Figure 6. Piping and Instrumentation Drawing of the cooling section of a continuous sterilizer.

4.3 The Sterilizing Section

The hot section (Fig. 5) is controlled by a cascade loop which is based on a selected pumping rate (150 gpm) and sterilization temperature set in the TIC. Changes in the feed temperature are monitored at TT1 which will automatically override the steam supply to keep the temperature at set point. Steam flow rate is monitored (by FE) and flow is automatically compensated should a large draw down of steam occur elsewhere in the plant. Temperature is recorded at the beginning and end of the hot section. The hot section should be well insulated and special care should be given to the pipe supports for expansion. (Instrumentation symbols used here and in Figs. 3, 5, 6 and 7, conform to the standard symbols of the Instrument Society of America.)

The pumping rate, the pipe diameter and the length of the hot section of the sterilizer, fix an average retention time. The design basis of the retention time depends upon the bacterial spore count, the maximum particle size of the suspended solids, and the fluid velocity. For economy, the minimum velocity which gives turbulent flow should be used, i.e., aReynold's number of about 3 000 to keep the pipe short and the pressure drop low. The installation of (carefully selected) short static mixers can help in some cases to increase turbulence, reduce the velocity and the length of the hot section. Due to the source of raw materials normally used in fermentation media, bacterial counts can run very high, and some suspended solids can be almost hydrophobic. Based on the particle size which will pass through the screen stated above, three minutes retention time is borderline for sterilization. Five to six minutes retention time is often designed because, in time, inorganic scale will deposit on the wall of the hot section resulting in a smaller diameter and a higher fluid velocity or a shorter retention time. The hot section is easily cleaned once a year to remove the scale.

4.4 The Cooling Section

Most commercial fermentation processes use media with a high concentration of dissolved and suspended solids. Unless a uniform flow profile is maintained, solids may build up in the cooling section. The following are examples of types of heat exchangers to be considered for continuous sterilizers of fermentation media.

Concentric Double Pipe Heat Exchangers. This type of heat exchanger offers the most advantages for a continuous sterilizer with a range of flow rates suitable to the vast majority of commercial fermenters. (Wiseman states production fermenters are 25-1000 m3.[5])

- It is not limited by the flow ratio of the media and the cooling water

- It has the least crevices for corrosion.

- It requires the least cleaning and is cleaned relatively easily

- Scale in the cooling section is relatively minor.

- The velocity profile and pressure drop do not result in heat transfer difficulties

- It is easy to operate and instrument

The cooling section, Fig. 6, is of double pipe construction. Cooling water and sterile media pass countercurrently. The back pressure control valve (for sterilization) is located at the low point of the piping. A Masoneilon Camflex™ valve is a suitable design for this service. A steam bleed should be located on each side of this valve in order to sterilize the sterilizer forward from the steam injector and backward from the fermenter.

Notice also, there is no liquid metering device on the sterilizer. From a maintenance standpoint, it is much preferred to have dP cells on the fermenters for filling and controlling the volume than to measure the volume pumped through the sterilizer. The piping arrangement from the continuous sterilizer to the fermenters will depend somewhat upon the experience of the company as to the number, types, and locations of valves and steam bleeds. However, in general, the piping arrangements of fermenters filled by means of continuous sterilizers are more simplified than batch sterilized systems because all steam bleeding through valves is done in an outward direction. Other types of heat exchangers include those listed below.

Plate Heat Exchangers. The advantages are:

- Plate heat exchangers have a high film coefficient for heat transfer of certain classes of fluids

- The pressure drop across a unit for clear solutions is moderate

The disadvantages are:

- The velocity profile across each plate is not uniform by a factor of five due to the plate corrugations. The friction factors range from 10 to 400 times those in a single pipe with the same port flow rate and with the same surface area. The non-uniformity of flow rates causes suspended solids to accumulate between the plates creating problems of cleaning and sterilizing

- There is a pressure drop through the pressure ports causing an unequal distribution of flow through the plate stack. Solids then begin to accumulate in the plates with the lowest pressure drop until plugging results. Gaskets often leak or rupture

- Plate heat exchangers have the most feet of gasket material for any commercial heat exchanger. The crevices at the gasket have a high incidence of chloride corrosion. Although cooling water may have less than 50 ppm chloride, scale buildup in the gasket crevice usually is several times the concentration in the cooling water. Should the fermentation media contain chlorides as well, stress corrosion will occur from both sides simultaneously. Corrosion due to chlorides is serious when the concentration is above 150 ppm and 80°C. The first evidence of stress corrosion results in non-sterile media, rather than a visible leak or a major leak of water between the two fluids

- Operationally, the plate heat exchanger is more difficult to sterilize and put into operation without losing the back pressure and temperature in the heating section than the concentric pipe exchanger

- The optimum ratio of flow rates for the two fluids is 0.7 to 1.3. This constraint limits the range of media pumping rate

Spiral Heat Exchangers. Spiral heat exchangers have similar problems to the plate type when the gap is small. The velocity profile is better than the plate type. These types of exchangers can be used for media with low suspended solid concentrations and become more the exchanger of choice for continuous sterilizers with high volumetric throughput because the gap becomes larger.

The amount of gasketing material is less than for the plate type resulting in fewer problems.

Shell and Tube Heat Exchangers. The shell and tube exchanger is the least practical choice for cooling fermentation media with high suspended solids. It is very difficult to maintain sterility and cleanliness. It is the easiest to plug and foul.

There is an excellent application for a shell and tube heat exchanger, the continuous sterilization of anti-foam. In this case, the exchanger is not the cooler, but the heater. If the anti-foam liquid has no suspended solids or material which will foul the heating surface, only one exchanger is needed per fermentation building or plant. However, if a crude vegetable oil containing non-triglycerides is the anti-foam agent, then fouling will occur. Figure 7 shows one of the several possible systems for the continuous sterilization of crude vegetable oil. In this case, steam is supplied to the tubes. The main features of the system are two heat exchangers, each having the capacity in their shells to hold oil long enough to sterilize even though the supply pump should run continuously. One heat exchanger is in service while the spare, after being cleaned, is waiting to be put to service when the first can no longer maintain set-point temperature.

With such an anti-foam sterilizer as Fig. 7, a fermentation facility can install a sterile, recirculating, anti-foam system. Commercial anti-foam probes are available and reliable. Frequently, a variable timer is placed in the circuit between the probe and a solenoid valve which permits anti-foam additions to the fermenter. In this manner, anti-foam can be programmed or fed by demand with the ability to change the volume of the addition. It is also possible to place a meter in the sterile anti-foam line of each fermenter in order to control and/or measure the volume added per run.

Small continuous sterilizers are used in fermentation pilot plants as well as for nutrient feeds to a single vessel or group of fermenters.

There are many references in the literature about the theory, design and application of continuous sterilization. For reference, see the following sources and their bibliographies: Peppier, H. J.;[6] Aiba, Humphrey, and Millis;[2] Lin, S. H.™ Ashley, M. H. J., and Mooyman, J.;[9] Wang, D. I. C„ et al.™

Camflex Valve Symbol
Figure 7. Piping and Instrumentation Drawing of a continuous oil (antifoam) sterilizer.

94 Fermentation and Biochemical Engineering Handbook 5.0 FERMENTER COOLING

When designing a fermenter, one primary consideration is the removal of heat. There is a practical limit to the square feet of cooling surface that can be achieved from a tank jacket and the amount of coils that can be placed inside the tank. The three sources of heat to be removed are from the cooling of media after batch sterilization, from the exothermic fermentation process, and the mechanical agitation.

The preceding topic about the design of a continuous sterilizer emphasized reduced turnaround time, easier media sterilization, higher yields and one speed agitator motors. The reduced turnaround time is realized because the heat removal after broth sterilization is two to four times faster in a continuous sterilizer than from a fermenter after batch sterilization. The cooling section of a continuous sterilizer is a true countercurrent design. Cooling a fermenter after batch sterilization is more similar to a cocurrent heat exchanger.

Assuming that all modern large scale industrial fermentation plants sterilize media through a continuous sterilizer, the heat transfer design of the fermenter is only concerned with the removal of heat caused by the mechanical agitator (if there is one) and the heat of fermentation. These data can be obtained while running a full scale fermenter. The steps are as follows:

1. Heat Loss by Convection and Radiation a. Perry's Handbook:114'

(No insulation; if tank is insulated determine proper constant.)

b. Calculate tank surface area = A

Convection and radiation depend upon whether the tanks are insulated or not, and the ambient air temperature, especially during the winter. Measurements of convection and radiation heat losses are, on average, 5% or less of total heat of fermentation (winter and uninsulated tanks).

2. Heat Loss by Evaporation a. If fermenters have level indicators, the average evaporation per hour is easily determined.

b. Calculate pounds of water/hour evaporated from psychometric charts based on the inlet volume and humidity of air used, and at the broth temperature. The exhaust air will be saturated. Determine heat of vaporization from steam tables at the temperature of the broth = HEV = Btu/lb.

Evaporation depends upon the relative humidity of the compressed air, temperature of the fermentation broth and the aeration rate. It is not uncommon that the loss of heat by evaporation is 15 to 25 % of the heat of fermentation. Modern plants first cool the compressed air then reheat it to 70-80% relative humidity based on summertime air intake conditions. Consequently, in winter the air temperature and absolute humidity of raw air are very low and the sterile air supply will be much lower in relative humidity than summer conditions. Therefore, in the winter more water is evaporated from the fermenters than in the summer. (Water can be added to the fermenter or feeds can be made more dilute to keep the running volume equal to summer conditions and productivity in summer and winter equal.)

3. Heat Removed by Refrigerant a. This is determined by cooling the broth as rapidly as possible 5°F below the normal running temperature and then shutting off all cooling. The time interval is then very carefully measured for the broth to heat up to running temperature (A71 and time).

b. Assume specific heat of broth =1.0 Btu/lb-°F

c. Volume of broth by level indicator (or best estimate) = gal g3 = Sp.Ht. x broth vol. * 8.345 x AJ- time (hr) g3 = Btu/hr

4. Heat Added by Mechanical Agitation a. Determine or assume motor and gear box efficiency (about 0.92)

b. Measure kW of motor

5. Heat of Fermentation = AHf

The heat of fermentation is not constant during the course of the fermentation. Peaks occur simultaneously with high metabolic activity. Commercial fermentation is not constant during the course of the fermentation. Commercial fermentations with a carbohydrate substrate may have peak loads of 120 Btu/hr/gal. The average AHf for typical commercial fermentations is about 60 Btu/hr/gal. The average loss of heat due to evaporation from aeration is in the range of 10 to 25 Btu/hr/gal. Fermentations with a hydrocarbon substrate usually have a much higher Af^-than carbohydrate fermentations. Naturally, most companies determine the SHf for each product, especially after each major medium revision. (Typically, data are collected every eight hours throughout a run to observe the growth phase and production phase. Three batches can be averaged for a reliable AHf) In this manner, the production department can give reliable data to the engineering department for plant expansions.

The following is how the heat transfer surface area could be designed for a small fermenter. The minimum heat transfer surface area has been calculated (based on the data below) and presented in Table 2. Assume:

S/S fermenter capacity Agitator

Heat of fermentation (peak) Heat of agitation Heat transfer, U coils Heat transfer, U jacket Safety factor Chilled water supply Chilled water return Broth temperature (28°C)

30,000 gal

15 hp/1,000 gal

100 Btu/hr/gal

38 Btu/hr/gal

120 Btu/hr/sq ft

80 Btu/hr sq ft

No Btu lost in evaporation

Table 2. The Heat Transfer

Surface Area (ft2) Required for Tank with: Coils Only Jacket Only

Mechanical agitation 200 5

Air agitation only 150 6

After the heat transfer surface area requirements are known, various shaped (height to diameter) tanks should be considered. Table 3 illustrates parameters of 30,000 gallon vessels of various H/D ratios.

98 Fermentation and Biochemical Engineering Handbook Table 3. Maximum Heat Transfer Surface

Area Available (ft2) on 80% of the Straight Side


F (ft)




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