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1、Cytotechnology(2006)50:933DOI10.1007/s10616-006-9005-8ORIGINALPAPERReactorengineeringinlargescaleanimalcellcultureAlvinW.NienowReceived:29March2006/Accepted:29March2006/Publishedonline:Publishedonline:20June2006óSpringerScience+BusinessMediaB.V.2006AbstractThisarticlemainlyaddressestheissu
2、estionratethatimpactsonpHcontrol,pCO2andassociatedwiththeengineeringoflarge-scalefreeosmolality.Theseinteractionsaredif?culttore-suspensioncultureinagitatedbioreactorssolvebutifhigherspargeandagitationintensities>10,000Lbecausetheyhavebecomethesystemcouldbeusedtoachievethenecessaryoxygenof
3、choiceindustrially.Itisparticularlyconcernedtransfer,theproblemwouldlargelydisappear.withproblemsthatbecomeincreasinglyimpor-Thus,theperceptionofshearsensitivityisstilltantasthescaleincreases.However,veryfewimpactingonthedevelopmentofanimalcellpapershavebeenwrittenthatareactuallybasedcultu
4、reatthecommercialscale.Microcarrieronsuchlarge-scalestudiesandthefewthatdocultureisalsobrie?yaddressed.Finally,somerarelyaddressanyoftheissuesquantitatively.recommendationsforbioreactorcon?gurationHence,itisnecessaryveryoftentoextrapolateandoperatingstrategyaregiven.fromsmall-scaleworkandt
5、hisreviewtriestopullthetwotypesofstudytogether.ItisshownthatKeywordsLarge-scalebioreactors?Shearshearsensitivityduetoagitationandburstingsensitivity?Homogeneity?pHcontrol?bubblesisnolongerconsideredamajorproblem.DissolvedCO2?OsmolalityHomogeneitybecomesincreasinglyimportantwithrespecttopHa
6、ndnutrientsatthelargestscaleandsub-surfacefeedingisrecommendedIntroductiondespitecleaninginplaceconcerns.Therearestillmajorquestionswithcellretention/recycleProbablythe?rstdescriptionofanagitated,systemsatthesescales,eitherbecauseoffouling,stainlesssteelanimalcellculturebioreactorwasofcapa
7、cityorofpotentialanddifferentshearoneof30Lfortheproductionofinactivatedfootsensitivityquestions.Fed-batchoperationgivesandmouthdiseasevaccinefromfreelysuspendedrisetocelldensitiesthathaveledtotheuseofBHKcells(TellingandElsworth1965);andfromoxygenandenrichedair
