[Introduction] Bioreactors and downstream processing

Biotechnology is the culmination of more than 8000 years of human experience using living organisms and the process of fermentation to make products such as bread, cheese, beer and wine. Today biotechnology is applied to manufacturing processes used in health care, food and agriculture. A widely accepted definition of Biotechnology is "Application of scientific and engineering principles to processing of materials by biological agents to provide goods and service". Some other definitions replace rather ambiguous word ‘biological agents’ with more specific words such as microorganisms, cells, plant and animal cells and enzymes. The entire process can be divided in three stages.

Stage I : Upstream processing which involves preparation of liquid medium, separation of particulate and inhibitory chemicals from the medium, sterilization, air purification etc.

Stage II: Fermentation which involves the conversion of substrates to desired product with the help of biological agents such as microorganisms. 

Stage III: Downstream processing which involves separation of cells from the fermentation broth, purification and concentration of desired product and waste disposal or recycle.

A fermentation process requires a fermenter or bioreactor for successful production because it provides the following facilities for the process such as contamination free environment, specific temperature maintenance, maintenance of agitation and aeration, pH control, monitoring Dissolved Oxygen (DO), ports for nutrient and reagent feeding, ports for inoculation and sampling, fittings and geometry for scale up, minimize liquid loss and growth facility for wide range of organisms. The definition of bioreactor is “Bioreactor is a vessel in which a chemical process is carried out which involves organisms (mainly microbes-viruses or bacteria, fungi and yeasts) or biochemically active substances (enzymes, e.g.) derived from such organisms.” This process can either be aerobic or anaerobic. Traditionally designated as “Fermenters”

The environmental conditions of a bioreactor like gas (oxygen, nitrogen, carbon dioxide) and liquid flow rates, temperature, pH, concentration of substrate and products, cells number and their composition (proteins and nucleic acids), dissolved oxygen levels, and agitation speed (or circulation rate) need to be closely and continuously monitored and controlled. In many cases, strictly aseptic conditions have to be maintained. In an aerobic process, optimal oxygen transfer is perhaps the most difficult task to accomplish because there are limits to the speed of agitation, for maintaining high power consumption and to the damage to organisms caused by excessive tip speed.

The general requirements of the bioreactor are as follows: 

(a) The design and construction of bioreactors must be such that sterile conditions are maintained. Furthermore, monoseptic conditions should be maintained during the fermentation and ensure containment. 

(b) Optimal mixing with low, uniform shear must be achieved by proper designing of agitator and aerator 

(c) Adequate mass transfer (oxygen) must be achieved by monitoring the speed of agitator. 

(d) Clearly defined flow conditions must be maintained by proper opening valves and monitoring devices. 

(e) Feeding of substrate must be maintained with prevention of under or overdosing by proper feed ports.

 (f) Suspension of solids and gentle heat transfer. 

(h) Compliance with design requirements such as: ability to be sterilized; simple construction; simple measuring, control, regulating techniques; scaleup; flexibility; long term stability; compatibility with up- downstream processes; antifoaming measures.