Reactor Engineering in Large Scale Animal Cell Culture

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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.Theseinteractionsaredifficulttore-suspensioncultureinagitatedbioreactorssolvebutifhigherspargeandagitationintensities>10,000Lbecausetheyhavebecomethesystemcouldbeusedtoachievethenecessaryoxygenof

3、choiceindustrially.Itisparticularlyconcernedtransfer,theproblemwouldlargelydisappear.withproblemsthatbecomeincreasinglyimpor-Thus,theperceptionofshearsensitivityisstilltantasthescaleincreases.However,veryfewimpactingonthedevelopmentofanimalcellpapershavebeenwrittenthatareactuallybasedcultu

4、reatthecommercialscale.Microcarrieronsuchlarge-scalestudiesandthefewthatdocultureisalsobrieflyaddressed.Finally,somerarelyaddressanyoftheissuesquantitatively.recommendationsforbioreactorconfigurationHence,itisnecessaryveryoftentoextrapolateandoperatingstrategyaregiven.fromsmall-scaleworkandt

5、hisreviewtriestopullthetwotypesofstudytogether.ItisshownthatKeywordsLarge-scalebioreactorsÆShearshearsensitivityduetoagitationandburstingsensitivityÆHomogeneityÆpHcontrolÆbubblesisnolongerconsideredamajorproblem.DissolvedCO2ÆOsmolalityHomogeneitybecomesincreasinglyimportantwithrespecttopHa

6、ndnutrientsatthelargestscaleandsub-surfacefeedingisrecommendedIntroductiondespitecleaninginplaceconcerns.Therearestillmajorquestionswithcellretention/recycleProbablythefirstdescriptionofanagitated,systemsatthesescales,eitherbecauseoffouling,stainlesssteelanimalcellculturebioreactorwasofcapa

7、cityorofpotentialanddifferentshearoneof30Lfortheproductionofinactivatedfootsensitivityquestions.Fed-batchoperationgivesandmouthdiseasevaccinefromfreelysuspendedrisetocelldensitiesthathaveledtotheuseofBHKcells(TellingandElsworth1965);andfromoxygenandenrichedair