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The secret of ultra-high cell density: How to achieve optimal performance in bioreactors?
In today's world of biotechnology, the choice of culture technique is critical to the yield and quality of the finished product. Among them, fed-batch culture has received widespread attention because it can effectively control nutrients during the culture process and promote the growth and development of microorganisms. This technology not only increases yields but also avoids some of the limitations of traditional batch cultures.
Fed-batch culture is defined as an operating technique that continuously supplies one or more nutrients to the bioreactor during the culture process and keeps the product unchanged in the reactor until the end of the culture.
Fed-batch cultures offer significant advantages over conventional full batch cultures, particularly when controlling nutrient concentrations to influence the yield or productivity of desired metabolites. Through precise nutrient supply, researchers can effectively limit the production of unnecessary metabolic byproducts within cells, thereby increasing the density of desired cells.
Main types of fed-batch cultures
Fed-batch cultures have a wide range of applications and can be adapted to different bioprocesses. Here are some effective fed-batch culture strategies:
1. Matrix inhibitionMany microorganisms are inhibited by high concentrations of nutrients (such as methanol, ethanol and acetic acid). In fed-batch cultures, timely addition of these substrates can shorten lag times and reduce inhibitory effects on cell growth.
2. High cell densityCompared to traditional batch culture, in order to achieve a higher cell concentration, fed batch culture requires controlling the concentration of nutrients in the culture medium so as not to inhibit the growth of microorganisms.
3. Glucose effectIn the production of baker's yeast, even under sufficient dissolved oxygen conditions, excess sugar will cause alcohol to be produced, thereby inhibiting cell growth. The feeding batch process can effectively reduce this effect and improve the overall productivity of yeast.
4. Catabolism suppressionProviding a rapidly metabolized carbon source (such as glucose) will increase the concentration of ATP in the cell, thereby inhibiting the synthesis of certain enzymes. Fed batch culture can maintain low concentrations of glucose and promote enzyme synthesis.
5. Use of helper mutants
For microbial mutants that require additional nutrients, proper control of the concentration of essential nutrients can effectively promote the production of required metabolites.
By controlling the feed rate and precisely managing the supply of nutrients, the production capacity of the cells and the concentration of the desired product can be maximized.
Strategies for fed-batch culture
When implementing fed-batch cultures, there are several key strategies that help ensure optimal performance of the culture process:
High cell density culture
This strategy is frequently used in bioindustrial processes to achieve high cell densities within bioreactors.
Continuous fed batch culture
In this type of fed-batch culture, the growth-limiting substrate supply rate is constant, which can maintain the stability of the culture process.
Exponentially fed batch culture
Under ideal conditions, cells grow at an exponential rate. This culture format allows the supply rate of growth-limiting substrate to be increased in proportion to the rate of cell growth.
Future biotechnology developments will further explore the potential of these fed-batch culture strategies to produce more valuable bioproducts at higher cell densities. However, how to balance efficiency and production costs in industrial applications is still a question worth exploring?
