FLUID FLOW AND MIXING IN BIOREACTORS (Part 2 of 2)

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1 FLUID FLOW AND MIXING IN BIOREACTORS (Part 2 of 2)

2 Overview Power requirements for mixing Newtonian and non-newtonian liquids Ungassed and gassed systems Scale-up issues, scale-down approach Adapting bioreactor design to enhance mixing Effect of fluid rheology on mixing Shear in stirred bioreactors Shear damage to cells in bioprocesses

3 Mixing power (ungassed Newtonian fluids) depends on impeller geometry, size and rotation speed Fluid density and viscosity Power relationships expressed in terms of Dimensionless Power No. (N p ): p ρ P = power; ρ = liquid density; D i = impeller diameter; N i = rotation speed N = P N D 3 i 5 i

4 Mixing power (ungassed Newtonian fluids) 1! Rushton turbine; 2! Paddle; 3! Marine propeller

5 Mixing power (ungassed Newtonian fluids)

6 Mixing power (ungassed Newtonian fluids) 1! Anchor impeller 2! Helical ribbon impeller

7 Mixing power (ungassed Newtonian fluids)

8 Mixing power (ungassed Newtonian fluids) Power requirement is calculated from: 3 5 P = N p ρ Ni Di 1 For Re i in the laminar range, N p Re 2 3 i or, P = k µ N 1 i Di For fully turbulent conditions, N p is constant ' N p = N p In the transition region, N p is obtained from the graph

9 Mixing power (ungassed non-newtonian fluids)

10 Mixing power (ungassed non-newtonian fluids) For Re i < 10 and Re i > 100, N p is the same as for Newtonian fluids For 10 < Re i < 100, power absorption less than in Newtonian fluids Apparent viscosity values to be used in Reynold s No. calculation Difficulties in estimating power due to variation in viscosity with position in the fermenter with fermentation time

11 Effect of gas sparging on mixing power Power consumption less with gas sparging due to reduced average liquid density gas cavities behind stirrer blades (less fluid resistance)

12 Effect of gas sparging on mixing power An approximate expression for reduced power requirement is P P g 0 Fg = 0.1 NiV Ni D gwiv 4 i 0.20 P g = gassed power; P 0 = ungassed power F g = volumetric gas flow rate; W i = impeller blade width V = liquid volume The reduction in power absorption not uniform because gas cavity formation is random 2 3

13 Scale-up : Scale-up of mixing development of production scale bioreactor design specifications based on operating data from laboratory or pilot scale equipment aims to achieve conditions at production scale close to the optima determined at pilot scale (e.g. mixing time) In larger vessels liquid to circulate over longer distances (in proportion to vessel diameter or height) fluid velocity must be greater for constant mixing time

14 Fluid velocity: Scale-up issues v Increasing fluid velocity requires increased power input per unit volume of liquid Required increase in power to maintain constant t m is often technically and economically not feasible For scale-up based on constant (P/V), P V t 2 3 m D t mixing time increases with vessel size process performance may be adversely impacted

15 Scale-down approach to process development If the desired conditions cannot be attained at production scale, scale-down approach may help identify best achievable performance of the process Involves pilot-scale process development under conditions realistically achievable at full-scale e.g. investigations under reduced power input to simulate mixing time achievable at full scale.

16 Adapting reactor design to enhance mixing Positioning of impeller at 1/3 vessel diameter from base in standard single impeller vessels promotes asynchronous circulation loops Use of multiple impellers in tall vessels (H L >>D t ) optimum impeller spacing is 1 to 1.5 times impeller diameter closer spacing interferes with circulation loops development and increases power consumption fluid exchange between the different mixing cells inadequate at larger spacing power absorption proportional to the No. of impellers multiple substrate feed points for more even distribution

17 Adapting reactor design to enhance mixing With pseudoplastic fluids, stagnant zones can develop away from the impellers Larger impeller will improve the extent of the agitated region, although power consumption may become too large Special, low clearance impeller designs (e.g. anchor or helical ribbon) can also improve the extent of mixing as they sweep the entire liquid volume

18 Shear in stirred bioreactors Average shear in stirred bioreactors: Increasing shear rate = kn i responsible for dispersing gas bubbles will improve oxygen mass transfer may also lead to cell damage, especially in plant and animal cell culture Shear varies greatly with location in the vessel high in the impeller zone low, away from the impeller where turbulence is low γ&

19 Shear damage to cells in bioreactors In ungassed systems, liquid shear in turbulent eddies is the main cause of cell damage and disruption to cell function In gassed systems, bursting of bubbles at the liquid surface appear to be the principal cause of damage to cells

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