Fermentation Design every 12 or 24 hours such as a nitrogen source;(ii) a large volume carbohydrate solution fed continuously, perhaps varying with the fermenter olume, (iii precursor feed, fed in small amounts relative to assay data; (iv) anti-foam( Some companies prefer a separate anti-foam feed system for each fermenter. A continuously sterilizing systemfor anti-foam is discussed below which is capable of servicing all the fermenters. ) /v other tanks for ac bases, salts, etc. Many companies prefer to batch sterilize a known qu and transfer the entire contents quickly. Sometimes, the feeds require programming the addition rate to achieve high productivity. In this latter case, large volume tanks are used and the contents are presterilized ( batch or continuous)or the feed is continuously sterilized between the feed tank and the fermenter. Usually feed tanks are not designed as fermenters, even though they are sterilizable, and there is no need for high volume air flow, but only sufficient air pressure for the transfer. For solvablenutrients the agitator and anti-foam system are not required Since the air requirements are needed only to transfer the feed, the air piping design is different and the sterile air filter is proportionately smaller. Instrumentation is usually limited to temperature, pressure and volume. The H/D ratio ofthe vessel can be near one foreconomy and need not be designed for the aeration/agitation requirements of a fermenter 2. 8 Sterile Filters Sterile air filtration is simple today with the commercial units readily available. However, some companies still design their own(see Aiba, Humphrey and Millis 2 )to use a variety of filter media such as carbon cotton,glass staple, etc. (For recent papers about industrial applications of artridge filters, see Bruno 3I and Perkowski. 14) The essential method to obtain sterile air, whether packed-bed or cartridge filters are used, is to reduce the humidity ofthe airafter compression so that the filter material always remains dry. The unsterilized compressed air must neverreach 100%relative humidity. Largerplants install instrumen- tation with alarms set at about 85% relative humidity Careful selection of the cartridge design or the design of packed-bed filters will result in units that can operate in excess of three years without replacement of filter media. If a fiber material is used in a packed-bed type filter, the finer the fiber diameter the shallower the bed depth needs to be for efficient filtration. Other filter media are less common and tend to have special problems and/or shorter life The bed depth of filters is only 10 to 18 inches for fibers of less than 1( microns. These filters run"clean"for 2 weeks or longer before being resterilizedFermentation Design 75 every 12 or 24 hours such as a nitrogen source; (ii) a large volume carbohydrate solution fed continuously, perhaps varying with the fermenter volume; (iii) aprecursor feed, fed in small amounts relative to assay data; (iv) anti-foam (Some companies prefer a separate anti-foam feed system for each fermenter. A continuously sterilizing system for anti-foam is discussed below which is capable of servicing all the fermenters.); (v) other tanks for acids, bases, salts, etc. Many companies prefer to batch sterilize a known quantity and transfer the entire contents quickly. Sometimes, the feeds require programming the addition rate to achieve high productivity. In this latter case, large volume tanks are used and the contents are presterilized (batch or continuous) or the feed is continuously sterilized between the feed tank and the fermenter. Usually feed tanks are not designed as fermenters, even though they are sterilizable, and there is no need for high volume air flow, but only sufficient air pressure for the transfer. For solvable nutrients the agitator and anti-foam system are not required. Since the air requirements are needed only to transfer the feed, the air piping design is different and the sterile air filter is proportionately smaller. Instrumentation is usually limited to temperature, pressure and volume. The Hn> ratio ofthe vessel can be near one for economy and need not be designed for the aeratiodagitation requirements of a fermenter. 2.8 Sterile Filters Sterile air filtration is simple today with the commercial units readily available. However, some companies still design their own (see Aiba, Humphrey and Millisr2]) to use a variety of filter media such as carbon, cotton, glass staple, etc. (For recent papers about industrial applications of cartridge filters, see Bruno[3] and Perkowski.r4]) The essential method to obtain sterile air, whether packed-bed or cartridge filters are used, is to reduce the humidity ofthe air after compression so that the filter material always remains dry. The unsterilized compressed air must never reach 100% relative humidity. Largerplants install instrumen￾tation with alarms set at about 85% relative humidity. Carehl selection of the cartridge design or the design of packed-bed filters will result in units that can operate in excess of three years without replacement of filter media. If a fiber material is used in a packed-bed type filter, the finer the fiber diameter the shallower the bed depth needs to be for efficient filtration. Other filter media are less common and tend to have special problems and/or shorter life. The bed depth of filters is only 10 to 18 inches for fibers of less than 10 microns. These filters run “clean” for 2 weeks or longer before being resterilized