高效分离纯化工艺-面对发酵行业对化学品消耗及收课件

EfficientDemineralization–AChallengeForFermentationProducts1EfficientPurification–AChallengeForFermentationProducts高效分离纯化工艺-面对发酵行业对化学品消耗及收率的挑战November20122012年11月NovasepProcess:YourPurificationSpecialistforBio-Industries2关于诺华赛

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NOVASEP2010营业额:3亿欧元

(4.18亿美元)1200员工,其中研发人员超过200人2010revenues:300M€(USD418M)

1200employees,200inR&D每年超过100个研发项目每年生产超过1000个活性分子全球有2000余套分离纯化系统Over100R&DprojectsperyearOver100activemoleculesproducedperyearOver2,000purificationsystemsinstalledworldwideNovasepProcess:YourPurificationSpecialistforBio-Industries3间歇色谱CHROMATO.蒸发精馏EVAPO.离子交换IEX膜过滤MF分离纯化PURIFICATION结晶CRYSTALIZATION连续色谱SSMB诺华赛：全程分离纯化方案提供者

Novasep:PurificationSolutionProvider纯度Purity原料制备化学合成和生物制造BIOMANUFACTURING发酵细胞培养危险化学品手性化学品

高能化合物电渗析ED4ProducingbyFermentation挑战-发酵产品的分离纯化PureProduct纯净产品EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战5Purificationisoftennoteconomical!纯化过程常常不经济PureProduct纯净产品EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战BatchIEXDemineralization间歇式离交脱盐Crystallization结晶HighEffluentGeneration产生大量废水HighChemicalsConsumption高化学品消耗MotherLiquor母液LowvalueOutcome低价值品6Howtoimproveyoureconomics?如何提高经济性?PureProduct纯净产品EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战BatchIEXDemineralizationCrystallizationHighEffluentGeneration产生大量废水HighChemicalsConsumption高化学品消耗MotherLiquor母液LowvalueOutcome低价值附产品ReduceThese!减少这些!IncreaseThis!提高这个!ReducingChemicalsConsumption

减少化学品消耗

EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战7ReducingChemicalsConsumption

减少化学品消耗Selecttherighttechnology,accordingtoyourlocalconditions!!!根据实际工艺状况,选择正确的脱盐技术BatchIEX间歇离交:

lowsaltloads低含盐量ContinuousIEX连续离交: mediumtohighsaltloads中--高含盐量Electrodialysis电渗析: mediumtohighsaltloads,whenelectricityischeap中--高含盐量,且电较便宜SSMBChromatography色谱: hightoveryhighsaltloads高--极高含盐量Whenusingaresinbasedtechnology,selectthemostadaptedresin,onacasetocasebasis!当采用基于树脂的技术时,需要基于特定的工艺环境,选择合适的树脂工艺：Novasephas200+referencesofresinsinportfolio!诺华赛已有200个以上个成功运用树脂的工程案例EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战8DifferentProcessRoutesforOrganicAcids

针对有机酸的不同工艺路线EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战9Lysinepurification

案例：赖氨酸连续离交纯化

CONTINUOUS(limitedbuffertanks)生产连续(缓冲罐减小)Feedandtreatedproduct进料罐和处理后产品罐Chemicalsandwaste化学品储罐和废水罐ReuseWatersystem重用水系统BETTERUTILITIESUSAGE公用工程的更好利用Lesschemicals更低的化学品消耗Lesswater更少的水耗Lesseffluents更少的废水量LESSDILUTIONDURINGDISPLACEMENT(productorreagent)STEPS置换环节减少稀释(生产或再生)Morestableandhighoutletproductconcentration更稳定更高的产品浓度Lesswatertoevaporate更少的蒸发水量CONTINUOUSPROCESSADVANTAGES连续处理工艺的优势ContinuousIonExchangevsDiscontinuous

Principle&Advantages连续离交与非连续离交的对比CONTINUOUSPROCESSLIMITATIONS:连续处理工艺的局限

Maxlinearvelocityforproperadsorption/Elution吸附/洗脱时需要更大的线速度Pressuredropconsiderations要注意压力降因素TypicalMassbalance1System/1PeriodContinuousIonExchangeappliedtolysinepurification连续离子交换在赖氨酸纯化中的应用KeyFigures

主要数据KeyPerformancesFiguresforContinuousIonExchangeonLysinepurification赖氨酸纯化连续离交系统的主要性能参数*:Withouttakingintoaccountbackwashingsequence:0,75BV/period.Dependingonpressuredropandsuspendedsolids没有计入反洗水消耗：约0.75BV/周期，根据压力降及悬浮物变化

ResinLoading树脂负载量180gLys/literresin-MinimumRecovery收率98.5%-MinimumLysineConcentrationinRC

赖氨酸浓度195gLys/L

+/-15g/LLysinecaptureduringadsorption吸附环节赖氨酸捕获率99%Waterconsumption*水耗1,8BV/PeriodH2SO498%consumption98%浓度硫酸消耗<4%Mass/VolumeFeed(i.e.40kg/m3feed)NH3Consumption氨水消耗35gNH3100%/LregeneratedresinNOVASEPSYSTEMFORLYSINE:11CELLSCONTINUOUSPROCESS+1CELLINSPARE

诺华赛设计的赖氨酸生产系统：11个连续工艺单元+

1个备用单元ContinuousIonExchangeNovasepdesign赖氨酸连续离交工业装置15

ADVANTAGES

基于SSMB连续离交的设计优点MECHANICALDESIGN机械设计NOMOVINGPARTS/STATICCOLUMNS无移动部件COMPACTINLET/OUTLETMULTIPLEPORTVALVESONEACHCOLUMN通过高度紧凑的多通道自控阀门切换物料MAINTENANCECAPABILITIES/REQUIREMENTS维修维护POSSIBILITYTOHAVEONECOLUMNOFFCYCLEWITHOUTSTOPPINGTHEPLANTFORGENERALMAINTENANCE,RESINREPLACEMENT…可以在不终正生产的情况下，将任意一个需要柱子单独隔离出来进行维护、树脂更换…LESSMAINTENANCEREQUIREMENTS,SIMILARTODISCONTINUOUSPROCESS

更少的维护要求，在维护上与间歇工艺相似16PROCESSCONTROL

工艺控制POSSIBILITYWITHOUTANYPIPINGMODIFICATIONTOADJUSTPROCESSZONES(SOFTWAREMODIFICATIONSONLY).能够在不进行任何管道物理连接的情况下，对各个柱子的工艺区进行调整（只是对自控软件进行设置）.POSSIBILITYTOPRECISELYMETERALLFLOWSONEACHCOLUMN,FOREACHPROCESSSTEP.

能够非常精确的对流经每一根离交柱/每一个子步骤的流量进行调整.4）EXCELLENTDISTRIBUTORSDESIGN卓越的分布器设计

Excellentdistributorsquality(Chromatographygrade)–whichguaranteedthebestflowdistributions，andnoresinleakages.色谱分离级别的分布器，保证无比均匀的流体分布，杜绝树脂粉末逃逸现象；.

ADVANTAGES

基于SSMB连续离交的设计优点175）EASYPLANTEXPANSIONCAPABILITIES产能扩增的灵活性INCREMENTALINCREASEOFPLANTCAPACITYBYADDINGADDITIONALCOLUMNSANDADJUSTPROCESSZONESONTHEWHOLESETOFCOLUMNS在对系统产能进行扩增时，只需要额外增加离交柱，并对工艺软件进行重新设置即可；6）FOOTPRINT占地要求的灵活性MOREFOOTPRINTFLEXIBILITY可以根据客户现场空间的位置进行调整

ADVANTAGES

基于SSMB连续离交的设计优点EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战18SuccinicAcidPurification

案例：丁二酸纯化Succinicacidisakeychemicalintermediate丁二酸（琥珀酸）是一种重要的化学中间体Customer客户:

JVARD–BioAmberProcessdevelopmentworkstartedin2004工艺开发工作始于2004年TechnologyScreening技术筛选ProcessSimulation工艺模拟Processintegration工艺整合Pilotingwork试验工作1stindustrialBioSuccinicAcidplantworldwidestartedin2009,withCapacity3,000t/year全球第一个发酵法丁二酸工厂于2009年投产，产能为3000吨/年Otherstudieson-going(morethan6routesstudied)

另外的研发在继续中（超过6条研发路线）EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战19SuccinicAcidPurification

丁二酸的纯化ClarificationbyKerasep®membranefiltration用Kerasep®

陶瓷膜澄清过滤2differentprocesses,

dependingonlocalconditions:两套工艺路线（根据现场条件）Applexion®CIEX

连续离交工艺Novasep–Mega®Electrodialysis

电渗析工艺IMPROVEYOURREVENUEFROMMOTHERLIQUOR

从母液中提升收益

EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战20ImproveyourrevenuefromtheMotherLiquor

从母液中寻找收益Becauseofsolubilityequilibrium,MLiscontainingahighamountofyourmainhighvalueproduct!由于维持溶解平衡的原因，致使母液中含有大量高价值的产品ByusingSSMBChromatography,youcanseparatetheimpuritiesfromthevalueproduct,andrecovertheproduct!通过使用连续模拟移动床色谱工艺，可以将杂质与高品质产品分开，提高产品收率。Examples例如CitricacidML:recoveryincreaseupto98,5%,withpurity98%柠檬酸母液：收率上升至98.5%，纯度为98%EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战21Membranefiltrationtoclarifybroth陶瓷膜过滤澄清液体Concentration

浓缩Crystallization结晶Centrifugestoseparatecrystals离心分离MLChromatographytoseparatethreoninfromremainingnonfermentedsugars,andorganicandmineralimpurities采用色谱技术分离有机物及其它杂质ThreoninML:recoveryincreasefrom80%to95%+苏氨酸全程收率：从80%提升至95%以上.ThreoninMotherLiquorPurification案例：苏氨酸母液纯化EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战22Primaryfiltrationtoremovemycelium初级过滤去除菌丝体Membranefiltrationtoclarifybroth陶瓷膜过滤澄清液体Concentration浓缩Chromatographytoseparatecitricacidfromremainingnonfermentedsugars,andorganicandmineralimpurities采用色谱技术分离柠檬酸及其它杂质Polishingbyactivatedcarbonandionexchange活性炭和离子交换精制Evaporation蒸发Crystallization结晶CitricAcid–Gypsumfreeprocess

案例：柠檬酸无石膏生产工艺

EfficientDemineralization–AChallengeForFermentationProducts高效脱盐—针对发酵产品的挑战23Lesschemicals较少的化学品消耗Doesnotuselime不使用石灰;a