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1、HandbookDesign of experiments in protein production and purification ContentsIntroduction 4Symbols used in this handbook 5Traditional experimental design versus DoE 6DoE nomenclature 8DoE at a glance 8History of DoE 10 Industrial applications 11DoE in protein production and purification 12Upstream p

2、rocess development 14A strategy for protein purification 15The individual purification steps 15Principles of combining purification steps 16Principles of selection of chromatography media 17Factors and responses when optimizing protein 18 purification Responses 18 Capture 19 Intermediate purificatio

3、n 19 Polishing 20 Chromatography step optimization 20Process development and characterization 21Quality by design(QbD)22Protein purification tools for DoE 23 Process development tools 23 Other tools for parallel protein purification 25Design of experiments,step-by-step 26Gather information before st

4、arting 27Step 1.Define objective,factors,and ranges 28 Objectives 29 Screening 29 Optimization 30 Robustness testing 30 Design considerations 30 Factors and factor ranges 30 Quantitative and qualitative factors 32 Controllable and uncontrollable factors 32 Structured approach to selecting factors 32

5、 Independent measurements of factor effects 33Step 2.Define responses and measurement systems 34 Quantitative and qualitative responses 34 Measurement system requirements 35Step 3.Create the design 36 Design resolution 38 Number of experiments needed 38 Systematic bias 39 Order of experiments 39 Rep

6、lication of experiments 40 Arranging experiments into blocks 40 Experimental design center points 41 Evaluation of design quality(condition number)42Step 4.Perform experiments 43 DoE with UNICORN software and KTA systems 43Configuration of KTA systems 44Step 5.Create model 44 Signal and noise 46 Mod