WO2002079374A2 - Reglage du volume d'un fermenteur a l'aide d'un additif anti-mousse et informations d'utilisation de l'additif anti-mousse - Google Patents

Reglage du volume d'un fermenteur a l'aide d'un additif anti-mousse et informations d'utilisation de l'additif anti-mousse Download PDF

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WO2002079374A2
WO2002079374A2 PCT/US2002/004278 US0204278W WO02079374A2 WO 2002079374 A2 WO2002079374 A2 WO 2002079374A2 US 0204278 W US0204278 W US 0204278W WO 02079374 A2 WO02079374 A2 WO 02079374A2
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fermentor
defoamer
computer
fermentation
new
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PCT/US2002/004278
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WO2002079374A3 (fr
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Gadi Steiner
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Gadi Steiner
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Publication of WO2002079374A3 publication Critical patent/WO2002079374A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/44—Means for regulation, monitoring, measurement or control, e.g. flow regulation of volume or liquid level
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/02—Means for regulation, monitoring, measurement or control, e.g. flow regulation of foam
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48—Automatic or computerized control

Definitions

  • the present invention relates to a method for controlling the liquid volume within a fermentor. More specifically, the present invention relates to a method for controlling the liquid volume within a fermentor using defoamer and defoamer usage information.
  • Liquid volume within the fermentor fluctuates during fermentation.
  • Foam production poses a large problem. Foam is a mixture of air and liquid in which the liquid is present only in small quantities. Hence, foam is less dense than liquid. This is a disadvantage because of fermentor volume limitations.
  • the foam level within the fermentor is too high, foam is expelled from the fermentor via a fermentor vent. This leads to a loss of fermentor liquid which affects overall desired product production. This can also lead to contamination of the fermentor liquid.
  • fermentation activity occurs in the liquid phase only. Thus, because of the small amounts of fermentor liquid within foam, fermentation activity is very low within foam. Therefore, to maximize the use of fermentor volume during fermentation, the level of foam during fermentation should be minimized.
  • a defoamer is a substance that eliminates foam by increasing the liquid's surface tension.
  • many fermentors simply dispense defoamer on top of the fermentor liquid when foam levels are too high.
  • the user of defoamer does not come without it's drawbacks.
  • the use of too much defoamer can lead to costly purification of the desired product after fermentation.
  • the use of a defoamer can increase the surface tension of the fermentor liquid. This causes small bubbles within the fermentor liquid to collapse to larger bubbles. This, in turn, affects gas-to-liquid oxygen transfer, which is necessary for an efficient fermentation process.
  • defoamer is expensive. Thus, the use of defoamer affects production cost. Accordingly, the use of defoamer should be minimized.
  • the present invention relates to a method for controlling the liquid volume within a fermentor using defoamer and defoamer usage information.
  • fermentor liquid volume is controlled by controlling the drop rate in proportion to the amount of defoamer used during a fermentation run. More specifically, the drop rate is proportional to the fill rate and a variable proportionality factor.
  • the variable proportionality factor is affected by defoamer usage during a fermentation. Defoamer usage is proportional to the recent number of times the fermentor foam or fermentor liquid reached a high fermentor level, the amount of time the defoamer was dispensed during the current fermentation run and the last calculated value of the variable proportionality factor.
  • the variable proportionality factor and the resulting drop rate are periodically updated during the fermentation run.
  • An advantage of the present invention is the maximum use of the fermentor volume.
  • the present invention maximizes the fermentor liquid level during fermentation. This is beneficial because it maximizes the overall yield of the desired product.
  • Another advantage of the present invention is the decreased use of defoamer.
  • Defoamer is costly, can reduce oxygen transfer within the fermentor and can lead to costly purification of the desired product.
  • the decreased use of defoamer is beneficial because it leads to more efficient production of the desired product.
  • Another advantage of the present invention is the maximum use of fermentor liquid.
  • the present invention maximizes the fermentor liquid level during fermentation while minimizing the amount of fermentor liquid expelled due to overflow. This is beneficial because of the cost associated with the fermentor liquid.
  • Fig. 1 is a block diagram illustrating the system architecture of a fermentor, in an embodiment of the present invention.
  • Fig.2 is a flowchart depicting an embodiment of the operation and control flow of the fermentation process, in an embodiment of the present invention.
  • Fig.3 is a flowchart depicting an embodiment of the operation and control flow of the defoamer dispensation process, in an embodiment of the present invention.
  • Fig.4 is a flowchart depicting an embodiment of the operation and control flow of the fermentor liquid volume control process, in an embodiment of the present invention.
  • Fig. 5 is an example computer system and computer program product that can be used to implement the present invention.
  • the present invention relates to a method for controlling fermentor liquid volume using defoamer and defoamer usage information.
  • the present invention allows for a more efficient production of desired products during fermentation while minimizing the use of defoamen
  • fermentor feed or “culture medium” refers to the materials that are used to feed, or otherwise enable the activity of, the organism within the fermentor.
  • Dextrose is an example of a component of fermentor feed.
  • Fermentor medium or “liquid medium” refers to the medium in which the organism within the fermentor resides. Fermentor medium is composed mostly of water and other components that enable the growth of the organism. Ammonia, urea, oxygen, carbon dioxide and defoamer are examples of fermentor medium components.
  • fermentor liquid refers to the liquid that resides within the fermentor.
  • fermentor liquid consists of fermentor feed, fermentor medium and the fermentor organism.
  • fermentor volume refers to the total volume of the fermentor tank.
  • the fermentor tank is the portion of the fermentor that holds the fermentor liquid.
  • fermentor liquid volume refers to the volume of liquid within the fermentor. Since the fermentor liquid is located within the fermentor, fermentor liquid volume is always less than the fermentor volume.
  • defoamer refers to a substance used to eliminate foam. In a fermentor, defoamer is typically dispensed at the top of the fermentor and is applied to the top of the fermentor liquid to decrease foam.
  • fermentation run refers to one complete cycle of a batch, semi- continuous or continuous fermentation.
  • a fermentation run preferably begins when the fermentor is initially filled with starting materials and is inoculated with the proper organisms.
  • a fermentation run preferably ends when the fermentor organisms are no longer active, or when the fermentor is emptied.
  • probe refers to a device located near the top of the fermentor to detect the liquid level or foam level within the fermentor. When the liquid level or foam level within the fermentor reaches the height of the probe and makes contact with the probe, the probe detects the liquid or foam.
  • count refers to an event that occurs when the probe detects liquid or foam within the fermentor. In other words, a count represents an instance when the liquid level or foam level within the fermentor reaches the height of the probe, makes contact with the probe and the event is registered.
  • Drop rate refers to the rate at which liquid volume is flowing out of the fermentor. Drop rate is preferably measured in gallons per minute (gal/min). Liquid typically flows out of the fermentor via a fermentor output line.
  • fill rate refers to the rate at which fermentor liquid, added to the fermentor during the current fermentation run, is flowing into the fermentor. Fill rate is preferably measured in gallons per minute (gal/min). Liquid typically flows into the fermentor via a fermentor input line.
  • STR common stirred-tank reactors
  • STRs with the usual instrumentation for feeding and process monitoring
  • STRs with various types of external or internal cell retention
  • dialysis-membrane reactors cyclone reactors
  • gas-lift reactors gas-lift reactors
  • fluid bed reactors STRs are well- known and the details are not provided here, but will be apparent to one of ordinary skill in the art.
  • the culture medium can be refreshed. While fresh culture medium is pumped into the STR and used broth flows out of the STR, cells can be held back in order to increase biomass and productivity.
  • a membrane cell- recycle system with an external membrane filter connected to an STR can be used in the process of the present invention.
  • An external cross-flow filtration system can also be employed to filter cells.
  • internal cell retention can also be used.
  • an aerated STR can be used which contains a filter module consisting of vertical cylindrical filter rods for total cell retention.
  • a membrane dialysis reactor which operates with total internal cell retention can also be employed.
  • a simple STR under semi-batch, continuous or semi-continuous fermentation can also be employed in the process of the present invention.
  • Steel fermentors operating semi-continuous fermentations are also contemplated.
  • Fig. 1 shows a block diagram illustrating the system architecture 100 of a fermentor, in an embodiment of the present invention.
  • System 100 includes a fermentor 102, fermentor input line 110, fermentor output line 112, defoamer probe 108, defoamer dispenser 109 and fermentor control 114.
  • System 100 also includes fermentor liquid (i.e., broth) 104 and foam 106.
  • Fermentor 102 can be any fermentor commonly used in the art or any fermentor that one of ordinary skill in the art may use for batch, semi-batch, continuous or semi-continuous fermentation.
  • An example of such a fermentor is the MFCS fermentor manufactured by Fermentation Engineering, Inc. of Ripon, California.
  • Fermentor input line 110 can be any valve, pipe or other orifice which is used to introduce a substance into fermentor 102.
  • An example of a substance that can be introduced into fermentor 102 is dextrose, which is fermentor feed necessary for the fermentation process.
  • Input line 110 can be either one such line or multiple lines for introducing multiple and/or various substances into fermentor 102.
  • output line 112 can be any valve, pipe or other orifice which is used to dismiss a substance from fermentor 102.
  • An example of a substance that can be dismissed from fermentor 102 is broth 104, which can occur when the liquid level within fermentor 102 surpasses a threshold.
  • Output line 112 can be either one such line or multiple lines for dismissing substances from fermentor 102.
  • output line 112 and input line 110 are both controlled by fermentor control 114.
  • Defoamer probe 108 is a probe which detects the presence of liquid 104 or foam 106. When the level of liquid 104 or foam 106 within fermentor 102 reaches probe 108, a signal is sent to fermentor control 114. Probe 108 can be any probe which is capable of performing this task or any such probe that may be used by one of ordinary skill in the art to perform this task. Preferably, probe 108 is a conductance probe which constantly measures the conductance of the material in which it is immersed. When probe 108 is suddenly immersed in liquid 104 or foam 106 for a set time, the conductance measured by probe 108 suddenly changes and probe 108 sends a signal to fermentor control 114. After receiving the signal from probe 108, fermentor control 114 may then register the event as a count. This is described in greater detail below.
  • Defoamer dispenser 109 is similar to input line 110. Dispenser 109 dispenses defoamer into fermentor 102. Dispenser 109 is located near the top of fermentor 102 such that dispensed defoamer is sure to fall on foam 106, which rests on the top of liquid 104. This ensures that the defoamer will contact and interact with foam 106. In an embodiment of the present invention, dispenser 109 is controlled by fermentor control 114. Generally, defoamer is dispensed via dispenser 109 as a result of the registration of a count. This is described in greater detail below.
  • Fermentor control 114 is a computer system for controlling all aspects of fermentor 102. Fermentor control 114 controls input line 110, output line 112, probe 108 and dispenser 109. In addition, fermentor control 114 can control any other aspects of fermentor 102 that are typically conducive to centralized control. Fermentor control 114 is described in greater detail below.
  • the processes described in the present invention can use any fermentation method which facilitates the control processes of the present invention.
  • fermentor medium, fermentor feed and fermentor organisms are typically introduced into the fermentation process at the beginning of fermentation run only. The fermentation is then allowed to run its course to yield the desired product batchwise.
  • fermentor feed and/or fermentor medium is added to a fermentor continuously or periodically while withdrawing broth continuously or periodically to maximize the rate of desired product formation.
  • fermentor feed and/or fermentor medium is added to a fermentor continuously or periodically while withdrawing broth continuously or periodically to maximize the rate of desired product formation.
  • the fermentation has a particular cycle time.
  • the processes of the present invention utilize semi-continuous fermentation.
  • fermentor feed can be any "carbohydrate source," i.e, any sugar or starch which is generally used as raw materials for fermentation.
  • carbohydrate sources are those which a lysine-producing bacteria can assimilate. This includes monosaccharides and disaccharides, such as glucose (which is also referred to as dextrose), sucrose and hydrolyzed starch. Dextrose is a preferred form of carbohydrate source.
  • Fermentor feed can also be carbon sources used in a fermentation. Such carbon sources include organic acids, lipids or alcohols, such as glycerol. Fermentor feed can also be nitrogen sources, oxygen and minerals used in a fermentation.
  • C. Medium include organic acids, lipids or alcohols, such as glycerol. Fermentor feed can also be nitrogen sources, oxygen and minerals used in a fermentation.
  • any fermentor medium which is known to one of skill in the art can be used.
  • generally known fermentor media which contain organic and inorganic nutrient sources such as a carbon sources, nitrogen sources and other trace sources can be used in the processes of the present invention.
  • the fermentor organism is fed two sources of nitrogen: an ionized nitrogen source and an un-ionized nitrogen source.
  • the un-ionized sources of nitrogen can be ammonia and urea.
  • the ionized sources of nitrogen can be ammonium phosphate, ammonium acetate, ammonium sulfate and ammonium chloride.
  • the preceding list is not meant to limit the present invention, as any ionized source of nitrogen which accomplishes the tasks of a fermentor medium in the processes of the present invention can be utilized.
  • the process of the present invention can be used in the fermentation of a variety of organisms to produce primary and secondary metabolites, such as amino acids, vitamins, organic acids, emulsifiers and steroids.
  • organisms which produce amino acids namely organisms which are capable of producing L-lysine or L-threonine, are used in the fermentation process.
  • the desired products produced by the process of the present invention can be isolated or purified by conventional means such as chromatography.
  • chromatography For example, affinity or ion exchange chromatography, crystallization and other methods which will be readily apparent to one of ordinary skill in the art can be used to isolate or purify desired products.
  • Fig. 2 shows a flowchart depicting an embodiment of the operation and control flow 200 of the fermentation process of the present invention. It should be noted that control flow 200 is an embodiment of a semi-continuous fermentation process. However, control flow 200 can also apply to semi-batch or continuous fermentation processes. Control flow 200 begins with step 202 and proceeds immediately to step 204.
  • the starting materials are added to fermentor 102.
  • Starting materials are those materials that are initially added to a fermentor to begin the fermentation process.
  • Starting materials can consist of the fermentor organism, such as yeast, the fermentor feed, such as dextrose, and the fermentor medium.
  • Starting materials can be any fermentation starting materials that are commonly used in the art or any such materials that can perform the same function, as is readily determined by one of ordinary skill in the art.
  • step 206 the fermentor liquid volume of fermentor 206 is controlled. In an embodiment of the present invention, this portion of the process is accomplished by fermentor control 114. The manner in which the fermentor liquid volume of fermentor 206 is controlled is described in greater detail below.
  • step 208 materials are added and dropped (i.e, introduced and dismissed) during fermentation.
  • fermentor feed for the fermentor organism
  • the desired product is dropped.
  • step 210 the desired product is removed from fermentor 102.
  • Step 210 generally defines the end of the fermentation run. At this point, the broth is removed and the desired product is extracted form the broth. It should be noted that a continuous fermentation process does not have such an end point. Rather, a continuous fermentation process involves the periodic dropping of the desired product during the fermentation process. Thus, in the instance of a continuous fermentation process, step 210 entails the removal of a portion of the broth in order to extricate the desired product. Therefore, in the instance of a continuous fermentation process, control flows continuously from step 210 to step 206. In step 212, control flow 212 ceases.
  • Fig. 3 shows a flowchart depicting an embodiment of the operation and control flow 300 of the defoamer dispensation process of the present invention.
  • Control flow 300 begins with step 302 and proceeds immediately to step 304.
  • step 304 it is determined whether the requisite time period has passed since the last time the defoamer was dispensed. Because defoaming characteristics of defoamer require some time to react with the foam, it is necessary to allow a time period to pass without responding to probe contact after defoamer is dispensed. This time period allows the defoamer time to react with the foam. After the time period has passed, additional defoamer may be dispensed if fermentor control 114 deems it necessary. In an embodiment of the present invention, the time period is from about one to about ten minutes. In another embodiment of the present invention, the time period is about five minutes. However, the time period may be any period that is deemed adequate to allow the foam to react with the defoamer. If the determination of step 304 is affirmative, controls flows to step 308. Otherwise, control flows to step 306.
  • step 304 If the fermentation process has just begun, i.e, it is time index zero, the determination of step 304 is affirmative. Likewise, the time index is less than the requisite time period, the determination of step 304 is affirmative.
  • control flow 300 allowed defoamer to be dispensed in reaction to a probe signal, regardless of the last time defoamer was dispensed, then additional defoamer may be dispensed without giving the previous defoamer time to react. As described above, this could lead to reduced oxygen transfer and costly purification techniques.
  • step 306 a time increment passes before step 304 is executed again.
  • step 304 determines whether a time period has passed. This determination is executed once for each time increment defined by step 306, until the determination is affirmative.
  • the time increment is one second.
  • the time increment can be any time that is deemed adequate by one of ordinary skill in the art.
  • step 308 it is determined whether foam has been detected by probe 108.
  • step 308 entails probe 108 sending a signal to fermentor control 114, which, in turn, registers the event as a count. Alternatively, the event may be registered as a count by any device that is capable of receiving a signal from probe 108. If the determination of step 308 is affirmative, controls flows to step 312. Otherwise, control flows to step 310.
  • a count is only registered when probe 108 sends a signal to fermentor control 114 and the time period of step 304 has passed. That is, a count can only be registered in step 308 when control of flow 300 is not currently in the loop between steps 304 and 306. This shows that a count is not registered every time probe 108 sends a signal to fermentor control 114. Rather a count is registered when probe 108 sends a signal to fermentor control 114 and the requisite time period has passed since the last time defoamer was dispensed.
  • count data can then be used by fermentor control 114 in determining and controlling fermentor volume control. This is described in greater detail below.
  • step 310 a time increment passes before step 308 is executed again.
  • step 308 determines whether foam has been detected. This determination is executed once for each time increment defined by step 310 until - the determination is affirmative.
  • the time increment is one second.
  • the time increment can be any time that is deemed adequate by one of ordinary skill in the art.
  • the defoamer is dispensed.
  • the defoamer is dispensed via defoamer dispenser 109.
  • the defoamer can be dispensed via any device that is capable of dispensing defoamer onto the foam within fermentor 102.
  • the defoamer is dispensed via defoamer dispenser 109 for a time period, where the time period is from about one to about twenty seconds.
  • the defoamer is dispensed via defoamer dispenser 109 for a time period, where the time period is about seven seconds.
  • the defoamer can be dispensed for any period of time that is adequate to dispense an acceptable amount of defoamer onto the foam within fermentor 102.
  • step 312 control flows directly back to step 304.
  • flow 300 is a continuous process that continues throughout the entire fermentation run.
  • the fermentor liquid volume is dependant on the fill rate and the drop rate. As materials enter and exit fermentor 102 via input lines 110 and output lines 112, the liquid volume of fermentor 102 fluctuates. It can also be seen that the fermentor liquid volume is proportional to the fill rate and inversely proportional to the drop rate. As the fill rate increases, fermentor liquid volume increases. Likewise, as the drop rate increases, fermentor liquid volume decreases. Thus, we see that, generally:
  • X represents other independent aspects of the fermentation process that affect fermentor liquid volume.
  • An example of such an independent aspect is evaporation.
  • the fill rate of fermentor 102 is a variable independent of the fermentor liquid volume control process. That is, the fill rate depends on other aspects of the fermentation process, such as fermentor medium requirements and dextrose concentration.
  • the drop rate must be proportional to the fill rate. This can be gleamed from the fact that the drop rate must mirror the fill rate insofar as the drop rate must keep the fermentor from overflowing and from being underutilized. Likewise, the drop rate must not significantly change fermentor volume. Thus, the drop rate is defined by:
  • A is a variable proportionality factor representing other aspects of the fermentation process that affect fermentor liquid volume (A is explained in greater detail below).
  • the proportionality of equation (2) indicates the following important relationships: 1) the drop rate increases as the fill rate increases and 2) the drop rate decreases as the fill rate decreases. Since the fill rate is independent, the question then turns to how A is defined.
  • A as shown in equation (2), defines the relationship, or level of proportionality, between the drop rate and the fill rate. If A were equal to 1, for example, it could be seen that the drop rate would equal the fill rate and the fermentor liquid volume would generally not increase or decrease. As explained above, it is most efficient to have the highest fermentor liquid volume possible while using a minimal amount of defoamer. Thus, any determinations affecting the fermentor liquid volume should take defoamer usage into account. Therefore, in an embodiment of the present invention, A shall take defoamer usage into account. In an embodiment of the present invention, the following equation defines the manner in which A is calculated during fermentation, while taking defoamer usage into account.
  • a new is calculated periodically, A Iast is the last value of A new , R is a constant percentage decline of A for each calculation cycle, CH is the number of counts registered in the last hour and DM is the number of minutes defoamer has been dispensed during the fermentation run.
  • Equation (3) shows that each calculation of A (i.e., A new ) takes into account the last calculation of A (i.e., A ]ast ). This feature allows for smoother transitions between succeeding values of A, since the old value is taken into account when calculating the new value.
  • A is calculated periodically, where the time period is any time period that is appropriate for the fermentation process. In an embodiment of the present invention, the time period is from about five to about thirty minutes. In another embodiment of the present invention, the time period is about fifteen minutes.
  • the initial determination of A new is made.
  • a prudent value of A last may be used at this time.
  • the value 1.0 is used for A last .
  • the value 1.0 is significant because it indicates that the drop rate is equal to the fill rate (see equation (2)). This value is regarded as a "safe" value because it gives the general assurance that an overflow or an underutilization of fermentor volume will not occur.
  • the initial value can be any value that is deemed adequate by one of ordinary skill in the art.
  • the range of A is from about 0.6 to about 2.0. In another embodiment of the present invention, the range of A is from about 0.6 to about 2.5, if DM is greater than or equal to nine (9) minutes. However, the range of A can be any range that is deemed adequate by one of ordinary skill in the art for any fermentation process.
  • R is a constant representing a percentage decline of A. That is, R represents the percentage that A should decrease each time A is calculated, i.e., R is a reduction constant. It is desirable that A declines slightly upon each such calculation of A in order to guard against under-utilization of fermentor volume. Since the drop rate is proportional to A, a decrease of A over time translates into a decrease of the drop rate over time. This ensures maximum use of the fermentor volume. In an embodiment of the present invention, the value 0.03 is used for R. However, R can be any value that is deemed adequate by one of ordinary skill in the art.
  • CH represents the number of counts registered in the last hour.
  • the registration of counts is described in greater detail above.
  • the number of counts is recorded by fermentor controller 114.
  • CH can be updated immediately upon the registration of a count (see step 308 above) or can be updated periodically.
  • CH is updated periodically, where the period is from about five to about every thirty minutes.
  • CH is updated every fifteen minutes.
  • CH can be updated any time period that is deemed adequate by one of ordinary skill in the art.
  • DM represents the total number of minutes during which defoamer has been released during the current fermentation run. DM is directly related to the number of counts registered during the current fermentation run. As explained above, defoamer is dispensed for a specified period of time (7 seconds in an embodiment of the present invention), each time it is dispensed. Thus, in order to calculate DM, the following equation is used:
  • TC is the total number of counts registered during the current fermentation run and time period is the period of time (in seconds) for which defoamer is dispensed. It is seen that the product of TC and time period is divided by sixty (60) to render a result in the unit of minutes.
  • DM is updated periodically, where the period is from about five to about thirty minutes. In another embodiment of the present invention, DM is updated every fifteen minutes. Alternatively, DM can be updated any time period that is deemed adequate by one of ordinary skill in the art.
  • a new A last * [(1 - 0.03) + (5 * 0.01 * (8/4))]
  • a new A last * [(0.97) + (0.1)]
  • the new value of A will be 7% higher than the previous value of A.
  • the drop rate will increase by 7% over its calculated value fifteen minutes ago.
  • Fig. 4 shows a flowchart depicting an embodiment of the operation and control flow 400 of the fermentor volume control process of the present invention.
  • Control flow 400 applies to fermentation processes, such as some semi-batch, continuous and semi-continuous fermentation processes that allow fermentor volume control.
  • Control flow 400 begins with step 402 and proceeds immediately to step 404.
  • a time period is allowed to pass. This time period allows for fermentation events to occur before volume control is performed. In an embodiment of the present invention, the time period is from about five to about thirty minutes. In another embodiment of the present invention, the time period can be fifteen minutes. However, this time period can be any time period that is adequate to allow fermentation events to occur.
  • step 408 A Iast is set to A new . This feature allows previous values of A to be taken into account when calculating new values of A. This is described in greater detail below.
  • step 410 the variables for equation (3) are evaluated. These variables are CH (counts per hour) and DM (defoamer minutes). As described above, CH is determined by fermentor control 114 during fermentation as counts occur. This is described in greater detail above. DM is determined from count information using equation (4).
  • GOTO SPK1A IF (ST07 ⁇ 1800)&(PHIF31FM:CB_OTVL:2 ⁇ 25.0) THEN ;after ;40 min or 25% out on NH3 valve the shot will be done GOTO SPK1A
  • TIMERCLR ST08 zeros out minimum time between shots timer
  • LET MF31BIA:AI-INVL:0 PHIF31FGB:CAL-VEVL:2 + PHIF31FGB:CAL-VFVL:2 TIMERCLR ST07 TIMERON ST07
  • PRINT 1 "MF%i SECOND SPIKE",IN11 ;prints out when second spike ;occurred SPK2A: WAIT 3
  • WAIT 5 LET MF31BTA:AI - INVL:0 PHIF31FGB:CAL-VEVL:2 + PHIF31FGB:CAL-VFVL:2 increases bias during shot
  • TIMERCLR ST08 zeros out minimum time between shots timer
  • the invention is implemented primarily in firmware and/or hardware using, for example, hardware components such as application specific integrated circuits (ASICs).
  • ASICs application specific integrated circuits

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Abstract

L'invention concerne un procédé de réglage du volume de liquide dans un fermenteur à l'aide d'un additif anti-mousse, et des informations d'utilisation de l'additif anti-mousse. La nature de ce procédé permet de produire plus efficacement les produits désirés. Le volume de liquide du fermenteur est réglé par régulation du taux d'écoulement proportionnellement à la quantité d'additif anti-mousse utilisée au cours d'un cycle de fermentation. Plus spécifiquement, le taux d'écoulement est proportionnel au taux de remplissage et à un facteur de proportionnalité variable. Le facteur de proportionnalité variable est affecté par l'utilisation de l'additif anti-mousse au cours d'une fermentation. L'utilisation de l'additif anti-mousse est proportionnel au nombre de fois récent que la mousse du fermenteur ou le liquide du fermenteur ont atteint un niveau élevé, le nombre de fois que l'additif anti-mousse a été distribué au cours de la fermentation actuelle et la dernière valeur calculée du facteur de proportionnalité variable. Le facteur de proportionnalité variable et le taux d'écoulement obtenu sont périodiquement mis à jour pendant le cycle de fermentation.
PCT/US2002/004278 2001-03-30 2002-02-14 Reglage du volume d'un fermenteur a l'aide d'un additif anti-mousse et informations d'utilisation de l'additif anti-mousse WO2002079374A2 (fr)

Applications Claiming Priority (2)

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US27968001P 2001-03-30 2001-03-30
US60/279,680 2001-03-30

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WO2002079374A2 true WO2002079374A2 (fr) 2002-10-10
WO2002079374A3 WO2002079374A3 (fr) 2004-03-18

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
WO2015109192A1 (fr) * 2014-01-16 2015-07-23 Life Technologies Corporation Systèmes capteurs de mousse de réacteur, et procédés d'utilisation

Citations (4)

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US3672953A (en) * 1970-02-09 1972-06-27 Mobil Oil Corp Process for growing cells of a microorganism on a carbon-containing liquid substrate
GB1470861A (en) * 1974-03-08 1977-04-21 Pfizer Ltd Process of controlling foaming in continuous fermentations
US5593890A (en) * 1992-10-23 1997-01-14 Centro de Investigaci on y de Estudios Avanzados del Instituto Polit ecnico Nacional Apparatus suitable for conducting gas-liquid reactions
US6029101A (en) * 1996-11-18 2000-02-22 Scius Corporation Process control system user interface

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Publication number Priority date Publication date Assignee Title
US3672953A (en) * 1970-02-09 1972-06-27 Mobil Oil Corp Process for growing cells of a microorganism on a carbon-containing liquid substrate
GB1470861A (en) * 1974-03-08 1977-04-21 Pfizer Ltd Process of controlling foaming in continuous fermentations
US5593890A (en) * 1992-10-23 1997-01-14 Centro de Investigaci on y de Estudios Avanzados del Instituto Polit ecnico Nacional Apparatus suitable for conducting gas-liquid reactions
US6029101A (en) * 1996-11-18 2000-02-22 Scius Corporation Process control system user interface

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Title
JENKINS R O: "INTEGRATED SOFTWARE FOR FERMENTATION PROCESS CONTROL USING A FLEXIBLE LOW-COST INTERFACE" BINARY COMPUTING IN MICROBIOLOGY, vol. 3, no. 4, 1991, pages 118-120, XP008025109 ISSN: 1057-350X *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015109192A1 (fr) * 2014-01-16 2015-07-23 Life Technologies Corporation Systèmes capteurs de mousse de réacteur, et procédés d'utilisation
US9606077B2 (en) 2014-01-16 2017-03-28 Life Technologies Corporation Reactor foam sensor systems and methods of use
US10302581B2 (en) 2014-01-16 2019-05-28 Life Technologies Corporation Reactor foam sensor systems and methods of use

Also Published As

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