4 Process Involved in Scale up Criteria | Microbial BioprocessingAdvertisements:(1) Microbial Cell Process:Theoretically the following criteria were assumed suitable basis for scale up of bioreactors! Constant power input per unit volume "P#$ % constant&B Constant '(aC Constant mi)ing *uality+ Constant momentum factor "M, % -+ -.( "+ / .&& % constant&0 Similar drop si1e distribution "ds % constant&, Constant impeller tip speed "2 -+i % constant&3 Constant mi)ing rate number % "-#'&"+i#+t&4 constantShort accounts of scaling up of bioreactors of fermenters on the basis of these criteria are discussed below51. Constant power input per unit volume:,or scaling up based on these criteria it is necessary to consider whether it is gassed or non6gassed system ,rom the wor7 of 8ushton and his associates9 for geometrically similar9 fully baffled vessels with turbulent conditions9 it may be noted that ifscale up should be based on maintaining a constant power input per unit volume considering no gassing in the system one may have the following(i) Non-gassed Sstem:.hen there is no gassing in the system then based on constant P#$ has the power number9 -p asIt was also apparent that in an oil drop dispersion system ds could serve as important criteria for scale up The value of :a; in e*uation ? whereas for draft tube fermented its value ranges between 6>@A to 6>=A!. Constant impeller tip speed:It was rather surprising to recogni1e that most of the data on impeller tip speeds collected were in the range A6B m sec6 @indicating the predominant importance of this parameter in scale up Specially in antibiotic production plants constancy in tip speed "2 -+i& was encountered in several cases ,or scale upIn e*uation "4& the following correlations will be applicable depending on the type of mi)er used,or turbine impeller mi)er(() Scale )p o% *ilamentous Cell *ermentation:!erobic fermentative bioprocessing using filamentous microorganisms cover a wide range of industrially important bio6product formation systems $arious Streptomyces sp antibiotic fermentations fall in this group Such bioprocessing e)hibit viscous and non -ewtonian behavior following Power law fluid charactersThese processes are typical and present considerable problems in mi)ing and mass transfer for scale up purpose Thus9 agitatorpower number "-P& and impeller diameter "+i& are important case factors towards implications of Power law fluid on scale upalong with li*uid volume "$(& and "D( #+t& ratioCase 1:!gitator power "Pt& number influencea Provided with same geometry9 vs9 "Pt#$t&9 $( and +i manipulation of volumetric mass transfer e*uations show(+) Mammalian Cell Processing Scale )p:In scaling up bioreactors of mammalian cell bioprocess most of the correlations are based on laboratory models alone and still awaits confirmation of their utility in industrial production concern ,or mammalian cell bioprocessing current industrial scales typically involve bul7 li*uid volume of FA# per day per bioreactor for continuous or semi6continuous systemsIn batch processing this bioreactor volume ranges between A>>6A>>> I capacities9 operating over @6= wee7s There are no established scales up criteria for scaling up mammalian cell culture process Cell culture engineers therefore9 still largely depend on concepts and scale up procedures developed for chemical or microbial#biochemical processes to begin withDowever9 an engineering body of e)perience and data will increasingly enable more specific design engineering and scale up procedures for mammalian cell culture bioprocesses in which 7inetics is li7ely to be influenced by many factors and associated with many problems and limitationsIn scaling up procedures specific to animal cell culture9 effect ofscale on o)ygen mass transfer through micro6porous membranes li7e silicone tubes for supplying bubble free o)ygenation has been investigated In order to aerate cell cultures9 the membrane is immersed in the medium and the gasmi)ture "eg air9 CJF and JF& is passed through the tube under pressure+epending on the difference in pressure between the gas and the medium9 gas flows through the membrane tube Bubble freeaeration is achieved if the internal gas pressure does not e)ceed the pressure at which bubbles will form Correlation for bubble free o)ygenation through membrane tubes has been developed,or this9 novel bioreactors have been designed for cell culture engineering in large *uantities of the fragile comple) mammalian cells that synthesi1e commercially and medically important proteins such as interferon and monoclonal antibodies The correlation for bubble free o)ygen using silicone micro6porous tube for o)ygen mass transfer in this novel bioreactor has been given by the following correlationsIn these correlations9 Sh is Sherwood number9 ' is film mass transfer coefficient "m sK@ &9 d is tube diameters9 +> is molecular diffusivity of o)ygen "mF s6@&9 e9 f9 g are specific constants9 +t is bioreactor diameter "m& and -8e is impeller 8eynolds numberThe provision of an ade*uate o)ygen supply to large volumes of mammalian cells is the most crucial barrier to scale up9 especially in suspension systems J)ygen is only sparingly solube in cell culture medium ">F m mole JFI6@& J)ygen demand of a culture "@>? cells per ml& ranges between >>A= m mole JF l6@ h6@ and >AL m mole JFI6@ h6@ depending on the type of cell Scale up of mammalian cell cultures are9 therefore9 bound by several barriers as shown in Table 9 -8e and +t are given and e9 f and g are determined e)perimentally9 then e*uation NRe > 07!777. (or a pitched-blade turbine the power number! which remains constant in the turbulent range! will begin to increase in the transition and viscous regime. (or simplicity! let?s assume that the power number does not begin to increase until the /eynolds number drops below =77. @ad the /eynolds number been less than =77! we would have to make an appropriate correction to the power number and use that corrected number to calculate power and tor"ue characteristics of the mixer. #his additional step to correct power number should be done for each subse"uent step in the scale-up process if the /eynolds number suggests that such a correction is necessary. (9ower number corrections differ with type of impeller.)Aow suppose we want to duplicate our process results in an 84.7 in.-dia. tank with a 3!777 gal capacity using four-blade! pitched-blade turbines. As we will see while doing the calculations! the tank geometry and impeller type both change in the scale-up process. Suchchanges are common. 6n this particular case! a combination of experience! literature research and experimentation leads us to believe that the tip speed should be held constant when we scale-up and that tor"ue-per-volume may represent mixing intensity.As a first step in our scale-up calculation! we will use geometrical similarity to do a scale-up from our )).5 in.-dia. pilot tank to an 84-in.-dia. process tank. Geometric similarity means that our scale-up length ratio of 84;)).5 : B.3 will multiply all of the length dimensions. #hus! the 5.7 in.-dia. pilot turbine will scale-up to a 3C.5 in.-dia turbine in the large-scale tank and the li"uid level will be B.3 D )).)0 : 8).0 inches. @owever! this li"uid level provides a volumeof only )!=48 gal. e will need to ad'ust the li"uid level later to get our desired results.#o maintain the same tip speed in the large-scale mixer as in the pilot unit! we must ad'ust rotational speed because the impeller diameters differ and impeller diameter times rotational speed gives tip speed. So! for e"ual tip speed! the operating speed for the large-scale mixer is&377 ()).5;84) : 4).) rpmAt 4).) rpm! we can do the same calculations we did for the pilot-scale results.As shown in the table! geometric scale-up with constant tip speed increased the /eynolds number! power and tor"ue. @owever! power per volume decreased and tor"ue per volume remained constant. (or this first step in our scale-up process! both tip speed and tor"ue per volume remained constant! which satisfies our process scale-up ob'ectives.The next stepAt this point we will change to the four-blade turbines re"uired in our large-scale process. #he four-blade turbines have a power number of ).3B instead of ).)=E so we can round downthe turbine diameter to 3C.7 in. and round up the speed to 40.7 rpm. Such ad'ustments seemboth reasonable and practical. @owever! we should recalculate our mixing results to be sure.ith this turbine change! tip speed essentially stays constant and our tor"ue per volume rises by a little more than 07