Bioreactor Scale-Up: P/V, Tip Speed and Mixing Time

Calculate bioreactor scale-up at constant P/V, tip speed, mixing time or estimated kLa. Compare speed, power and trade-offs with animated tank views.

#bioreactor #kLa #mixing time #power per volume #Rushton turbine #scale-up #tip speed

This bioreactor scale up calculation helps process engineers, students and laboratory teams compare operating speeds before moving a stirred process to a larger vessel. Choose the quantity to preserve: power per working volume, impeller tip speed, 95% mixing time or estimated volumetric oxygen-transfer coefficient, kLa. The calculator finds the large-scale speed and shows what happens to the other quantities.

Enter the two working volumes, the small impeller’s outer diameter and its speed. Supply the liquid density, dynamic viscosity and an ungassed impeller power number appropriate to the actual geometry. The default power number, 5.47, is a published Rushton-turbine measurement; it is an example rather than a universal value. The tanks are assumed to be geometrically similar, baffled cylinders with one impeller and liquid height equal to tank diameter. The large impeller diameter follows from the cube root of the volume ratio.

For constant P/V scale up, the larger impeller turns more slowly, but its tips travel faster and the blend time becomes longer. Using this as an impeller tip speed calculator instead holds the peripheral velocity constant and generally reduces power per volume. Constant mixing time requires the same rotational frequency under the assumed geometry, so both power density and tip speed increase with size. The comparison table puts these alternatives beside the small reference vessel.

Aeration needs its own decision. Keeping gas volume per liquid volume per minute, usually called vvm, makes superficial gas velocity rise with tank size. Keeping superficial gas velocity constant makes vvm fall. The kLa option uses the coalescent-water van’t Riet correlation and an assumed gassed-to-ungassed power fraction. It preserves a model estimate, not a measured culture response. At constant superficial gas velocity, its required speed coincides with constant P/V because liquid properties and the power fraction are held equal.

Press play to compare the impellers at their calculated rotation rates. The top views use separate drawing scales so both impellers remain visible; the motion uses real seconds. At high speeds, screen sampling can make the blades appear to rotate slowly or backwards.

Use the results for preliminary comparison and to plan measurements. The mixing-time correlation describes turbulent, single-phase blending to 95% homogeneity; it is not a validated aerated-broth mixing model. The kLa estimate applies to nonviscous coalescent liquids and needs experimental confirmation for media containing salts, surfactants or antifoam. The tool does not predict flooding, shear damage, oxygen demand, dissolved-oxygen concentration, carbon-dioxide removal, heat transfer, shaft strength or motor rating. Tall vessels, multiple impellers and non-Newtonian broths require other models.

How it is calculated

The geometry is a cylindrical working volume with H = T, one centrally mounted impeller, and four baffles. Let NN be revolutions per second, DD impeller diameter and TT tank diameter. The length scale factor is λ=(V2/V1)1/3\lambda=(V_2/V_1)^{1/3} and D2=λD1D_2=\lambda D_1. Density, viscosity, impeller geometry and power number stay equal.

Power and kinematics follow P=NpρN3D5P=N_p\rho N^3D^5, utip=πNDu_{\rm tip}=\pi ND and Re=ρND2/μRe=\rho ND^2/\mu. Power is the ungassed shaft power delivered to the liquid, excluding motor and transmission losses. The default Np=5.47N_p=5.47 is the measured Rushton example in Loo et al. (2019), attached PDF page 5, Power Number results; replace it with a value for the actual impeller.

For turbulent single-phase blending, the Grenville–Nienow correlation at H/T = 1 is

t95N=5.2Np−1/3(T/D)2.t_{95}N=5.2N_p^{-1/3}(T/D)^2.

Rodgers et al. (2011), Eq. 1, reproduces the general correlation and explains its aspect-ratio limit. Here this reduces to the same dimensionless blend time at both scales.

Aeration is specified at vessel conditions. Qg=βVQ_g=\beta V, ug=Qg/(πT2/4)u_g=Q_g/(\pi T^2/4) and Pg=fgPP_g=f_gP. For constant vvm, ug,2/ug,1=λu_{g,2}/u_{g,1}=\lambda; for constant superficial gas velocity this ratio is one.

Estimated kLa uses van’t Riet’s coalescent, nonviscous-liquid model, reproduced in DECHEMA (2020), attached PDF page 17, Eqs. 7–11:

kLa=0.026(Pg/V)0.4ug0.5.k_La=0.026(P_g/V)^{0.4}u_g^{0.5}.

Use P_g/V in W/m³ and u_g in m/s to obtain kLa in s⁻¹, then convert to h⁻¹. The normalized calculation steps preserve these empirical SI conventions.

Required speed ratios are λ−2/3\lambda^{-2/3} for constant P/V, λ−1\lambda^{-1} for constant tip speed, and 1 for constant mixing time. For constant estimated kLa the speed ratio is λ−2/3(ug,2/ug,1)−0.5/(3×0.4)\lambda^{-2/3}(u_{g,2}/u_{g,1})^{-0.5/(3\times0.4)}.

What each choice changes: Constant P/V increases tip speed and lengthens mixing time. Constant tip speed reduces P/V and lengthens mixing time; kLa can rise or fall depending on the gas rule. Constant mixing time raises P/V as λ2\lambda^2 and tip speed as λ\lambda. Constant estimated kLa changes power density, mixing time and tip speed according to the aeration rule. The table gives the numerical trade-offs for the current inputs.

Assumptions

  • Geometrically similar baffled tanks, cylindrical liquid volume, H/T = 1, one impeller, and unchanged relative clearance and baffle dimensions.
  • Incompressible Newtonian liquid; density, viscosity and the turbulent ungassed power number remain unchanged.
  • The entered gassed/ungassed power fraction is an assumption applied equally at both scales. The default 0.7 is an illustrative estimate, not a measured value for the default tank.
  • kLa uses coalescent, water-like gas–liquid behavior with the same liquid composition, gas, sparger characteristics and pressure regime. Salts, antifoam and surfactants can invalidate that estimate.
  • The equations for geometric scaling and the four speed ratios are derived here from the cited power, kinematic, mixing and mass-transfer relationships.
  • The animation is a schematic top view of a six-blade impeller at each tank’s own drawing scale. Angular motion uses physical seconds and calculated rpm. It does not simulate the liquid flow.

Where it applies

Use for preliminary scale-up comparison, with Re ≥ 10,000 and approximately 0.25 ≤ D/T ≤ 0.50. The Reynolds warning considers every row of the comparison table, including criteria that are not currently selected. The 5 mPa·s viscosity reminder is a conservative screening flag for the nonviscous kLa model, not a published sharp boundary.

DECHEMA reports application of the cited van’t Riet models in conventional sparged stirred vessels from 50 L to 4 m³ (PDF page 17). Outside this range, the scale-up equations remain useful but absolute kLa is an extrapolation. No accuracy guarantee is implied within that range either: confirm mixing time, gassed power and kLa experimentally.

The 95% blend time is a turbulent single-phase bulk-mixing estimate. Gas loading, feeding location, zoning, non-Newtonian rheology, solids, multiple impellers and tall tanks require validated extensions. Tip speed is a comparative kinematic quantity, not a universal cell-damage threshold; Nienow (2006) discusses why hydrodynamic and biological constraints must be assessed together.

Neither matching kLa nor P/V establishes oxygen sufficiency or equivalent cell growth. Oxygen demand, saturation concentration, CO₂ stripping, flooding, foam, heat transfer, motor sizing and mechanical design are outside the model. Gas flows must be evaluated at vessel conditions; standard volumetric flow needs pressure and temperature correction.

References

  • Nienow, A. W. (2006). Reactor engineering in large scale animal cell culture. Cytotechnology 50, 9–33. https://doi.org/10.1007/s10616-006-9005-8
  • Rodgers, T. L. et al. (2011). Mixing times for process vessels with aspect ratios greater than one. Chemical Engineering Science 66, 2935–2944, Eq. 1 (Grenville–Nienow correlation). https://doi.org/10.1016/j.ces.2011.03.036
  • Loo, H. et al. (2019). Effect of disc-blade intercepting angle on mixing performance in a multiphase stirred vessel. Brazilian Journal of Chemical Engineering 36(2). Measured Rushton Np = 5.47. https://doi.org/10.1590/0104-6632.20190362s20180268
  • DECHEMA Expert Group Single-Use Technology (2020). Recommendations for process engineering characterisation of single-use bioreactors and mixing systems by using experimental methods, 2nd edition. Attached PDF page 17, Eqs. 7–12. https://dechema.de/dechema_media/Downloads/Positionspapiere/Single_Use_BioReactors_2020-p-20006899.pdf
  • van’t Riet, K. (1979). Review of measuring methods and results in nonviscous gas-liquid mass transfer in stirred vessels. Industrial & Engineering Chemistry Process Design and Development 18, 357–364. https://doi.org/10.1021/i260071a001
  • Li, B., Becken, U. and Sha, M. (2016). Tackling the Challenge of Scalability: Fermentation Systems for Bioprocess Scale-up from Small to Pilot/Production. Figure 2A tip-speed reference values. https://www.eppendorf.com/media/MAIN/OT-Others/TypoAssets/Publication_DASGIP-Parallel-Bioreactor-System_BioFlo-320_610_Pro_Tackling-the-challen-1.pdf
  • Fluids documentation, agitator_time_homogeneous, published first numerical example and source code, accessed 28 October 2026. The reference-case description documents the extraneous gravity factor in that implementation. https://fluids.readthedocs.io/fluids.mixing.html#fluids.mixing.agitator_time_homogeneous

Inputs

InputSymbolUnitDefault
Keep constant
Compare all four choices in the results table. P/V and mixing time use ungassed power; kLa uses estimated gassed power.
criterionPower per volume (P/V)
Small working volume
Cylindrical liquid volume, with liquid height equal to tank diameter. One impeller and four baffles.
V_1L50
Large working volume
All lengths, including the impeller, scale with the cube root of the volume ratio.
V_2L1000
Small impeller diameter
Use the outer diameter. The recommended impeller-to-tank diameter ratio is 0.25–0.50.
D_1m0.16
Small impeller speedn_1rpm200
Ungassed power number
5.47 is a published six-blade Rushton value (Loo et al., 2019, attached PDF page 5). Use a measured number for your exact impeller; it is held equal at both scales.
N_p5.47
Liquid density
Range: 500–2,000 kg/m³ (31.2–124.9 lb/ft³). You can enter or select another density unit.
rhokg/m^31000
Dynamic viscosity
Newtonian, water-like liquid. Reynolds numbers below 10,000 are outside this turbulent model.
mumPa*s1
Gas scale-up rule
At constant vvm, superficial gas velocity rises with tank diameter. At constant superficial velocity, large-scale vvm falls.
gas_ruleKeep volumetric aeration rate (vvm)
Small volumetric aeration rate (vvm)
Gas volume per liquid volume per minute, evaluated at vessel conditions. Do not enter a standard flow without correcting its pressure and temperature.
beta_11/min0.1
Gassed / ungassed power fraction
Screening assumption, held equal at both scales. Replace with a measured fraction. It is not a flooding or gas-dispersion model.
f_g0.7
Rotation time ▶
The impellers turn at the calculated physical speeds, in real time. The six blades can appear to alias at high speeds.
t_anims0.17

Results

With the default inputs above, the calc gives:

ResultValue
Large impeller speed102.78 1/min
Large ungassed power to liquid424.867 W
Large ungassed P/V424.867 W/m³
Large tip speed2.337 m/s
Large impeller Reynolds number323,113
Large estimated 95% mixing time10.73 s
Large estimated kLa38.82 1/h

Checked against sources

Each case below was calculated by this calc and agrees with the value from its source (within the tolerance where one is shown).

Eppendorf DASGIP tip speed: 498 rpm gives 1.2 m/s

Source: Li, Becken and Sha (2016), Figure 2A: DASGIP 498 rpm at tip speed 1.2 m/s; 46 mm impeller (Eppendorf Rushton product 78100557). https://doi.org/10.1089/gen.36.09.14 . Checks tip kinematics only; the H=T equivalent tank is not a reconstruction of this multi-impeller fermenter.

Inputs: Small working volume = 1 L; Large working volume = 1 L; Small impeller diameter = 0.046 m; Small impeller speed = 498 rpm; the others as above.

ResultSourceThis calc
Small impeller tip speed1.2 m/s1.199 m/s

Eppendorf DASGIP tip speed: 1163 rpm gives 2.8 m/s

Source: Li, Becken and Sha (2016), Figure 2A: DASGIP 1163 rpm at tip speed 2.8 m/s, impeller OD 46 mm. https://doi.org/10.1089/gen.36.09.14 . The published speed is rounded to whole rpm. Only tip speed is checked, not measured mixing time or gas transfer.

Inputs: Small working volume = 1 L; Large working volume = 1 L; Small impeller diameter = 0.046 m; Small impeller speed = 1,163 rpm; the others as above.

ResultSourceThis calc
Small impeller tip speed2.8 m/s2.801 m/s

Published 1.83 m tank: dimensionally corrected mixing-time benchmark

Source: Fluids agitator_time_homogeneous first published example: T=H=1.83 m, D=36 inches, N=56 rpm, P=957 W, rho=1020 kg/m³, mu=0.018 Pa·s; documented t99.5=15.143198226374668 s. https://fluids.readthedocs.io/_modules/fluids/mixing.html . The source code uses Np=P*g/(rho*N³*D⁵), adding g despite specifying watts. This is dimensionally inconsistent with SI Np=P/(rho*N³*D⁵). We retain correct physics. The independent published time, corrected by g^(1/3) and converted from 99.5% to 95% by ln(0.05)/ln(0.005), is 18.3269218795 s. Input Np=1.8051793183 is recovered from the published 957 W; only mixing time is tested. The source's 18 mPa·s liquid is used for this single-phase turbulent benchmark; no kLa claim is made. The attached citation is the SI power-number definition in Loo et al. (2019), PDF page 4, Eq. 3; it supports removing the gravity factor. The time benchmark itself is the explicitly corrected Fluids example linked above.

Inputs: Small working volume = 4,813 L; Large working volume = 4,813 L; Small impeller diameter = 0.9144 m; Small impeller speed = 56 rpm; Ungassed power number = 1.805; Liquid density = 1,020 kg/m³; Dynamic viscosity = 18 mPa·s; the others as above.

ResultSourceThis calc
Small estimated 95% mixing time18.327 s18.327 s

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