0.41 Turbulentd) (1 × 105 –1.25 × 105 ) [27]
blade, and Lightnin A315
impellers in baffled,
flat-bottomed, cylindrical vessel
a) Relatedto water-like media.
b) Reynolds numbers were calculated from the provided data.
c) The torque sensor was mounted to the bioreactor vessel rather than to the impeller.
d) Reynolds numbers were calculated from the provided data.

available data are for moderate or fully turbulent conditions, but DECHEMA single-use technology working group recommends
there is still a lack of available data for lower Reynolds numbers, estimating power input in single-use bioreactors by determin-
which are relevant for shear sensitive production organisms and ing the impeller torque with torque meters [41, 42], but there
highly viscous, non-Newtonian culture broths. The latter applies, is a lack of experimental data to validate this approach. Hence,
for example, to fungi-based or plant cell based cultures [38–40]. a further aim of the present study is to generate experimen-
Particularly at laboratory scales, most measurement tech- tal data that provides additional evidence for the DECHEMA
niques suffer from a low degree of measurement accuracy. In recommendation. In order to encourage standardization of
temperature-based measurements, this lack of accuracy is related future work, the experimental method is described here in
to low heat generation and losses to the surroundings. However, detail.
in torque-based setups it may be caused by low resolution of the
sensors being used and/or high losses from agitator bearings and
mountings. 2 Materials and methods
Hence, the objective of the present study was to develop
a measurement setup that is suitable for power input mea- 2.1 Tested stirrers and bioreactors
surements in reusable and single-use bioreactors with work-
ing volumes in the one-digit liter range and to determine If not mentioned otherwise, the power input in all bioreac-
power input over a wide range of turbulence conditions. The tors was determined with 2 L working volumes. Initially, the
system was designed to be flexible, easy to use, and repro- power input of a standard Rushton turbine with a diameter d of
ducible, and should offer the possibility for automation. The 53 mm (geometrical details provided in Table 2) was measured

502 
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in order to validate the measurement technique. The turbine

thickness aS /D was mounted into a torospherical bottomed glass vessel (DIN
28011 [43]) with an off-bottom clearance (zM ) equal to d. The
Baffle

0.046
0.046
vessel diameter D was 130 mm and it was fitted with three baf-
(−)

n.a.
n.a.

n.a.
fles (width BS /D = 0.092, length HS /D = 1.17, thickness aS /D
= 0.046) installed through the preconfigured ports in the head
plate of the SmartGlass bioreactor at 120° from each other and
HS /D (−)

with an offset of 3 mm from the vessel wall. In addition, the im-

thickness

pellers used in the SmartGlass 3L bioreactor and the SmartVessel

Baffle

1.17
1.17

n.a.
n.a.

n.a.
3L bioreactor (Finesse Solutions Inc., CA, USA) were also tested.
In this case, the disc blade and segment impellers, both with
diameters of 56 mm, were mounted at a distance of 64 mm from
Baffle width

each other with an off-bottom clearance of 49 mm (zM /d = 0.72).

BS /D (−)

This impeller configuration was tested with and without baffles

0.092
0.092

in the glass tank.

n.a.
n.a.

n.a.

Finally, the power inputs in the UniVessel 2L SU and the Mo-

bius CellReady 3L bioreactors were determined. These bioreac-
thickness s/d

tors are described in detail elsewhere [32].The main geometrical

parameters for all the bioreactors examined in this study are also
Blade

summarized in Table 2.
0.028
0.037
0.024

0.038
0.026
(−)
Blade height

0.20/0.741a)
0.20/0.741a)
b/d (−)

0.181

0.566
0.198

2.2 Measurement setup

Blade angle α

The experimental setup is schematically shown in Fig. 1. The

bioreactor vessels of interest were placed into a vessel holder and
90/45a)
90/45a)

covered by a specially designed stainless steel head plate, which

(°)

25

30
90

required the removal of the original head plates from the single-
use bioreactors. An air bearing with an inner diameter of 13 mm
and length of 50 mm (IBS precision engineering, Netherlands)
distance zR /d

was integrated into the head plate, in order to minimize the load
Impeller

free torque. The porous media bushing, which was supported

1.19
1.19

1.21
(−)

n.a.

n.a.
Table 2. Summary of the geometrical details of the stirrers investigated

with 5.5 bar pressurized air, provided an almost frictionless radial

bearing (see also discussion below).
clearance zM /d

The dynamic torques were measured using a T20WN torque

Off-bottom

meter with a nominal torque of 0.2 Nm (HBM Hottinger Bald-

win Messtechnik GmbH, Germany). The torque meter was held
axially and centrically by a plate that was perpendicularly fixed
0.87
0.87
1.00

0.44

1.02
(−)

to the head plate. According to the manufacturer, the sensor

provides a measurement accuracy and RSD of reproducibility
of ±0.2% and <0.05% of the nominal torque, respectively [44].
diameter d/D

a) Values are given for the lower/upper impellers.

Two metal bellow-type couplings (Uiker AG, Switzerland) were

Impeller

used to install the torque meter between the brushless AC servo

0.43
0.43
0.41

0.55

0.41
(−)

motor (AKM2, Kollmorgen, Germany) and the impeller shaft

with a diameter of 13 mm (tolerance: −0.0076 mm) and length
of 325 mm that was provided by Bioengineering AG (Switzer-
diameter D

land). The bellow-type couplings compensated for parallel and

angular misalignments as well as imbalances of the impeller
(mm)
Vessel

shafts.
130
130
130

130

128

n.a. = not available.

A PC-based RPDPmini control unit (kindly provided by Fi-

nesse Solutions Inc.) was used to control agitation, gas flow, and
SmartVessel 3L
SmartGlass 3L
Configuration

vessel temperature using μTruBio PC control software (v. 3.1).

UniVessel 2L
CellReady
Glass vessel

Rushton
turbine

For data acquisition with Catman easy software (HBM, Ger-

Mobius
with

SU

many), the torque sensor was connected to a Spider-8 AD con-

3L

verter (HBM, Germany).


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Figure 1. Schematic of the ex-

perimental setup. (1) Vessel
holder, (2) air bushing, (3)
torque meter, (4) agitator mo-
tor, (5) heating blanket, (6) con-
troller for motor speed and gas
mass flow, (7) AD converter, and
(8) PC.

2.3 Measurement procedure data. The impeller Reynolds numbers (Re) were then calculated
using Eq. (3):
The power input in the liquid PL was calculated directly from
N · d 2 · ρL
the effective torque (Meff ) and the rotational impeller speed (N) Re = (3)
using Eq. (1): ηL
Using the recipe tool integrated in the μTruBio PC software,
P L = 2 · π · Meff · N = 2 · π · (ML − MD ) · N (1) up to 110 individual measurements could be conducted in a
single experiment. A typical measurement profile is shown in
where Meff was obtained from the difference between the torque Fig. 2, where the impeller speed of the Rushton turbine was in-
measured in liquid ML and the dead torque MD (torque without creased stepwise over time. After each adjustment of the impeller
liquid inside the vessel). The dimensionless power number NP speed, peak values in the torque signal were observed. The peak
(also known as Newton number) was calculated using Eq. (2), torque signal values are related to the PID-based impeller speed
where ρL is the liquid density: controller and the initial acceleration of the liquid. In order to
PL 2 · π · Meff obtain a stable torque signal for each measurement point, the
NP = = (2) impeller speed was kept constant for 3 min and the peak torque
ρL · N 3 · d 5 ρL · N 2 · d 5
after each speed adjustment was ignored. The measured torques
Even though the dead torque is very low, due to the air bear- (ML ) represent the average value obtained from a minimum of
ing, it was determined for each bioreactor for rotational speeds 240 data points with a measurement frequency of 2 Hz, as shown
of between 50 and 900 rpm. However, the effective measure- in Fig. 2. For the majority of measurement points, the RSDs of
ment range was limited to 300 rpm for all unbaffled examples these mean values were lower than 3%, which indicates stable
due to vortex formation, which was limited to vortex depths of measurement signals.
approximately 20 mm based on visual inspection. For each ex-
periment, the vessels were filled with 2 L pure water or sucrose
solution (20–60% w/w). The density and viscosity of the solu- 3 Results and discussion
tions were calculated based on data from [45]. Some reference
measurements were also conducted using a DCAT 11 tensiome- 3.1 Determination of dead torque
ter (Dataphysics, Germany) and a MCR 302 Modular Compact
Rheometer (Anton Paar Switzerland AG). All samples showed Based on our experience, reducing the dead torque (i.e. torque
good agreement (relative deviation 5%) with the literature during agitation without liquid) is one of the most important

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Figure 2. Example measurement in the 2 L

baffled glass bioreactor with a Ruston turbine.
The impeller speed was increased every 3 min
from 150 to 450 rpm in steps of 30 rpm. The
black lines indicate the averaged torque values
of the individual measurement steps.

Figure 3. Dead torque as a function of the im-

peller tip speed in the CellReady 3L bioreactor.
The dashed line indicates the expected effec-
tive torque based on experimental data [32]
and CFD models [46].

factors for accurate power input measurements, particularly in to resolve such small effective torque values, i.e. differences in
laboratory-scale bioreactors, whereas often it does not need to be torque in liquid versus air. This is particularly true for low im-
taken into account in larger vessels, as proposed by [19, 26, 34]. peller speeds.
As can be seen from Fig. 3, the dead torque in the CellReady Using the zero-friction air bearing, the dead torque was ef-
3L bioreactor with the built-in bearing was between 9.4 and fectively reduced to values between 0.4 and 0.9 mN·m. Thus, the
20 mN·m depending on the rotational speed, i.e. tip speed de- ratio Meff /MD (based on the predicted effective torque) was only
fined as: between 0.2 and 1.5. It should be emphasized that the residual
dead torque in the CellReady 3L bioreactor was still the highest
utip = π · N · d (4)
of all the tested bioreactors, which can be explained by the built-
This is up to two orders of magnitude higher than the ex- in impeller shaft fixing on the vessel bottom. During rotation,
pected effective torque based on experimental data [32] and the impeller shaft collided with this fixing, a fact that can also be
computational fluid dynamics (CFD) models [46]. For the Uni- observed during cultivation experiments.
Vessel SU, dead torque values of approximately 3 mN·m at a For the other agitators that were tested, residual dead torque
rotational speed of 150 rpm have been reported [32]. Consider- values in the order of 0.1–0.5 mN·m were observed, which may
ing the measurement accuracy of the sensors used, it is difficult be caused by minor radial misalignments of the impeller shaft.


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Figure 4. Determined power numbers of the Rushton turbine as

a function of the impeller tip speed. The error bars represent Figure 5. Power input of the Rushton turbine as a function of the
the simple SDs of four individual experiments. The dashed lines Reynolds number. Increasing the sucrose mass fraction resulted
indicate the confidence interval based on the sensor accuracy (i.e. in the Reynolds number varying by two orders of magnitude (be-
±0.2% of the nominal torque equal to ±0.4 mN·m). tween 1 × 102 and 3 × 104 ). The solid lines represent regression
models assuming P  Re3 for constant power numbers.

Furthermore, none of the tested agitators had a bearing near the

vessel bottom. Consequently, even very small bends in or imbal- replicates was <5% and the effective torque was 2 mN·m, cor-
ances of the impeller shaft could result in significant oscillations responding to 1% of the nominal torque, were considered in
during rotation, particularly in the single-use bioreactors, due further experiments.
to the fact that their shafts are made out of plastics and are, as a
result, more flexible.

3.3 Power input of standard and single-use agitators

3.2 Measurement reproducibility under nonaerated conditions

Measurement reproducibility was evaluated using a Rushton tur- 3.3.1 Rushton turbine
bine operated at impeller speeds of between 100 rpm and 900 In Fig. 5, the determined power input of the Rushton turbine in
rpm (corresponding to tip speeds of 0.27 and 2.45 m·s−1 ). As a 2 L working volume is shown for Reynolds numbers between
can be seen in Fig. 4, the SDs of the four replicates decrease as 1·102 and 3·104 . Using impeller speeds between 150 and 450
tip speed increases (from 21–<1%). This agreed with expecta- rpm, the Reynolds numbers were also influenced by the liquid
tions due to the lower relative importance of the dead torque and density (998.2–1286.5 kg·m−3 ) and viscosity (0.89–58.5 mPa·s)
the higher absolute torque at elevated impeller speeds. Qualita- of water and the sucrose solutions, with mass fractions of up
tively similar scattering has also been reported after comparisons to 60% w/w. As expected, individual profiles were obtained for
between nine different laboratories (Members of the German each of the liquids, which showed that the power input increased
GVC-VDI working group on mixing) that have measured power as the Reynolds number increased. In the range investigated, it
inputs for Rushton turbines and pitched blade impellers in 0.4 m is well-known that the power number of the Rushton turbine is
diameter vessels, i.e. 50 L scale [47]. Using different measurement almost constant, as reported in several studies [10,12,16]. Hence,
systems, including strain gauges, shaft-mounted torque meters, as can be seen from Eqs. (2) to (3), the power input P follows
and turntables, system intrinsic deviations have been reported the relationship PL  Re3 for a constant impeller diameter. The
for measured values equal to 10% or less of the nominal torque. experimental data agreed well with this correlation (with R2 =
In the present study, the effective torque values obtained with the 0.9992, see Fig. 5).
air bearing were between 0.5 and 16 mN·m, which corresponded The power characteristic of the Rushton turbine is shown
to 0.25 and 8% of the nominal torque of the sensor that was used. in Fig. 6. In agreement with expectations, the power number
Thus, reliable measurements were obtained for very low torque NP decreased at low Reynolds numbers (100 < Re < 500)
values related to the nominal measurement range. before it increased again above Re  2000. Under fully turbulent
It should be emphasized that most measurement points were conditions (Re > 104 ), an almost constant power number of NP
within the confidence interval around the mean values based on = 4.17 ± 0.14 was obtained. These observations showed good
the sensor accuracy provided by the manufacturer (i.e. ±0.2% qualitative agreement with data reported by Shiue and Wong [12]
of the nominal torque equal to ±0.4 mN·m [44]), which is pre- and Ibrahim and Nienow [16] for the Re range investigated (see
sented as a dashed line in Fig. 4. Nevertheless, in order to ensure Fig. 6). These authors have determined the power input of a single
reliable results, only those measurements for which the RSD of Rushton turbine in 20 and 40 L working volumes, respectively.

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However, it should be emphasized that direct comparison

is difficult because of the differences in the geometrical details.
The majority of data that has been published is for flat-bottomed
tanks with four baffles, whereas in the present study, only three
baffles were installed in a vessel with a torospherical bottom.
The number and position of the baffles was given by the pre-
configured ports in the head plate of the SmartGlass bioreactor.
Furthermore, it has been demonstrated that the power num-
ber depends on the diameter ratio (d/D) [10, 49] and the blade
thickness [10, 50], with a relationship of NP  (s/d)−0.22 being
reported [50]. This was confirmed by our own measurements in
a 10 L scale vessel, where NP  (s/d)−0.32 was determined (data
not shown). Finally, it has been stated that the disc thickness also
has a notable influence on the power number [10], but not all
references from Table 3 provide the blade thickness used in their
studies.

3.3.2 SmartGlass bioreactor

Figure 6 also shows the power characteristic of the SmartGlass
Figure 6. The power number as a function of the Reynolds number bioreactor, which is agitated by a combination of a top-mounted
for the stainless steel agitators investigated.
axial flow segment blade impeller (also known as an elephant ear
impeller) and a modified disc blade turbine with tapered blades
However, some discrepancies were found in a more quanti- (i.e. a modified Rushton turbine), where the latter exhibits a pre-
tative comparison. The power numbers for Re < 300 seem to be dominantly radial flow in CFD simulations (data not shown).
overestimated by up to a factor of 2. Although such low Reynolds In the baffled vessel, the total power number continuously de-
numbers are unlikely in animal cell cultures (even at very low creased from NP  6.5 for Re  102 to NP  4.46 for Re > 104 .
impeller speeds) they may be relevant in plant cell cultivations, This indicates that the reduced drag at the disc blade, compared
where increases in the broth viscosity by up to a factor of 400 to a classic Rushton turbine, is equalized by the second impeller.
have been reported [40], resulting in a considerably lower Re In contrast, the power number in the unbaffled SmartGlass
according to Eq. (3). bioreactor decreased over the complete Re range investigated.
Furthermore, the power number for fully turbulent condi- Because this behavior has also been described for various other
tions is up to 25% lower than that provided by reference data unbaffled agitators [1, 49], it agreed with expectations and can
of NP  4.7 [16] and NP  5.5 [12]. As can be seen from be explained by centrifugal forces that result in fluid rotation
Table 3, other researchers found NP values for Rushton turbines and finally the formation of a vortex.
in baffled vessels in a range of 3.6–5.9 [10,14–17,20,27,35,36,48],
depending on the stirrer and vessel geometry used. Furthermore, 3.3.3 SmartVessel bioreactor
an even lower NP value of 3.36 has been reported for an unbaffled Not entirely surprisingly, a very similar power characteristic
Rushton turbine agitated minibioreactor [35]. for the SmartVessel bioreactor (Finesse Solutions, Inc.), the

Table 3. Summary of determined power numbers NP for Rushton turbines under fully turbulent conditions for different geometries reported
in the literature

d/D (−) zM /D (−) s/d (−) t/d (−) a/d (−) b/d (−) Baffles (−) NP (−) Ref.

0.43 0.41 0.027 0.026 0.29 0.20 3 4.17 ± 0.14 This work
0.25–0.75 0.16–0.75 n.a. 0.013–0.11 0.25 0.20 4 3.6–5.9b) [10]
0.31 0.31 0.016 0.024 0.25 0.20 4 4.6 ± 0.4a) [48]
0.33 0.33 0.075 n.a. 0.25 0.20 0 3.36 ± 0.09a) [35]
0.33 0.33 n.a. n.a. 0.25 0.20 4 5.10 ± 0.06a) [20]
0.33 0.33 0.031 n.a. 0.25 0.20 4 5.1a) [15]
0.33 0.25 0.008 n.a. 0.25 0.20 4 5.27 ± 0.05a) [14]
0.41 0.33 0.009–0.076 n.a. 0.25 0.20 4 5.58b) [27]
0.52 0.25 n.a. 0.013 0.25 0.20 4 4.6 ± 0.28a) [17]
0.33 0.20 n.a. n.a. n.a. n.a. 4 5.5b) [36]
0.50 0.25 n.a. 0.05 0.25 0.20 4 5.0b) [16]

In all literature studies, flat-bottomed vessels were examined, whereas the bottom was torospherical in the present work.
a) These data were determined from (logarithmically scaled) graphs in the references given.
b) No information is provided about the relationship between impeller thickness and the power number.

n.a. = not available.


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Figure 7. The power number as a function of the Reynolds number

Figure 8. Power input ratio under aeration in the Mobius Cell-
for the unbaffled single-use bioreactors investigated.
Ready 3L (black symbols) and the SmartGlass 3L (gray symbols)
bioreactors. The gray marked square indicates typical operating
ranges for cell culture applications used in our laboratory.
single-use counterpart of the SmartGlass 3L bioreactor, was also
determined (see Fig. 7). In the unbaffled vessel, a power num-
ber of NP = 2 was determined for Re = 104 . Small deviations it was higher for the two experiments presented in the reference
(with relative values in the range of −25 and +40%, depending study [32], which presumably caused higher experimental er-
on the Reynolds number) between the single-use and multiuse rors. However, the overall agreement between the two studies was
vessel can be explained by differences in the impeller designs. satisfactory.
Even though the shape of the impellers and their main geomet-
ric parameters (d, zM , zR , b, α in Table 2) were identical for both
the stainless steel and the plastic impellers, small modifications
resulting from the manufacturing process could not be avoided. 3.3.5 Mobius CellReady 3L bioreactor
The blades of the plastic impellers were thicker (2 vs. 1.5 mm) Finally, the power input of the Mobius CellReady 3L biore-
and their edges were rounded compared to the sharp-edged steel actor was determined for Reynolds numbers between 2.75 ×
blades. The bottom-mounted shaft holder in the SmartVessel 102 and 3.06 × 104 . Due to the low blade angle of the ma-
bioreactor may also have an impact on the flow structure below rine impeller, the power numbers obtained were only between
the impellers. 0.82 and 0.31. Again comparable experimental values have been
Measurements with lower filling volume, where only the lower reported [32] and were also obtained from numerical CFD
impeller was covered, revealed a power number of 1.3 for Re = models [46].
104 (data not shown). Assuming negligible interactions between
the impellers, something that has been found for systems with
zR /d > 1.2 [49–51], the power number of the upper impeller 3.4 Power input for standard and single-use agitators
would be 0.65. This value is comparable to reported data for a under aerated conditions
similarly shaped elephant ear impeller [51] and also to data from The influence of aeration on the power input was studied for the
the two-stage segment blade impellers in the UniVessel 2L SU single-use Mobius CellReady 3L and the reusable SmartGlass 3L
bioreactor (see discussion below). bioreactors over a wide range of aeration rates (0.125–1 vvm).
In Fig. 8, the ratio of gassed power input to ungassed power
input (PG /PL ) that was obtained from the torque measurements
3.3.4 UniVessel 2L SU bioreactor is shown as a function of the gas flow number Fl, which was
For the UniVessel 2L SU bioreactor, power numbers of between defined as:
5.08 and 1.13 were determined, depending on the Reynolds num- FG
bers (1.5 × 102 < Re < 1.78 × 104 ). These NP values are some- Fl = (5)
N · d3
what lower than experimental data reported by van Eikenhorst
et al. [32], e.g. NP = 1.9 for Re = 1.4 × 104 . Interestingly, where FG is the volumetric gas flow rate. As expected, the
their data showed the same relationship of NP  Re−0.336 as gassed power input in both bioreactors decreased as gas flow
found in the present study for comparable Reynolds number rates increased. At flow numbers of Fl  0.04, the PG /PL ra-
ranges. The different absolute values may be explained by the tio became constant, which has also been reported for tradi-
different measurement techniques. While the dead torque in the tional impellers, such as Rushton turbines [14, 31] and curved
present study was considerably lower than the effective torque, blade impellers [21]. Surprisingly, the Mobius CellReady marine

508 
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impeller showed a higher dependency on the flow rate (PG /PL power characteristic was also determined, which demonstrated
 Fl−0.15 ) than the SmartGlass bioreactor impellers (PG /PL  the suitability of the measurement setup.
Fl−0.04 ), which may be explained by the lower gas dispersion effi- Nevertheless, laminar flow conditions with Re < 100 were still
ciency of the marine impeller. Furthermore, PG /PL ratios slightly not achievable. For such conditions, either a further increase in
above one were determined for low gas flow numbers in the Mo- the liquid viscosity or a decrease in the impeller speed would be
bius CellReady bioreactor, which has also been demonstrated required. Using sucrose solution as a cheap Newtonian model
for hydrofoil impellers [30]. It has been stated that the rising medium, a maximum dynamic viscosity of  60 mPa·s was es-
gas–liquid plume opposes the impeller pumping action at low tablished with mass fractions of 60% w/w, which is close to the
impeller speeds and, therefore, the power numbers under aera- solubility limit at room temperature (66.7% w/w [53]). Alterna-
tion become higher than those under nonaerated conditions at tively, glycerol or silicone oils with viscosities > 1000 mPa·s could
the same speed. be used. The lowest possible impeller speeds were restricted by
Finally, it should be emphasized that the results only the resolution of the torque meter (to 100 rpm in most cases).
consider the measured power input based on the torque, To the best of the author’s knowledge, there are only a few com-
whereas the power input from the gas, which can be calcu- mercially available sensors with lower measurement ranges (e.g.
lated from Eq. (6), assuming isothermal gas expansion, was not with a nominal torque of 0.1 Nm [44]). However, none of these
considered. were used because of the additional investment costs.
This may also limit the use of the current experimental setup
P G,b = F G · (ρL − ρG ) · g · HGL (6)
for smaller bioreactors with volumes of below one liter (and
In fact, the power input released from gas expansion ex- geometrically similar agitators). For instance, a 10% smaller im-
ceeded the measured power input under certain operation con- peller diameter results in an approximately 40% lower impeller
ditions (typically high aeration rates and low impeller speeds). torque for a given impeller speed and shape (i.e. power number),
Nevertheless, it should be noted that aeration rates and gas because of the M  d5 relationship between torque and impeller
flow numbers above 0.25 vvm and 0.015 are typically not used diameter. Consequently, the torque meter and the experimental
for cell culture applications based on protocols developed in set up must be carefully considered. Further work is planned to
our laboratory. Therefore, it can be concluded that the influ- establish an experimental set up for measuring torque in vessels
ence of aeration on power input in the investigated systems is with volumes of 1 L and less.
negligible.

4 Concluding remarks Practical application

Even though the (specific) power input is an important param- Measuring power input in small-scale bioreactors is still
eter for engineering characterization and scaling-up/down of challenging because of the limited accuracy and resolution
bioreactors, only limited experimental data for benchtop scale of common measurement techniques. The torque-based
systems is available in the literature. In particular, little data on methods that currently dominate are often limited by the
power input for laboratory-scale single-use bioreactors, which relatively high friction losses of the bearings that are usu-
come ready to use from the manufacturers, has been published to ally used. Consequently, there is still a lack of data on
date. This study has closed some gaps for commercially available power inputs in benchtop scale bioreactors, in particular
single-use systems at benchtop scale, namely the UniVessel 2L SU, for single-use bioreactors, which are preassembled, steril-
the Mobius CellReady 3L, and the SmartVessel 3L bioreactors. ized, and delivered ready to use from the manufacturers.
The determined power numbers cover a wide range of Reynolds The present study shows that air bearings can be used
numbers between very low and moderate turbulence and are to effectively reduce the friction losses and, thus, enable
regarded as useful for defining suitable operating conditions for accurate measurements for a wide range of operational
most cell culture applications (or even microbial processes with conditions. Based on reference measurements with a con-
moderate agitation requirements). Finally, this study has also ventional Rushton turbine, which agreed well with literature
demonstrated that the power input in the bioreactors investi- data, the power inputs in different multiuse and single-use
gated is only slightly influenced by typical cell culture aeration bioreactors were determined for low-to-moderate turbu-
rates. lence, which is often found in cell culture based processes
Based on the current results, it can be concluded that the with low agitation.
recommendations provided by the DECHEMA working group
guidelines [42] are also applicable for bioreactors at the benchtop
scale. During the development of the test setup, special attention
was given to reducing the dead torque that usually limits the mea-
surement range and accuracy, particularly for small agitators. By The authors would like to thank Dieter Häussler and Beat Gautschi
using an air bearing, as has already been described in previous for their assistance during the experimental set up. We are also
works [10, 52], it was possible to minimize the dead torque to grateful to Darren Mace for English proof reading.
values of below 1 mN·m, irrespective of the impeller speed and
bioreactor used. Good agreement was found with available lit-
erature data for the standard Rushton turbine used. The typical The authors have declared no conflicts of interest.


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