With the development of genetic engineering, a lot of highly effective drugs, sensitive diagnostic reagents and biotechnological products have been made through animal cell culture. At present, this field is becoming a high-tech industry.
Animal cells are very different from microbial cells. They have strict needs for in vitro culture. For example, animal cells are very sensitive to shear stress. So reactor designs cannot use the high shear force that is used for microbial cell culture.
So traditional microbial cell reactors must be changed to work for animal cell culture. It is very important and urgent to develop new bioreactors based on the features of animal cells.
一、Process of Animal Cell Culture
Introduction to Animal Cell Culture
Animal cell culture is a technique. It takes cells from animal bodies, breaks them into single cells, copies the in vivo growth environment, and lets the cells survive, grow, multiply and keep their structure and function in vitro. The conditions are sterile, proper temperature and rich nutrients.
In vitro culture has two types: primary culture and subculture. Primary culture is the first time to culture cells taken from a living organism. Cells that multiply about 10 generations in culture are called primary cells. The next step of transferring and culturing cells from primary culture is called subculture.
Principles of Animal Cell Culture
The principle of animal cell culture is cell proliferation. The process takes related tissues from an animal body, breaks them into single cells (using trypsin or collagenase), puts the cells in a suitable medium, and lets these cells grow and multiply. Cell culture means the growth of cells in vitro. Animal cells do not grow into whole organisms when cultured as single cells.
The nutrients needed for in vitro cell culture are almost the same as those in the body. For example, they need sugar, amino acids, inorganic salts, growth-promoting factors and trace elements. A medium made by mixing these substances strictly by their types and needed amounts is called a synthetic medium. Some parts of the internal environment for animal cells are not fully understood yet. So people need to add animal serum to provide an environment like the one in a living organism. So natural parts like serum and plasma are usually added when using synthetic media.
二、Types of In Vitro Animal Cell Culture
- Suspension Culture
Suspension culture is the process where cells grow freely in a culture vessel. It is mainly used for anchorage-independent cells. These cells do not need to attach to a surface for in vitro growth. People can culture them in suspension with methods used for microbes.
Cells from blood and lymph tissues, many tumor cells (including hybridoma cells) and many recombinant cells are in this group. They grow in suspension, so the cell density is usually high. It is easy to produce them on a large scale and control the process.
- Adherent Culture
Adherent culture is a cell culture method. Cells must attach to the surface of a solid substrate to grow. It is mainly used for anchorage-dependent cells (also called adherent cells). Most animal cells are in this type.
These cells need to attach to some solid or semi-solid surfaces with proper positive charges to grow. After attaching and growing, the cells lose their original shape. Their shapes usually become similar. The main types are fibroblast-like, epithelial-like, migratory and polymorphic.
- Immobilized Culture
Immobilized culture is an entrapment culture method. It works for both anchorage-dependent and anchorage-independent cells. It has advantages like high cell density, strong shear resistance and good contamination resistance.
The immobilization method is different based on the cells being cultured. Generally, collagen entrapment is used for anchorage-dependent cells. Calcium alginate entrapment is often used for anchorage-independent cells. Common cell immobilization methods are adsorption, covalent attachment, ionic/covalent cross-linking, entrapment and microencapsulation.
三、Bioreactors for Animal Cell Culture
Large-scale animal cell culture needs special bioreactors. Animal cells are different from microbial and plant cells. They have no cell wall outside. Their plasma membranes are fragile. They are sensitive to shear stress and have strict needs for the in vitro culture environment.
So traditional reactors for microbial fermentation cannot be used for large-scale animal cell culture. The design or change of such reactors must follow these rules: low shear effect, good transfer effect and proper mechanical properties.
Since the 1970s, bioreactors for cell culture have developed a lot. There are more types and larger scales. But the main structural types of reactors are still stirred-tank, airlift and fixed-bed bioreactors.
Except for cultures for artificial mutagenesis, the design rule of bioreactors for animal cell culture is to copy the in vivo growth environment of the cultured cells as much as possible. Animal cells have special growth features. So people need to pay special attention to reactor structure design and the choice of special carriers.
Common bioreactors for animal cell culture include: airlift bioreactors, hollow fiber bioreactors, fluidized-bed bioreactors, stirred-tank bioreactors, packed-bed bioreactors, single-use bioreactors and membrane bioreactors.
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About Ferbio
Ferbio boasts extensive experience in the manufacturing of various bioreactors and pressure vessels. We have assembled a team of experts specializing in bioreaction engineering, fermentation technology, mechanical manufacturing, and automatic control. Our research and technological capabilities maintain a leading position domestically and a world-class standard internationally, delivering products that ensure customers a satisfying, reliable, and reassuring experience