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过滤技术原理及应用质保处2009.05主要内容•过滤知识及原理•过滤器的使用及维护•完整性测试•自动完整性测试仪IntroductiontoFiltration过滤基本知识主要内容•ImportantdifferencesinthetypesoffiltersusedinBioprocesses.•–生物制药中使用的不同类型过滤器及其特性•Whyweusemembranefiltersforcriticalapplication•–关键应用中为什么使用膜过滤器主要内容—续•Howtorecognizefiltrationproblemsandperformbasictroubleshooting•–怎样理解过滤中的问题和解决简单故障什么是过滤？HowdoFiltersWork?过滤机理•SizeExclusion大小排除–Particlesaretoolargetopassthroughthe“pore”–基于大小来分离–Examplesaretermedentrapment,sieving,surfacecapture–例如拦截,筛分,表面捕获•Adsorption吸附–Particlessticktothefilterbychemical/electricalattraction–颗粒由于化学/电荷作用粘附在滤器上RetentionMechanisms影响过滤的因素•Mechanismscanbeaffectedby:•截流机制可以被以下因素影响：–Fluidcharacteristics–流体特性–Operatingconditions–操作条件–Particletype–颗粒类型–Filtertype–过滤膜类型影响过滤的因素(流体特性)•Viscosity粘度•Chemical/Ioniccontent•化学/离子成分•Comments–Slowflowallowsmorecontact较慢流速有较多接触–Mixing/Contacttimecanbecritical混合/接触时间有较大影响•Onlyaffectadsorptiveretention•只影响吸附截留•-NOTsizeexclusion•不影响大小排除影响过滤的因素(操作条件)•Particlespeed/velocity颗粒速度•Appliedpressure过滤压力•Comments建议–Slowflowisgood选择低流速–betterretentionatslowerflow越低的流速,越好的截留–Matrixmovementisbad结构移动是不利的–particlesandfiberscanbereleasedfromdepthfilters–颗粒和纤维能从深层过滤器析出•Velocity/DifferentialPressurecanhaveamajoreffectonadsorptiveretention-Littletonoeffectonsizeexclusion速度/压差对吸附截留有重要影响,对大小排除影响相当小影响过滤的因素(颗粒类型)•Deformable(soft)可变形颗粒–Non-deformable(hard)不可变形颗粒•Comments建议–Underpressuresoftparticlescanintrudeintothefilterstructurecausingmoreeffectivefilterblinding–在压力下软性颗粒会进入过滤膜内并导致更多的过滤堵塞–例如:凝胶–Hardparticlesformopencakes–硬颗粒形成一层饼例如:沙子影响过滤的因素(滤膜的影响)•Porerating孔径•Structure结构–Rigidormovable刚性或可移动•Comments–Sterilizingfilter–commonrating(legaldefinition)除菌过滤-公共孔径(法规定义)–Prefiltershavenominalratings-eachmanufacturerhastheirownstandardsandmethods–预过滤---额定孔径,每一个制造商有自己的定义和方法0.22umDuraporeSurface(3,000x)0.22umDuraporeCross-section(600x)FilterMaterials–Hydrophilic过滤材质—亲水性•“WaterLoving”亲水–Wetspontaneously(orwithlittleeffort)withwater»Cellulosicmaterials(i.e.Regeneratedcellulose,mixedcelluloseester,etc.)纤维素材料»Polycarbonatewithadditives(i.e.PVPP),Modifiedpolysulfone,Nylon,Modifiedpolyvinylidenefluoride(PVDF)聚碳化合物•Applications应用–Filtrationandsterilefiltrationofaqueousoraqueous/organicsolutions水或水/有机溶液混合的过滤和除菌过滤FilterMaterialsHydrophobic过滤材质—疏水性•“Waterhating”疏水–Notspontaneouslywetwithwater.–Watercanremainorbe“tricked”toenterfilter水被截流或巧妙进入膜–PTFE-Polytetrafluoroethylene,PVDF-PolyvinylidenefluoridePolypropylene,Polysulfone,Polycarbonate•Applications应用–Solvent,acid,base,and–chemicalfiltration溶剂,酸,碱和化学品过滤–Tank/Equipmentvents,processgas,fermentationinlet/exhaustfilters–罐/设备呼吸器,工艺用气,发酵进气/排气过滤过滤器分类•深层过滤器•表面过滤器特性•膜过滤器WhatdoDepthFilterslooklike?深层过滤器•Fibrous(canshedfibers)纤维(有纤维脱落)•Difficulttogiveanaccurateporesizerating不能给出一个确切的空径•Thick(3-30mm)&oftenadsorptive厚度(3-30毫米),通常有吸附•Giveapercentage(i.e.30-70%)particlereduction只能给出颗粒减少的比例•Havethegreatestcapacity较大的承污能力•Examples-Microfiberglass,String-wound,padfilters例如-玻璃纤维,线绕式,压板式WhatdoSurfaceFilterslooklike?表面过滤器•Fiberslockedtogetherbyheatormembranecoating纤维用热粘合或膜涂布•Givenanominalratingorratedbythefilteritprotects可以给出公称空径•Thin(1mmorless)&SlightlyAdsorptive较薄(小于1毫米),较小吸附•Giveapercentage(90-99.9%)particlereduction给出颗粒减少的比例(90-99.9%)•Examples-Celluloseestercoatedcelluloseorpolyesterweb例如-纤维素酯涂纤维或聚酯片KeyMembraneFilterCharacteristics膜过滤器的特性•Strong,RigidNOTbrittle坚强，硬不易碎•Tortuouspathway曲折的通道•Notalltheretentionontop•不是都截流在膜表面•Veryhighinternalarea•非常高的内表面积•65-75%porosity•65%-75%开孔率KeyMembraneFilterCharacteristics膜过滤器的特性-续•Sizeexclusion–particleretentiondoesnotchangewithfloworpressure•大小排除－颗粒截流与流速和压力无关•Sterilizingfiltersmusthave99.99999%removal•无菌过滤器必须具有大于99.99999%截流•Integritytestable(diffusion&/orbubblepoint)•能做完整性测试HowareMembraneFiltersMade?膜过滤是怎样制造的？•ProducedbyCasting•铸造膜–Nylon,Cellulose(mixed–ester,regenerated),PVDF,Polysulfone–尼龙,纤维素(混合酯,改良),聚偏二氟乙烯,聚砜•ProducedbyStretching•拉伸膜–PTFE–聚四氟乙烯WhatdoCastFilterslooklike?铸造方式制造的膜过滤器•Mainlymadebycastingmembrane•主要由铸造方式制造•Canbeeitherhydrophilicor•hydrophobic•可以是亲水和疏水•Ratedonthesizeofthesmallestparticle•itretains•孔径是对最小的颗粒的截留•Verythin(100-260um)•非常薄（100-260微米）•Adsorptiondependsonmaterials•吸附与材料相关•Examples例如•Celluloseester纤维素酯•Regeneratedcellulose改良纤维素•Nylon尼龙•Polysulfones聚砜•PVDF聚偏二氟乙烯WhatdoStretchedfilterslooklike?拉伸方式制造的膜过滤器•Slotshapedpores•狭窄的孔道•Verythin•非常薄•Oftenbondedtoasupport•material•常常与支撑结合•Canhavehighprotein•adsorption•有较高的蛋白吸附•Examples例如•PTFE-Teflon聚四氟乙烯•Naturallyhydrophobic天然疏水•Mosthydrophobicpolymer过滤系统配置澄清(Millistak+orPolygard)预过滤(MilligardorPolysep-II)最终(Durapore0.22or0.45μm）深层表面膜过滤系统配置•–孔径逐渐减小的过滤系列•–Clarifyingfilter-澄清过滤–•深层过滤–•在过滤系列开始是最大的–过滤容量•–Prefilter-预过滤–•Prefilter-预过滤-表面过滤–•中等截留，中等载量•–Finalfilter-除菌过滤–•除菌膜–•最大的过滤截留率PerformanceofFiltrationSystems过滤系统性能TypesofParticlesinBiologicalFluids生物流体中颗粒类型•Non-deformabletypes•不可变形颗粒–Resinbeadsorfines树脂粒–Drugcrystals药物晶体–Carbonfines炭粒–DiatomaceousEarth(D.E.)硅燥土–Formporouspermeablecakes.在膜上形成可流通的饼•Deformabletypes•可变形颗粒–Proteins蛋白–Lipids脂•Sugarcomplexes糖复合物Canmoveth