Due to increasing developments in the biotechnological processing and bioreactor industry, there has besides been an addition in the figure of bioreactors presently available ( See Fig. 1 ) ( Oksman-Caldentey et al. , 2002 ) . The chief map of a properly designed bioreactor is to supply a controlled environmental status at which microorganisms can be able to execute the needed reactions and transmutations in the most optimal efficiency possible and achieve optimal growing and/or merchandise formation ( Chisti, 1989 ; Najafpour, 2007 ) .
Figure 1: Bioreactor categorization ( Oksman-Caldentey, et al. , 2002 )
For aerophilic bioprocesses the O mass transportation is frequently the critical modification factor in supplying the optimum environment due to the low solubility of O in the medium ( Chisti, 1989, Garcia-Ochoa and Gomez, 2009 ) . Agitation is widely used to supply for higher gas-liquid interfacial country due to the higher shear field and besides better liquid-liquid/liquid-solid mass transportation. Under fortunes of agitation, sufficient conveyance rates need to be attained. Nevertheless, in general bioreactor design, other operational demands such as unfertile operation, power ingestion and economic sciences are considered ( Chisti, 1989 ) .
For aerophilic bioprocesses the Stirred armored combat vehicle reactors ( STR ) has been the most normally used type of biochemical reactor ( Chisti, 1989, Garcia-Ochoa and Gomez, 2009 ) . The STR has successfully been applied to procedures such as aerophilic agitation and effluent intervention, among others ( Garcia-Ochoa and Gomez, 2009 ) . Nevertheless, with STR still the most regular industrial bioreactor used for aerophilic procedures, auxiliary reactors such as pneumatically driven reactors ( e.g. the airlift reactors ( ALR ) ) have been developed to antagonize the restrictions of the moved armored combat vehicle and other automatically agitated reactors ( Chisti, 1989 ) .
STIRRED TANK REACTOR
Moved armored combat vehicles, or conventional fermenters, have been widely used for culturing suspension cells since the sixtiess. Mixing and bubble scattering in a STR is achieved by mechanical agitation ( Doran, 2009 ) . Assorted different impeller forms and sizes are used to bring forth different flow forms within the vas ( Doran, 2009 ) . The impeller is frequently mounted at the top of the bioreactor to drive the liquid downward in large-scale cell civilization bioreactors. Baffles are used in the STR to cut down vortexing ( Doran, 2009 ) .
The aspect ratio of STRs ( i.e. ratio of tallness to diameter ) can be varied. The most economical STR form would hold an aspect ratio of 1 as it has the smallest surface to volume ratio ( Doran, 2009 ) . When aeration is required, the facet ratio is increased, and therefore provides for longer contact times between the gas and liquid as a greater hydrostatic force per unit area is produced at the underside of the vas ( Doran, 2009 ) . Temperature and heat transportation is controlled via internal chilling spirals.
In these systems, a high figure of variables influence the mass transportation and commixture, but the most of import among them are stirrer velocity, type and figure of scaremongers and gas flow rate used ( Garcia-Ochoa, 2009 ) .
Figure 2: Typical Stirred Tank Reactor for Aerobic Culture ( Doran, 2009 )
Airlift cringle reactors have emerged as one of the most promising devices in chemical, biochemical and environmental technology operations ( Tongwang, 2006 ) .
Airlift reactors are pneumatically goaded reactors in which the energy input required for commixture is through a steam of gas or air, without any mechanical agitation ( Oksman-Caldentey, et al. , 2002 ; Najafpour, 2007 ) . The air-driven bioreactor is equipped with a sparger at the underside of the vas ( Vogel, 1997 ) . It is widely used to civilization delicate cells such as hybridoma cells, works cell, tissue, and organ civilizations ( Flickinger, et al. , 1999 ; Vogel, 1997 ) .
The ALR consist of two tubings ( Flickinger, et al. , 1999 ) . Air is introduced in the underside of one tubing through a sparger pealing up to the portion of the vas cross subdivision called the riser ( Flickinger, et al. , 1999 ; Najafpour, 2007 ) . The gas and liquid travels upward as a two-phase co-current flow ( Siegel et al. , 1992 ) . The riser is where most of the mass transportation takes topographic point and has the higher gas armed robbery ( Siegel et al. , 1992 ) . As the air bubbles rise to the top of the riser, gas is held up, unstable denseness decreases doing liquid in the riser to travel upwards and the bubble-free liquid to go around through the downcomer ( Najafpour, 2007 ; Flickinger, et al. , 1999 ) . The ensuing difference in the denseness of the liquid in the riser relation to the annulate infinite within the bioreactor ( the downcomer ) causes fluctuations in the commixture and kineticss of the fluid, which are greatly influenced by the viscousness, denseness difference, gas flow and gas bubble size ( Oksman-Caldentey, et al. , 2002 ) . The denseness difference between riser and down-comer enables the liquid medium and cells to go around with high turbulency ( Najafpour, 2007 ; Oksman-Caldentey, et al. , 2002 ) .
The usage of draft tubing divides the flow in a riser and downcomer. ( Oksman-Caldentey, et al. , 2002 ) . The flow passes up through the draft tubing to the headspace of the bioreactor, where the extra air and the byproduct disengage ( Najafpour, 2007 ) . The extent of gas detachment will deeply act upon the gas armed robbery, liquid circulation speed and mass transportation of ALRs ( Siegel et al. , 1992 ) . Cooling can be provided by either doing the draft tubing an internal heat money changer or with a heat money changer in an external recirculation cringle ( Najafpour, 2007 ) .
The gas is normally injected by inactive ( diffuser rocks, noses, perforated home bases ) or dynamic gas distributers ( slot noses, Venturi tubings, injectors or ousters ) ( Oksman-Caldentey, et al. , 2002 ) .
There are three common airlift constellations, which are the internal cringle airlift reactor, the external cringle airlift reactor and the draft tubing airlift reactor ( Oksman-Caldentey, et al. , 2002 ) .
Figure 3: Pneumatically agitated reactors: ( a ) bubble column, ( B ) airlift reactor ( internal cringle ) , ( degree Celsius ) airlift reactor ( external cringle ) , and ( vitamin D ) airlift reactor ( draught tubing ) . A, air recess ; G, gas fumes. ( Oksman-Caldentey, et al. , 2002 )
Figure 4: Gas and liquid flow form Figure 5: Airlift bioreactor with external with internal cringle rhythm recirculation pump
AIRLIFT BIOREACTORS VERSUS CONVENTIONAL STIRRED TANK REACTORS
Gas-Liquid Mass Transportation
Merchuk, 1990, states that the volumetric mass transportation coefficient, KLa, is ‘the rate of gas transportation across the gas-liquid interface, per unit volume of the suspension and per unit of driving force. ‘
The volumetric mass transportation coefficient for external cringle airlift Fermenter is estimated as ( Najafpour, 2007 ) :
KLa & A ; lt ; 0.32ug0.7 ( 1 )
KL = Mass Transfer coefficient
a = Gas-liquid interfacial country per unit volume of the liquid
ug = Gas speed
The tallness of liquid in airlift reactors, hectoliter, have an consequence on KLa values as hectoliter strongly influences the circulation speed of the liquid and therefore the overall gas armed robbery ( Martens et al. , 1993 ) . The tallness of liquid can be every bit high as 60m in a big vas doing the resulting force per unit area to increase the O solubility and hence increasing the KLa value ( Najafpour, 2007 ) . The tallness of airlift reactors is typically approximately 10 times the diameter of the column ( H = 10D ) ( Najafpour, 2007 ) .
Due to the tallness and presence of a cringle in the ALR, high efficiency mass transportation was shown every bit good as betterments in both the flow and blending belongingss of the vas ( Vogel, 1997 ) .
Harmonizing to Malfait, 1981, an improved productiveness of the ALR as compared to a STR was seen and this is chiefly due to the higher overall mass transportation coefficient available in an ALR.
Of all foods supplied for aerophilic agitation, O is the lowest solubility and frequently is the restricting food ( Chisti, 1989 ) . Sufficient O should be supplied to fit the really rapid O ingestion by micro-organisms in order to keep the coveted productiveness ( Chisti, 1989 ) .
There is high gas-liquid contact country in ALRs every bit good as easy remotion or refilling of atoms, and high heat and mass transportation rates ( Tongwang, 2006 ) . In an ALR, there is superior O transportation public presentation ( See Fig. 6 ) and provides great productivenesss with barm, bacteriums and filiform Fungis as stated by Oldshue, 1983, and Martens et al. , 1993. Particularly in low viscousness media, ALRs are capable of presenting O at high transportation rates ( Merchuk, 1990 ) .
ALR aeration efficiency and public presentation are instead insensitive to alterations in operating conditions, doing ALR suited for procedures with altering O demands ( Merchuk, 1990 ) . However, a recent paper by Najafpour, 2007, claims that in an ALR nevertheless, as the micro-organism circulate through, the conditions change, and it is impossible to keep consistent degrees of C beginning, foods and oxygen through- out the vas.
In an STR, better O transportation is seen with the usage of scaremongers and baffles. It is possible to modify the rate of stirring to provide to greater flexibleness in covering with rheological alterations within the medium that can act upon O transportation and commixture ( Fontana et al. , 1999 ) .
Figure 6: Performance of ALRs and stirred armored combat vehicles versus O transportation rate. a, rectangular ALR ; B, split-cylinder ALR ; degree Celsiuss, agitated armored combat vehicle ; vitamin D, bubble column. ( Orazem and Erickson, 1979 )
Reactors must be able to hold effectual agitation and commixture capablenesss so as to obtain a homogeneous and unvarying distribution of foods and transferred O into the majority medium. This is to forestall the presence of dead zones and possible anoxia ( Chisti, 1989 ; Najafpour, 2007 ) . The hydrokineticss within the reactor may besides impact public presentation parametric quantities such as mass and heat transportation every bit good as strength of turbulency in the reactor ( Chisti, 1989 ) .
Properties of the fluids may perplex the commixture ability and O transportation ( Oolman and Blanch, 1986 ; Schugert, 1981 ) . Some bacterial and yeast agitation give rise to a extremely syrupy and non-Newtonian system ( Chisti, 1989 ) . With these non-newtonian media, sufficient commixture and mass transportation can non be provided by ALRs ( Doran, 2009 ) . STRs would be more suited for such syrupy fluids, although, mass-transfer rates decline really quickly with viscousnesss higher than 50-100 cP ( Doran 2009 ) . Multiple impellers can be installed in tall fermenters to better commixture ( Doran, 2009 ) .
The grade of shear that may be tolerated to accomplish sufficient O mass transportation is an extra restraint on the commixture and mass transportation in biological systems. Excessive rate can do harm to micro-organisms and interrupt the cell wall, whereas, low shear can do unwanted flocculation of cells, or even bacterial growing on the scaremonger and reactor walls ( Najafpour, 2007 ; Markl et al. , 1987 )
In STRs, there may be harm to the micro-organisms go throughing through the high shear zone of the impeller ( Vogel, 1997 ) . Possible harm to fragile cells from the ensuing shear forces and turbulency at the terminal of the scaremonger blades can avoided by utilizing an ALR ( Flickinger et al. , 1999 ) . The possible shear harm caused to cells in STR may be a factor to its hapless public presentation ( Markl et al. , 1987 ) .
ALRs are known to hold drastically lower degrees of shear as compared to STRs ( Oksman-Caldentey, et al. , 2002 ) . Due to its low shear, there is besides low commixture ; hence, the ALR can be used for turning delicate tissue, works and animate being cells ( Najafpour, 2007 ) . The flow government in an ALR depends on the sparger used and the flow rate ( Vogel, 1997 ) . Assorted types of spargers can be used to supply different bubble size ( Vogel, 1997 ) .
The degree of shear besides affects the microbic morphology in other ways ( e.g. whether a cast will turn as a mycelial mass or form pellets ) ( Chisti, 1989 ) . This pelletized growing can foster curtail O transportation ( Chisti, 1989 ) .
The allowable degrees of shear are predicted to be more rigorous in the hereafter due to increasing biotechnological progresss with future utilizations on plant/animal civilizations and genetically modified micro-organism which are less robust ( Humphrey, 1984 ; Schuler et al. , 1984 )
The presence of froth causes reduced efficiency in gas-liquid separation ( Najafpour, 2007 ) . Variations in biomass concentration, viscousness, surface tenseness and ionic concentration can do operational jobs such as foaming, flotation and bubble coalescency ( Oksman-Caldentey, et al. , 2002 ) .
Bubble coalescency frequently occurs in ALRs and should be minimized. If the provender enters the reactor at merely one location, the micro-organism will bring forth unwanted byproducts due to it sing uninterrupted rhythms of high growing and famishment. This would ensue in low outputs and high decease rates and therefore, multiple provender entries are used particularly on a big graduated table ( Najafpour, 2007 ) .
In an STR, equal headspace is provided by holding the volume filled 70-80 % with liquid so as to suit the presence of any froth, which may develop ( Doran, 2009 ) . To battle frothing farther, a auxiliary impeller called a froth ledgeman may be installed ( Doran, 2009 ) . Mechanical froth dispersion is by and large preferred as chemical antifoam agents causes decreased rates of O transportation ( Doran, 2009 ) .
Changeless temperature and heat transportation is required to obtain the coveted optimum microbic growing ( Najafpour, 2007 ) . More heat is generated from mechanical agitation than from sparging of compressed gas ( Doran, 2009 ) . This heat energy in the STR has to be removed to maintain the temperature invariable within the STR ( Chisti, 1989 ) doing temperature control for an STR more hard.
When the heat released is high, such as the production of individual cell proteins from methyl alcohol, it may be hard to take such high exothermal heat of reaction with a conventional stirred-tank design. Hence, ALRs may be the preferable pick ( Najafpour, 2007 ; Doran, 2009 )
A possible disadvantage of airlift engineering is that it may non be possible to accomplish cell growing every bit high as obtained in moved reactors on a regular basis ( Oksman-Caldentey, et al. , 2002 ) .
A survey done by Fontana, 2009, showed that the airlift had lower cellular growing as compared to an STR ( See Fig below ) . However, due to the close consequences, this suggests that the airlift has potency for usage in the production of the enzymes in big graduated table, with lower operating costs.
Figure 8: Time class of Aspergillus oryzae cultivation in WBEG medium in the airlift bioreactor. ( A ) Cell, cut downing sugar, and dissolved O concentration. ( B ) Endo- polygalacturonase ( endo-PG ) and exo-polygalacturonase ( exo-PG ) activities, and pH ( Fontana, 2009 )
Figure 7: Time class of Aspergillus oryzae cultivation in WBEG medium in the moved armored combat vehicle reactor. ( A ) Cell, cut downing sugar, and dissolved O concentration. ( B ) Endo- polygalacturonase ( endo-PG ) and exo-polygalacturonase ( exo-PG ) activities, and pH ( Fontana, 2009 )
ALRs supply lower power economic sciences as mechanical agitation would necessitate a high energy input per unit volume so as to keep the homogeneousness of the system and assistance O transportation ( Hess et al. , 2002 ; Wu et al. , 2002 ; Doran, 2009 ) . Mechanically agitated reactors are impracticable at volumes greater than approximately 500m3 as the power required to accomplish equal commixture becomes highly high ( Doran, 2009 ) .
Not merely ALRs are cheaper in footings of operating costs but besides with capital costs. The decreased capital cost is chiefly due to their simple mechanical design without the demand for an fomenter, gear box, and structural steel ( Chisti, 1989 ; Vogel, 1997 ) .
STRs require complex mechanical seals to forestall taint by unwanted microbic species ( Chisti, 1989 ) . Due to this complexness, STRs are therefore more expensive and less robust than other bioreactors ( Vogel, 1997 ) .
Harmonizing to Najafpour, 2007, nevertheless, though the ALRs may be cheaper due the fact that an fomenter is non needed, but a larger air throughput is required and the air besides has to be at a higher force per unit area, particularly on large-scale. Vogel, 1997, suggests the usage of air compressors to cut down power costs. These air compressors can be driven by steam and allows continued operation during power outages in big workss with minimum power coevals control.
Further betterments can be made to acquire better energy economic system by utilizing a 2nd sparger in the top portion of the downcomer ( Merchuk, 1990 ) . By increasing the liquid speed, so the free lifting speed of the bubbles is generated, doing the gas to be carried down, hence a longer gas-liquid contact clip ( Merchuk, 1990 ) . This will so decrease the energy demands as some of the gas is injected against a much lower hydrostatic force per unit area ( Merchuk, 1990 ) .
Asepsis is hard to keep for long periods in an STR particularly in uninterrupted operations and where the impeller shaft must be necessarily base on balls into the vas ( Najafpour, 2007 )
In an ALR, asepsis is easy maintained, as there is less danger of taint through seals of mechanical fomenters ( Siegel et al. , 1992 ; Najafpour, 2007 ) . Furthermore, there is besides a lower chance of mechanical failure in an ALR ( Flickinger, et al. , 1999 ) . No care of motors, gear boxs, seals and bearings are required in ALRs ( Vogel, 1997 ) . Due to the perpendicular orientation and deficiency of internals in ALRs, easier cleansing and sterilisation can be maintained ( Siegel et al. , 1992 ) .
Construction and Design Flexibility
ALRs are have really simple building design leting the possibility of building larger fermenters as the design is non limited by motor size, weight and shaft length as seen with STRs ( Vogel, 1997 ; Siegel et al. , 1992 )
The ALR lack the flexibleness as compared to STR as their design requires being more exact. Factors such as the geometry of the system has to be carefully defined as it can impact the circulation rates, the commixture clip, and the volumetric mass transportation coefficient ( Gavrilescu and Tudose, 1998 ) .
Harmonizing to Siegel, 1992, there has been really few informations on ALR conveyance phenomena during the existent agitation. A bulk of the surveies carried out on ALRs are on the growing dynamicss during the agitation procedure alternatively. These surveies have been conducted on little bench-scale ALRs due to be limitations and complexnesss involved in large-scale surveies. The bench-scale surveies do non supply the basic hydrodynamic and mass transportation information necessity for successful ALR scale-up.
Due to this deficiency of informations, biochemical industries hesitate in utilizing ALRs for commercial application. The STRs are still widely favored due to its ‘off-the-shelf ‘ convenience and chiseled public presentation and scale-up belongingss. Reports of improved public presentation by ALRs on the bench-scale is non plenty to convert the biochemical industry in extensively utilizing the ALRs due to uncertainties of its public presentation after scale-up ( Siegel et al. , 1992 ) .
The restrictions of STRs have led to the development of other bioreactors such as pneumatically driven bioreactors such as ALRs. The ALRs are seen to hold the greatest potency with the possibility of supplying the aeration and agitation with a low energy input. Particular involvement is being focused on the usage of ALR with tissue civilizations due to its shear sensitiveness, clemency and uniformity of turbulency.
The ALR has excellent contact among stages, foods are easy replenished and has high heat and mass transportation rates. There is easier temperature control in ALRs as compared to STRs.
While the ALR seems to be the better pick, biochemical industries still hesitate in utilizing ALRs due to the deficiency of information and low adulthood of the bioreactor.