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Animal cell bioreactors are used to grow animal cells under controlled conditions for large scale production of products like monoclonal antibodies, hormones, and vaccines. Bioreactors maintain a homogeneous environment through constant stirring and control of temperature, pH, and oxygen levels. They can grow both suspended and immobilized cells. Common bioreactor types include stirred tank, airlift, microcarrier, encapsulation, hollow fiber, perfusion, and packed bead reactors. Each has advantages for growing different types of anchorage-dependent or anchorage-independent cells.
Animal cell bioreactors are used to grow animal cells under controlled conditions for large scale production of products like monoclonal antibodies, hormones, and vaccines. Bioreactors maintain a homogeneous environment through constant stirring and control of temperature, pH, and oxygen levels. They can grow both suspended and immobilized cells. Common bioreactor types include stirred tank, airlift, microcarrier, encapsulation, hollow fiber, perfusion, and packed bead reactors. Each has advantages for growing different types of anchorage-dependent or anchorage-independent cells.
Animal cell bioreactors are used to grow animal cells under controlled conditions for large scale production of products like monoclonal antibodies, hormones, and vaccines. Bioreactors maintain a homogeneous environment through constant stirring and control of temperature, pH, and oxygen levels. They can grow both suspended and immobilized cells. Common bioreactor types include stirred tank, airlift, microcarrier, encapsulation, hollow fiber, perfusion, and packed bead reactors. Each has advantages for growing different types of anchorage-dependent or anchorage-independent cells.
Interest in the in vitro cultivation of animal cells has developed
because of the need for large scale production of monoclonal antibodies, hormones, vaccines and other products What is Bioreactor? • An apparatus for growing organisms (yeast, bacteria, or animal cells) under controlled conditions. • Used in industrial processes to produce pharmaceuticals, vaccines, or antibodies • Also used to convert raw materials into useful by products such as in the bioconversion of corn into ethanol. • Bioreactors supply a homogeneous (same throughout) environment by constantly stirring the contents. • Bioreactors give the cells a controlled environment by ensuring the same temperature, pH, and oxygen levels. Required properties of bioreactors • Simplicity of design • Large number of organisms per unit volume • Uniform distribution of micro-organisms • Simple and effective oxygen supply • Low energy requirement • Uniform distribution of energy • providing information about the formation of 3D tissue Organisms growing in bioreactors may be: • Suspended/Anchorage independent • Immobilized/Anchorage dependent . A simple method, where cells are immobilized, is Conditions imposed by the bioprocess Petri dish with agar gel. Large scale immobilized cell bioreactors are: • moving media, also known as Moving Bed Biofilm Reactor (MBBR); • Packed bed; • Fibrous bed; • Membrane. Anchorage Dependent cells • Anchorage dependent cells: These cells require a solid support for their replication. They produce cellular protrusions (pseudopodia) which allow–Require surface attachment to grow them to adhere to positively charged surfaces and often grow as monolayer.
• Anchorage independent cells: These cells do not require a
support and can grow as a suspension in submerged culture. Established and transformed cell lines are normally in this category Modified Stirred fermenter • The modifications made to fermenters are to reduce the possibility of cell damage due to shear, heat or contamination. • Marine propellers revolving at a slow speed (10 to 100 rpm) will normally provide adequate mixing. • Hemispherical bottoms on the vessels will ensure better mixing of the broth at slow stirrer speeds. • Water jacket heating is often preferred since heating probes may give rise to localized Range of culture apparatus for zones of high temperature which might suspension cells (A) magnetic bar damage some of the cells. spinner culture, (B) Techne MCS • Magnetic driven stirrers may be used to stirrer, (C) surface stirrer , (D) small reduce the risk of contamination. scale fermenter with marine impeller, (E) airlift fermenter, (F) vibro-fermenter . Air lift fermenter Air-lift fermenters have proved ideal for growth of some cell lines because of the gentle mixing action and reduced shear forces when compared with those in stirred vessels. The absence of a stirrer and associated seals excludes a potential source of contamination Example :monoclonal Range of culture apparatus for suspension antibodies production from cells (A) magnetic bar spinner culture, (B) hybridoma cells Techne MCS stirrer, (C) surface stirrer , (D) small scale fermenter with marine impeller, (E) airlift fermenter, (F) vibro- fermenter . Microcarriers • Microcarriers may provide a solution to growing anchorage-dependent cultures by providing the necessary surface for attachment. • Animal cells normally have negative surface charge and will attach to a charged surface by electrostatic forces. • DEAE Sephadex A-50 resin beads and number of microcarrier beads, manufactured from dextran, cellulose, gelatin, plastic or glass, are commercially available and used. Encapsulation • Encapsel, a technique developed by Damon Biotechnology, U.S.A.,traps the animal cells in sodium alginate spheres which are then coated with polylysine to form a semi-permeable membrane. The enclosed alginate gel is solubilized with sodium citrate to release the cells into free suspension within the semipermeable coat. • The cells are entrapped in calcium alginate or agarose beads which will allow high molecular weight products to diffuse into the medium Hollow fibre chambers • Anchorage dependent cells cultured in the bundles of hollow fibres held together in cartridge chambers. • The cells are grown in the extra capillary spaces (ECS) within the cartridge. • Medium and gases diffuse through from the capillary lumea to the ECS. • Monoclonal antibodies, viruses, gonadotropin, insulin and antigens Perfusion Culture
• High density culture
• Product can be harvested
continuously
• High productivity
• Dilution rate not limited
• Separation of viable and dead
cells possible Packed glass bead reactors
•Packed glass bead reactors have
proved to be useful for long term culture of attached dependent cell lines. • Increasing the size of vessels causes problems with mass transfer of oxygen and nutrients and scale up can be achieved by increasing the number of small vessels.