过滤器原理及优化

默克密理博高智群[e-mail]ion过滤知识及基本原理0.22µm123453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Howtorecognizefiltrationproblemsandperformbasictroubleshooting怎样理解过滤中的问题和解决简单故障4什么是过滤？5HowdoFiltersWork?过滤机理SizeExclusion大小排除Particlesaretoolargetopassthroughthepore”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6RetentionMechanisms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7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8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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9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10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)11FilterMaterials–Hydrophilic过滤材质—亲水性“WaterLoving”亲水Wetspontaneously(orwithlittleeffort)withwater水可浸润的Cellulosicmaterials(i.e.Regeneratedcellulose,mixedcelluloseester,etc.)纤维素材料(再生纤维素,混合纤维素酯Polycarbonatewithadditives(i.e.PVPP),聚碳酸酯,Modifiedpolysulfone改良聚乙烯,Nylon尼龙,Modifiedpolyvinylidenefluoride(PVDF)改良聚偏二氟乙烯Applications应用Filtrationandsterilefiltrationofaqueousoraqueous/organicsolutions水或水/有机溶液混合的过滤和除菌过滤12FilterMaterials–Hydrophobic过滤材质—疏水性“Waterhating”疏水Notspontaneouslywetwithwater.水不浸润Watercanremainorbe“tricked”toenterfilter水被截流或”引导”进入膜PTFE-Polytetrafluoroethylene,聚四氟,PVDF-Polyvinylidenefluoride聚偏二氟乙烯Polypropylene聚丙烯,Polysulfone聚砜,Polycarbonate聚碳酸酯Applications应用Solvent,acid,base,andchemicalfiltration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FilterStructure过滤器结构14WhatdoDepthFilterslooklike?深层过滤器Fibrous(canshedfibers)纤维(有纤维脱落)Difficulttogiveanaccurateporesizerating不能给出一个确切的孔径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15WhatdoSurfaceFilterslooklike?表面过滤器Fiberslockedtogetherbyheatormembranecoating纤维用热粘合或膜涂布Givenanominalratingorratedbythefilteritprotects可以给出额定孔径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16KeyMembraneFilterCharacteristics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%porosity65%-75%开孔率Sizeexclusion–particlebretentiondoesnotchangewithfloworpressure大小排除－颗粒截流与流速和压力无关Sterilizingfiltersmusthave99.99999%removalandsterilefiltrate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17HowareMembraneFiltersMade?膜过滤是怎样制造的？ProducedbyCasting铸造膜Nylon,Cellulose(mixedester,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MIXINGTHICKNESSCONTROLMEMBRANECASTINGHYDROPHILISATIONDRYINGENVIRONMENTALYCONTROLLEDCHAMBER3:1118WhatdoCastFilterslooklike?铸造方式制造的膜过滤器Mainlymadebycastingmembrane主要由铸造方式制造Canbeeitherhydrophilicorhydrophobic可以是亲水和疏水Ratedonthesizeofthesmallestparticleitretains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19WhatdoStretchedfilterslooklike?拉伸方式制造的膜过滤器Slotshapedpores狭窄的孔道Verythin非常薄Oftenbondedtoasupportmaterial常常与支撑结合Canhavehighproteinadsorption有较高的蛋白吸附Examples例如PTFE-Teflon聚四氟乙烯Naturallyhydrophobic天然疏水Mosthydrophobicpolymer大部分为疏水聚合物20进液最终产品深层澄清(Millistak+orPolygard)膜最终(Durapore0.22or0.45mm)表面预过滤(MilligardorPolysep-II)过滤系统配置21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过滤系统配置澄清过滤预过滤最终过滤22DepthSurfaceMembrane01RetentionCostCapacity最终过滤是昂贵的，因此应参加深层过滤和表面过滤来提高膜过滤的载量膜材料，表现及成本截流成本载量23过滤组合的优化---降低成本深层过滤的载量影响除菌过滤的能力载量与除菌能力呈负相关01000200030004000500060007000050010001500200025003000Prefilterloading(L/m2)Sterilecapacity(L/m2)0.00.51.01.52.02.53.03.54.002505007501000PrefilterLoading(L/m2)$/L“最低成本”最经济24收集10分