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23-Chem-B4 Biochemical Engineering · May 2014

Question 1 of 6: Bioreactor Scale-Up Criteria

Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)

Notes on this paper

National Exam 04-Chem-B4, Biochemical Engineering — May 2014. 3 hours, Closed-Book Exam (any non-communicating calculator permitted). Six questions are printed; per the exam notes any five (5) constitute a complete paper (100 marks) and only the first five as they appear in the answer book are marked. All six are solved below for completeness.

Reference texts: Shuler & Kargi, Bioprocess Engineering: Basic Concepts, 2nd ed.; Bailey & Ollis, Biochemical Engineering Fundamentals, 2nd ed.; Madigan et al., Brock Biology of Microorganisms, 13th ed.

Question 1: Bioreactor Scale-Up Criteria (20 marks)

Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.

Given.

QuantitySymbolSmall (lab) vessel
Tank diameterDt112 in
Liquid heightH150 cm
Impeller diameter (pitched-blade turbine)Di14 in
Impeller speedN160 rpm
Volume ratio (large : small)V2/V1100

Find. The large-vessel impeller speed N2 for each of four scale-up criteria: (a) equal Re, (b) equal P/V, (c) equal pumping rate, (d) equal tip speed.

Approach. Geometric similarity means every linear dimension — tank diameter, liquid height, impeller diameter — scales by the same factor R, fixed by the volume ratio (V ∝ L³). Each scale-up rule then reduces to a power-law relation between N and Di whose exponent comes from how Reynolds number, power, pumping (flow) number, and tip speed depend on N and Di for a stirred-tank impeller.

small (lab) vesselDₜ₁ = 12 in, H₁ = 50 cmDᵢ₁ = 4 in, N₁ = 60 rpmlarge (production) vesselV₂ = 100 V₁ ⇒ geometrically similarDᵢ₂ = Dᵢ₁·R, Dₜ₂ = Dₜ₁·R, R = 100^(1/3) = 4.642Fig. 1 — geometric similarity: every linear dimension scales by R = (V₂/V₁)^(1/3)
Fig. 1 — geometric similarity: every linear dimension scales by R = (V2/V1)1/3.
  1. Linear scale factor from the volume ratio. For geometrically similar vessels every length scales by the same ratio R, so volume (which scales as length cubed) fixes R directly: $$R=\frac{D_{i2}}{D_{i1}}=\frac{D_{t2}}{D_{t1}}=\left(\frac{V_2}{V_1}\right)^{1/3}=100^{1/3}=\boxed{4.642}$$
  2. (a) Equal impeller Reynolds number. $Re=\rho N D_i^2/\mu$ is held constant between scales (same fluid, so ρ, μ cancel), giving $N_1D_{i1}^2=N_2D_{i2}^2$: $$N_2=N_1\left(\frac{D_{i1}}{D_{i2}}\right)^2=N_1R^{-2}=60\times(4.642)^{-2}=\boxed{2.79\ \text{rpm}}$$ Matching Reynolds number forces the impeller speed to drop sharply with scale, since the larger impeller diameter alone already increases Re by R².
  3. (b) Equal power per unit volume. In the fully turbulent regime the power number $N_P=P/(\rho N^3D_i^5)$ is constant, so $P\propto \rho N^3D_i^5$; dividing by volume ($V\propto D_i^3$ at fixed geometry) gives $P/V\propto N^3D_i^2$. Holding this constant between scales: $$N_1^3D_{i1}^2=N_2^3D_{i2}^2\ \Rightarrow\ N_2=N_1\left(\frac{D_{i1}}{D_{i2}}\right)^{2/3}=N_1R^{-2/3} =60\times(4.642)^{-2/3}=\boxed{21.6\ \text{rpm}}$$ This is the criterion most often used for shear-sensitive but mass-transfer-dependent cultures, since P/V tracks the volumetric mixing/mass-transfer intensity (kLa).
  4. (c) Equal impeller pumping (circulation) rate. The flow number $N_{Fl}=Q/(ND_i^3)$ is constant, so the volumetric pumping rate $Q\propto ND_i^3$. Equal Q between scales gives $N_1D_{i1}^3=N_2D_{i2}^3$: $$N_2=N_1\left(\frac{D_{i1}}{D_{i2}}\right)^3=N_1R^{-3}=60\times(4.642)^{-3}=60/100=\boxed{0.600\ \text{rpm}}$$ (Consistent with the volume ratio itself: $D_{i2}^3/D_{i1}^3=R^3=100$, the same 100× that defined the scale-up.)
  5. (d) Equal impeller tip speed. Tip speed $v_{tip}=\pi ND_i$ constant gives $N_1D_{i1}=N_2D_{i2}$: $$N_2=N_1\left(\frac{D_{i1}}{D_{i2}}\right)=N_1R^{-1}=60/4.642=\boxed{12.9\ \text{rpm}}$$ Tip-speed matching is the criterion typically chosen to protect shear-sensitive cells (mammalian/plant cultures), since maximum shear near the blade tip scales directly with $v_{tip}$.
Scale-up criterionN₂ (rpm)
Linear scale factor R4.642
(a) Equal impeller Reynolds number2.79
(b) Equal power per unit volume (P/V)21.6
(c) Equal impeller pumping rate0.600
(d) Equal impeller tip speed12.9
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