Liu, Haijing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 112-116). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.iii / 摘要 --- p.v / Table of contents --- p.vi / List of figures --- p.xii / List of tables --- p.xv / List of abbreviations --- p.xvi / Chapter / Chapter 1 --- Introduction / Chapter 1.1 --- Fermentation --- p.1 / Chapter 1.1.1 --- Biopharmaceutical production --- p.1 / Chapter 1.1.2 --- History of fermentation --- p.1 / Chapter 1.1.3 --- Fermentation Technology --- p.2 / Chapter 1.1.3.1 --- Fermentation process --- p.2 / Chapter 1.1.3.2 --- Fermenter --- p.4 / Chapter "1,1.3.3" --- Mode of fermentation process --- p.5 / Chapter 1.1.3.4 --- Bacterial growth --- p.6 / Chapter 1.1.4 --- High cell density fermentation for plasmid DNA production --- p.7 / Chapter 1.1.4.1 --- Porcine growth hormone releasing factor (pGRF) --- p.8 / Chapter 1.1.4.2 --- H5N1 avian influenza viruses DNA vaccine --- p.9 / Chapter 1.1.4.3 --- Fed-batch high-cell-density fermentation --- p.9 / Chapter 1.1.5 --- Fermentation process monitoring --- p.11 / Chapter 1.2 --- Near-infrared spectroscopy (NIRS) --- p.12 / Chapter 1.2.1 --- Basic near-infrared spectroscopy --- p.13 / Chapter 1.2.1.1 --- Rationale of near-infrared spectroscopy --- p.13 / Chapter 1.2.1.2 --- NIR spectra acquisition --- p.16 / Chapter 1.2.1.3 --- Interpretation of NIR spectra --- p.18 / Chapter 1.2.2 --- Multivariate calibration --- p.20 / Chapter 1.2.2.1 --- Why multivariate calibration --- p.22 / Chapter 1.2.2.2 --- The problem of collinearity --- p.25 / Chapter 1.2.2.3 --- Spectral range selection --- p.26 / Chapter 1.2.2.4 --- Signal optimization --- p.26 / Chapter 1.2.2.5 --- Spectral pretreatment --- p.27 / Chapter 1.2.2.6 --- Parameter selection --- p.28 / Chapter 1.2.3 --- Applications of NIRS in high cell density E. coli fermentation --- p.31 / Chapter 1.2.4 --- Adaptive calibration strategy --- p.33 / Chapter 1.3 --- Aims of study --- p.34 / Chapter 2 --- Materials and methods / Chapter 2.1 --- High cell density fermentation of plasmid DNA --- p.35 / Chapter 2.1.1 --- Fermentation system --- p.35 / Chapter 2.1.2 --- pGRF fermentation --- p.38 / Chapter 2.1.2.1 --- Prepare seed flask --- p.38 / Chapter 2.1.2.2 --- Reagents for bacterial culture by fermenter --- p.38 / Chapter 2.1.2.2.1 --- LB based complex fermentation medium --- p.38 / Chapter 2.1.2.2.2 --- Batch fermentation medium --- p.39 / Chapter 2.1.2.2.3 --- Feeding medium-1 --- p.41 / Chapter 2.1.2.2.4 --- Base feed --- p.41 / Chapter 2.1.2.3 --- Fermentation methods --- p.42 / Chapter 2.1.2.3.1 --- Fermenter set-up --- p.42 / Chapter 2.1.2.3.2 --- Inoculate seed culture into the fermenter --- p.43 / Chapter 2.1.2.3.3 --- Transfer the feeding medium --- p.44 / Chapter 2.1.2.3.4 --- Heat induction --- p.44 / Chapter 2.1.2.3.5 --- Fermentation harvest --- p.44 / Chapter 2.1.2.4 --- Scale-up fermentation and large scale production 45 / Chapter 2.1.3 --- H5N1 fermentation --- p.45 / Chapter 2.1.4 --- Reference analytical testing --- p.45 / Chapter 2.1.4.1 --- Optical density --- p.45 / Chapter 2.1.4.2 --- Cell dry weight --- p.45 / Chapter 2.1.4.3 --- Specific plasmid DNA yield --- p.46 / Chapter 2.1.4.3.1 --- Plasmid DNA isolation --- p.46 / Chapter 2.1.4.3.2 --- Plasmid DNA measurement --- p.46 / Chapter 2.1.4.3.3 --- Plasmid DNA identification --- p.46 / Chapter 2.1.4.4 --- Analysis of glycerol and acetate --- p.46 / Chapter 2.1.4.4.1 --- Standard samples --- p.46 / Chapter 2.1.4.4.2 --- Enzymatic test kits --- p.47 / Chapter 2.1.4.4.3 --- Automatic biochemistry analyzer --- p.47 / Chapter 2.1.5 --- Summary of all fermentation batches --- p.48 / Chapter 2.2 --- Full factorial design and semi-synthetic samples --- p.49 / Chapter 2.2.1 --- Adaptive calibration samples --- p.49 / Chapter 2.2.1.1 --- Matrix 1 calibration samples --- p.49 / Chapter 2.2.1.2 --- Matrix 2 calibration samples --- p.50 / Chapter 2.2.1.3 --- Matrix 3 calibration samples --- p.50 / Chapter 2.2.2 --- Summary of all samples --- p.51 / Chapter 2.3 --- NIR sample presentation and spectral acquisition --- p.52 / Chapter 2.3.1 --- NIR spectrophotometers --- p.52 / Chapter 2.3.2 --- Cuvettes for transmittance spectral acquisition --- p.53 / Chapter 2.3.3 --- Bottles for reflectance spectral acquisition --- p.54 / Chapter 2.3.4 --- Spectral acquisition --- p.55 / Chapter 2.3.4.1 --- Transmittance --- p.55 / Chapter 2.3.4.2 --- Reflectance --- p.55 / Chapter 2.4 --- Multivariate calibration and validation --- p.56 / Chapter 2.4.1 --- Spectral preprocessing --- p.56 / Chapter 2.4.2 --- Multivariate calibration --- p.57 / Chapter 2.4.3 --- Model validation --- p.57 / Chapter 3 --- Results and discussion / Chapter 3.1 --- Sample presentation and NIR spectrum --- p.59 / Chapter 3.1.1 --- Transmission measurement --- p.60 / Chapter 3.1.2 --- Reflectance measurement --- p.63 / Chapter 3.1.3 --- Spectral responses and pre-treatment method --- p.64 / Chapter 3.1.4 --- Design of experiments for calibration sample preparation --- p.67 / Chapter 3.1.5 --- Summary --- p.68 / Chapter 3.2 --- Adaptive calibration --- p.69 / Chapter 3.2.1 --- Selection of Multivariate calibration model --- p.70 / Chapter 3.2.1.1 --- Matrix 1 calibration models --- p.70 / Chapter 3.2.1.2 --- Matrix 2 calibration models --- p.74 / Chapter 3.2.1.3 --- Matrix 3 calibration models --- p.76 / Chapter 3.2.1.4 --- Summary --- p.78 / Chapter 3.2.2 --- Model validation --- p.79 / Chapter 3.2.2.1 --- Performance of Reference analytical methods --- p.79 / Chapter 3.2.2.1.1 --- Enzymatic test kits --- p.79 / Chapter 3.2.2.1.2 --- Automatic biochemistry anaylyzer (Bioprofile) --- p.81 / Chapter 3.2.2.1.3 --- Summary --- p.83 / Chapter 3.2.2.2 --- Model validation using external test samples --- p.83 / Chapter 3.2.2.2.1 --- Matrix 1 models --- p.83 / Chapter 3.2.2.2.2 --- Matrix 2 models --- p.87 / Chapter 3.2.2.2.3 --- Matrix 3 models --- p.89 / Chapter 3.2.2.2.4 --- Overall NIR measurement errors --- p.90 / Chapter 3.2.2.2.5 --- Summary --- p.91 / Chapter 3.3 --- Use of calibrated NIRS in at-line monitoring and control of fermentation --- p.93 / Chapter 3.3.1 --- Analysis of small-scale fermentation --- p.94 / Chapter 3.3.1.1 --- pGRF plasmid DNA production --- p.94 / Chapter 3.3.1.2 --- H5N1 plasmid DNA production --- p.95 / Chapter 3.3.1.3 --- Summary --- p.97 / Chapter 3.3.2 --- Analysis of large scale fermentation --- p.97 / Chapter 3.3.2.1 --- 30 L clinical production of H5N1 plasmid DNA --- p.97 / Chapter 3.3.2.2 --- 80 L scale-up production of H5N1 plasmid DNA --- p.99 / Chapter 3.3.2.3 --- Summary --- p.100 / Chapter 3.3.3 --- Effective control of fermentation production using at-line NIR analysis --- p.101 / Chapter 3.3.3.1 --- At-line monitoring of Batch 11 --- p.101 / Chapter 3.3.3.2 --- At-line monitoring of Batch 12 X --- p.102 / Chapter 3.3.3.3 --- Summary --- p.104 / Chapter 3.4 --- General discussion and conclusion --- p.105 / Chapter 3.5 --- Future prospects --- p.108 / References --- p.112 / Appendix 1 --- p.117 / Appendix 2 --- p.118 / Appendix 3 --- p.123 / Appendix 4 --- p.131 / Appendix 5 --- p.134
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_327213 |
| Date | January 2010 |
| Contributors | Liu, Haijing., Chinese University of Hong Kong Graduate School. Division of Life Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, xvii 134 leaves : ill. (chiefly col.) ; 30 cm. |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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