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Reactor Design II

This article explores the intricacies of metabolic heat production during cell growth in bioreactors, highlighting the challenges faced in large-scale reactor designs. It details the relationship between heat production rates and cell growth or oxygen consumption, emphasizing the importance of effective heat removal strategies as reactor size increases. The piece discusses various solutions for managing heat, including increasing heat transfer area, modifying cooling fluids, and controlling growth rates. Each method's implications for reactor efficiency and cell health are considered, providing a comprehensive guide for optimizing bioprocesses.

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Reactor Design II

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  1. Reactor Design II Heat transfer

  2. Metabolic Heat Production • When cells grow they also produce a heat of reaction of about 2.3 kcal/gram of cells produced.

  3. Heat Production Rate • The heat production rate can be related to the rate of cell growth or the O2 consumption rate (OUR).

  4. Scale-up Problem • Removing the heat from the reactor becomes more difficult the larger the reactor. 10 x

  5. Production and Removal Rates • Heat is produced at the same rate per liter regardless of scale • Heat is removed according to the available surface area.

  6. Small vs Large Reactor Design Issue

  7. Surface Area vs Volume • For jacketed reactors, the surface area per liter of reactor drops at a rate proportional to V-1/3 SA = K/V1/3 At large volumes (over 1000 L) this leads to difficulties removing the metabolic heat.

  8. Heat Management • There are 3 reasonable options for managing the heat. • Increase the heat transfer area Rate of heat removal = UA(Treactor – Tjacket) • Increase the temperature difference (by lowering Tjacket) • Reduce the heat production rate by growing the cells more slowly (reduce m)

  9. Jacket Heat Transfer Coefficient • A reasonable overall heat transfer coefficient between the jacket and tank is: U = 100 BTU/ft2-F-hr

  10. Jacket Area • The area for heat transfer in reactors is dictated by the area of the jacket. Jacket area

  11. Cooling Coils • To add more heat transfer surface area to a given reactor size, cooling coils are added. Cooling coils

  12. Cooling Coils • Cooling coils have some negatives • The job of cleaning the reactor and proving it is clean is much harder • The coils may create dead zones to getting oxygen to the cells • The coil material usually cannot be copper so conductive heat transfer may be an issue.

  13. Cooling Liquid • The cooling solution temperature is limited • Tap water minimum is about 10 C. • Glycol chilling loops can go down to -20 C, but are expensive to operate. Cross contamination must be avoided.

  14. Growth Rate vs Heat Production • The heat production rate is lowered by lowering the specific growth rate Rate of heat production (per unit volume)= mXDH Heat production per gram cells is fairly constant m drops 50% for each 8 -10 C temperature drop Cell mass per unit volume

  15. Growth Rate • Mammalian cells grow slowly and rarely have heat production issues • It may be better to grow bacterial cells at lower temperature to prevent protein misfolding.

  16. Summary • In large reactors, metabolic heat management becomes as or more important than O2 transfer. Consideration must be made of: • Adding heat transfer area • Changing cooling fluid • Growing cells at a slower rate

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