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二O二五年九月BioseparationEngineering李健海洋食品与生物工程学院课程性质及建设历程集美大学开设生物工程专业2000集美大学校级特色专业福建省服务产业特色专业福建省一流本科课程200820162020福建省一流专业建设点20232025国家一流本科课程课程性质及建设历程教学理念及过程陈超翔副教授博士毕业于厦门大学化学生物学专业陈玉磊副教授博士毕业于浙江大学细胞生物学专业UniversityofMassachusetts访问学者课程团队李健教授博士毕业于厦门大学微生物学专业StonyBrookUniversity博士后课程团队所获荣誉授课方式授课内容学时数线上基础理论知识与应用10线下22企业导师专题讨论
4英文文献汇报4合计40课程安排及考试方式考试组成组成总成绩占比期末考试成绩基本知识(60%)60%阅读英文文献(40%)平时成绩线上学习(15%)40%文献汇报(15%)作业(10%)考勤规定:缺席6次及以上不能参加期末考试。每缺课一次平时成绩总分扣3分。References(1)《AdvancesinProteinPurification》,CarolineGardner,CallistoReference,2015.(2)《ProteinPurification:PrinciplesandTrends》,IconceptPress,2016(3)《生物分离与纯化技术》,李从军,郭丽娜,四川大学出版社,2018.(4)《生物分离科学与工程》,余润兰,中南大学出版社,2018.(5)《生物技术在海洋生物资源开发中的应用》,王梁华,焦炳华,科学出版社,2017.(6)《生物分离工程》,胡永红,李凤珠,韩矅平主编,华中科技大学出版社,2015.(7)《生物分离工程》,孙彦,化学工业出版社,2005(8)《PROTEINEXPRESSIONANDPURIFICATION》,ACADEMICPRESSINCELSEVIERSCIENCE,杂志Textbook《生物分离工程》,李健、陈超翔主编,曹敏杰主审.化学工业出版社,2025;福建省“十四五”规划教材、化学工业出版社“十四五”普通高等教育规划教材BiochemicalProductsChapter1introductionChapter2filtration(过滤)andcentrifugation(离心)Chapter3celldisruption(细胞破碎)Chapter4crystallization(结晶)andprecipitation(沉淀)Chapter5membraneseparation(膜分离)Chapter6extraction(萃取)Chapter7chromatography(色谱、层析)Chapter8electrophoresis(电泳)andmagneticbioseparation(磁性生物分离)Chapter9solventremoval(溶剂去除)anddrying(干燥)Chapter1Introduction1.1Introduction1.2ClassificationofbioseparationSteps1.3Bioseparationprocessselection1.4Developmentsofbioseparationprocess基本要求:掌握生物分离工程在生物工程领域的地位,生物分离过程的特点以及生物分离过程的分类。了解生物分离过程选择原则及发展。重点:准确理解生物分离过程的特点;生化分离工程的一般流程和单元操作难点:生物分离过程的特点;生化分离工程的一般流程。
1.1introductionBiochemicalengineeringBioprocessingDownstreambioprocessing(bioseparationengineering)CharacteristicofBioseparationsBiochemicalengineering(生化工程)isconcernedwithconductingbiologicalprocesses
onanindustrialscale.Thisareacombinebiologicalsciences
withchemicalengineering.Bioprocessing(生物过程):manufactureofbiologicalproducts.IndustrialchemicalsAgrochemicalsPharmaceuticalsFoodandfoodadditivesNutraceuticalsDiagnosticproductsCommoditychemicalsLaboratoryreagentsCosmeticproductsBioprocessingincludesthreeessentialstages:upstreambioprocessing:cellularexpressionmidstreambioprocessing:bioreactordownstreambioprocessing:productpurification
Downstreamprocessingorbioseparationengineering(生物分离工程):systematicstudyofthescientificandengineeringprinciples
utilizedfortherecovery(提取),isolation(分离),purification(纯化)andpolishing(精制)ofbiologicalproducts.CharacteristicsofbioseparationBiologicalproductsexistinhighlydilutedaqueoussolutionsinthebioreactor.Mostofbiologicalproductsareunstable.Biologicalproductsrequirehighquality
(safety,identity/purityandpotency/activity)Thecomponentsinthefeedarecomplicate.Manycurrentcommercialproductsaremanufacturedinbatches.尿激酶干扰素紫杉醇生长激素荧光素酶胰岛素肾素四环素青霉素胶原蛋白丁醇乙醇山梨糖醇柠檬酸乳酸生物反应器细胞收集细胞破碎提取纯化产品制剂Bioseparationprocessflowdiagramforintracellularproducts1.2
ClassificationofbioseparationSteps1.2
ClassificationofbioseparationStepssolid-liquidseparationRecoveryPurification
(polish)finalproductformulationexamplessolid-liquidseparationOperationspretreatment(预处理)filtration(过滤),centrifugation(离心),microfiltration(微滤),sedimentation(沉降)celldisruption(细胞破碎)(necessarywhenthedesiredproductisintracellular.)Relativelylittleproductconcentrationorimprovementofproductqualityoccurs.
RecoveryOperationsadsorption(吸附)extraction(萃取)precipitation(沉淀)membraneseparation
(膜分离)Thesesteps,whicharerelativelynonspecific,removematerialsofwidelydivergentpropertiescomparedtothedesiredproduct.(以上分离过程不具备特异性,只是进行初分)Appreciableconcentrationandproductqualityincreasesusuallyoccur.(可提高产物浓度和质量)purificationOperationschromatography(色谱)electrophoresis(电泳)crystallization(结晶)Theseprocessingtechnologyarehighlyselective
fortheproductandremoveimpuritiesofsimilarchemicalfunctionalityandphysicalproperties.(以上技术具有产物的高选择性和杂质的去除性)finalproductformulationOperationsconcentration(浓缩)drying(干燥)sterilize(灭菌)removingpyrogen(去除热源)addingexcipients(加赋形剂)
thefinalstateinwhichtheyarepackaged,stored,anddispensed.Asuccessfulformulationprocesswillofferbothefficiencyandsafety.Theresultingproductmustremainstable.BioreactorfluidwithcellsContinuouscentrifugation100000MW
membraneAffinityChromatographyUnboundmaterialCellsSterilefiltrationformulationMembraneconcentrationIgGproductIgGelutedSupernatantFigure1.1Recoveryandpurificationofmonoclonalantibodies单克隆抗体MW:160000daltons,分泌胞外蛋白A或蛋白G超滤超滤BioreactorfluidwithcellsfiltrationActivatedcarbontreatmentfiltrationAcetone丙酮andwaterandsodiumorpotassiumacetate
乙酸钠、乙酸钾Figure1.2Recoveryandpurificationofpeniclillin青霉素Amylacetate乙酸戊酯ExtractionspH2-3dryingFiltrationFiltrationcrystallizationWashingproductIsopropanol异丙醇orbutanol丁醇SpentsolventSpentsolventT=5℃CaCl2andpolyelectrolyte聚合电解质filtrateextractSpentsolventCarbonandimpuritiesCentrifugationorfiltrationpH-adjustedAdsorptionbyacidicresinEvaporation
HClHCl带+2静电荷dryingAnimalfeedproductElute洗脱Figure1.3animalandfood-gradel-lysinerecoveryandpurificationAnimalfeedorfood-gradeproductsfiltrationcrystallizationfiltrationdryingFood-gradeproductpH-adjusted阳离子交换树脂,氯化铵洗脱L-lys-HClActivatedcarbon1.3bioseparationprocessselectionhighthroughput/productivitylowcostusingthefewestnumberofprocessstepssequenceofbioseparationstepsqualityrequirementsandregulatoryenvironmentproductionscalecomponentsoffeedlocationandnatureofproductwasteproductionanddisposalcostCapitalcostDesigning,purchasing,installingapieceofbioseparationequipmentOperatingcostmaintenanceutilitiessuchaselectricity,steamandcompressedairlaborrawmaterialsTherecoveryplantusuallyrepresentsamajorinvestmentand,consequentlytheseparationscostasubstantialfractionofthetotalcostofthefinalproduct.(分离过程的成本占产品总投资的大部分)ProductBioseparationcost(%)Solventse.g.ethanol(乙醇),acetone(丙酮)15-20Cells,e.g.bakersyeast(面包酵母),brewersyeast(啤酒酵母)20-25Crudecellularextracts,e.g.yeastextract(酵母提取物)20-25Organicsacids,e.g.citricacid(柠檬酸),lacticacid(乳酸)30-40Vitaminsandaminoacids
e.g.lysine,ascorbicacid(维生素C)30-40Antibiotics,e.g.penicillins20-60Industrialenzymes,e.g.glucoseisomerase(葡萄糖异构酶)40-65Non-recombinanttherapeuticproteins,e.g.pancreatin(胰酶),papain(木瓜蛋白酶)50-70Monoclonalantibodies50-70Nucleicacidbasedproducts60-80Plasmaproteins,humanalbumin,humanimmunoglobulins70-80usingthefewestnumberofprocessstepsInordertogetahighproductivity,IncreasetherecoveryofeachbioseparationstepReduce
the
number
ofoperationstepsForexample:2steps90%Recovery:90%×90%=81
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