Fed-batch

Fed-batch

Overview
A fed-batch is a biotechnological batch
Batch
Batch may refer to:Food and drink*Batch , an alcoholic fruit beverage*Batch loaf, a type of bread popular in Ireland*A dialect term for a bread roll used in Nuneaton and Coventry, England*Small batch, bourbon whiskey blended from selected barrels...

 process which is based on feeding of a growth limiting nutrient substrate to a culture.
The fed-batch strategy is typically used in bio-industrial processes to reach a high cell density in the bioreactor
Bioreactor
A bioreactor may refer to any manufactured or engineered device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. This...

.
Mostly the feed solution is highly concentrated to avoid dilution of the bioreactor.
The controlled addition of the nutrient directly affects the growth rate of the culture and allows to avoid overflow metabolism
Crabtree effect
Named after the English biochemist Herbert Grace Crabtree, the Crabtree effect describes the phenomenon whereby the yeast, Saccharomyces cerevisiae, produces ethanol aerobically in the presence of high external glucose concentrations rather than producing biomass via the tricarboxylic acid cycle,...

 (formation of side metabolites, such as acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...

 for Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

, lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

 in cell cultures, ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 in Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

), oxygen limitation (anaerobiosis).

Substrate limitation offers the possibility to control the reaction rates to avoid technological limitations connected to the cooling of the reactor and oxygen transfer.
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Encyclopedia
A fed-batch is a biotechnological batch
Batch
Batch may refer to:Food and drink*Batch , an alcoholic fruit beverage*Batch loaf, a type of bread popular in Ireland*A dialect term for a bread roll used in Nuneaton and Coventry, England*Small batch, bourbon whiskey blended from selected barrels...

 process which is based on feeding of a growth limiting nutrient substrate to a culture.
The fed-batch strategy is typically used in bio-industrial processes to reach a high cell density in the bioreactor
Bioreactor
A bioreactor may refer to any manufactured or engineered device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. This...

.
Mostly the feed solution is highly concentrated to avoid dilution of the bioreactor.
The controlled addition of the nutrient directly affects the growth rate of the culture and allows to avoid overflow metabolism
Crabtree effect
Named after the English biochemist Herbert Grace Crabtree, the Crabtree effect describes the phenomenon whereby the yeast, Saccharomyces cerevisiae, produces ethanol aerobically in the presence of high external glucose concentrations rather than producing biomass via the tricarboxylic acid cycle,...

 (formation of side metabolites, such as acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...

 for Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

, lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

 in cell cultures, ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 in Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

), oxygen limitation (anaerobiosis).

Substrate limitation offers the possibility to control the reaction rates to avoid technological limitations connected to the cooling of the reactor and oxygen transfer. Substrate limitation also allows the metabolic control, to avoid osmotic effects, catabolite repression
Catabolite repression
Carbon catabolite repression, or simply catabolite repression, is an important part of global control system of various bacteria and other micro-organisms. Catabolite repression allows bacteria to adapt quickly to a preferred carbon and energy source first...

and overflow metabolism of side products.

Different strategies can be used to control the growth in a fed-batch process:
Control Parameter Control Principle
DOT (pO2) DOstat (DOT= constant), F~DOT
Oxygen uptake rate (OUR) OUR=constant, F~OUR
Glucose on-line measurement of glucose (FIA), glucose=constant
Acetate on-line measurement of acetate (FIA), acetate=constant
pH (pHstat) F~pH (acidification is connected to high glucose)
Ammonia on-line measurement of ammonia (FIA), ammonia=constant
Temperature T adapted according to OUR or pO2