1. Heat Transfer in Fermentation

2. 2 Several important chemical engineering concepts in Bioprocess Engineering are transport phenomena (fluid flow, mixing, heat and mass transfer), unit operations, reaction engineering, and bioreactor engineering. Fluid flow, mixing, and reactor engineering are skipped in this class. They are available more detail in several chemical engineering books. We start with the heat transfer in bioreactors

3. In situ batch sterilization of liquid medium. In this process, the fermenter vessel containing medium is heated using steam and held at the sterilization temperature for a period of time; cooling water is then used to bring the temperature back to normal operating conditions Temperature control during reactor operation. Metabolic activity of cells generates heat. Some microorganisms need extreme temperature conditions (e.g. psycrophilic, thermophilic microorganisms) Heat transfer configurations for bioreactors: jacketed vessel, external coil, internal helical coil, internal baffle-type coil, and external heat exchanger. 3

4. External jacket and coil give low heat transfer area. Thus, they are rarely used for industrial scale. Internal coils are frequently used in production vessel; the coils can be operated with liquid velocity and give relatively large heat transfer area. But the coil interfere with the mixing in the vessel and make cleaning of the reactor difficult. Another problem is film growth of cells on the heat transfer surface. External heat exchanger unit is independent of the reactor, easy to scale up, and provide best heat transfer capability. However, conditions of sterility must be met, the cells must be able to withstand the shear forces imposed during pumping, and in aerobic fermentation, the residence time in the heat exchanger must be small enough to ensure the medium does not become depleted of oxygen. 4

5. Double-pipe heat exchanger Shell and tube heat exchanger Plate heat exchanger Spiral heat exchanger In bioprocess, the temperature difference is relatively small. Thus, plate heat exchanger is almost never being used The concepts and calculation for heat exchangers and their configurations are available in the text book ( Pauline Doran, Bioprocess Eng Principle, chapter 8) 5

6. Mass Transfer in Fermentation

7. dy dC DJ A ABA = 7 The Ficks law of diffusion Role of diffusion in Bioprocess Scale of mixing Mixing on a molecular scale relies on diffusion as the final step in mixing process because of the smallest eddy size Solid-phase reaction The only mechanism for intra particle mass transfer is molecular diffusion Mass transfer across a phase boundary Oxygen transfer to gas bubble to fermentation broth, penicillin recovery from aqueous to organic liquid, glucose transfer liquid medium into mould pellets are typical example.

8. 8 The two film theory is a useful model for mass transfer between phase. Mass transfer of solute from one phase to another involves transport from bulk of one phase to the interface, and then from the interface to the bulk of the second phase. This theory is based on idea that a fluid film or mass transfer boundary layer forms whenever there is contact between two phases. According to film theory, mass transfer through the film is solely by molecular diffusion and is the major resistance. CA1i CA1 Bulk fluid 1 Bulk fluid 2 CA2i CA2 Film 2 Film 1

9. ( ) ( )AGiAGGAG ALALiLAL CCakN CCakN = = ( )AiAoA CCkaN = 9 It refers to mass transfer occurring in the presence of bulk fluid motion k: mass transfer coefficient [m/s] a: area available for mass transfer [m2 /m3 ] CAo: concentration of A at bulk fluid CAi: concentration of A at interface For gas-liquid system, A from gas to liquid:

10. ( )ALALLA LGG CCaKN ak m akaK = += * '11 10 Refers to the book Geankoplis (2003), Transport Processes and Separation Process Principles, 4th ed, chapter 10.4. Oxygen transport to fermentation broth can be modeled as diffusion of A through stagnant or non-diffusing B. If A is poorly soluble in the liquid, e.g. oxygen in aqueous solution, the liquid-phase mass transfer resistance dominates and kGa is much larger than kLa. Hence, KLa kLa.

11. Eight steps involved: i. Transfer from the interior of the bubble to the gas-liquid interface ii. Movement across the gas-liquid interface iii. Diffusion through the relatively stagnant liquid film surrounding the bubble iv. Transport through the bulk liquid v. Diffusion through the relatively stagnant liquid film surrounding the cells vi. Movement across the liquid-cell interface vii. If the cells are in floc, clump or solid particle, diffusion through the solid of the individual cell viii. Transport through the cytoplasm to the site of reaction. 11

12. i. Transfer through the bulk phase in the bubble is relatively fast ii. The gas-liquid interface itself contributes negligible resistance iii. The liquid film around the bubble is a major resistance to oxygen transfer iv. In a well mixed fermenter, concentration gradients in the bulk liquid are minimized and mass transfer resistance in this region is small, except for viscous liquid. v. The size of single cell