Bioprocess optimization using design-of-experiments methodology

Mandenius, Carl‐Fredrik; Brundin, Anders

doi:10.1002/btpr.67

Cited by 422Optimal Experimental Design MethodsViral Infectious Diseases and Gene Expression in InsectsFluid Dynamics and Mixing

Bioprocess optimization using design-of-experiments methodology

Mandenius, Carl‐Fredrik, Brundin, Anders·2008·Biotechnology Progress

DOI 10.1002/btpr.67

Open this paper in CoChat — free account

Abstract

This review surveys recent applications of design‐of‐experiments (DoE) methodology in the development of biotechnological processes. Methods such as factorial design, response surface methodology, and (DoE) provide powerful and efficient ways to optimize cultivations and other unit operations and procedures using a reduced number of experiments. The multitude of interdependent parameters involved within a unit operation or between units in a bioprocess sequence may be substantially refined and improved by the use of such methods. Other bioprocess‐related applications include strain screening evaluation and cultivation media balancing. In view of the emerging regulatory demands on pharmaceutical manufacturing processes, exemplified by the process analytical technology (PAT) initiative of the United States Food and Drug Administration, the use of experimental design approaches to improve process development for safer and more reproducible production is becoming increasingly important. Here, these options are highlighted and discussed with a few selected examples from antibiotic fermentation, expanded bed optimization, virus vector transfection of insect cell cultivation, feed profile adaptation, embryonic stem cell expansion protocols, and mammalian cell harvesting.

Integrity signals

Registry

Crossref · 10.1002/btpr.67

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Characterization of the impact of changes to process parameters on critical quality attributes, such as by using design of experiments, improves understanding of the process, enables its optimization, and ultimately assures product quality by design.
“The characterization of the impact of changes to process parameters on these CQAs, such as by using design of experiments,9 improves understanding of the process, enables its optimization, and ultimately assures product quality by design (Table 1).10, 11, 12”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [9]

Statistics for Experimenters: An Introduction to Design, Data Analysis and Model Building.
Pearce, S. C., Box, G. E. P., Hunter, W. G., & Hunter, J. S. (1979) · Biometrics · doi:10.2307/2530361 · Cited by 2,003 · see citing works
Chemometrics: Data Analysis for the Laboratory and Chemical Plant
Brereton, R. G. (2003) · Thammasat University Digital Collections · Cited by 1,356 · see citing works
Design and Analysis of Experiments
Hinkelmann, K. H., & Kempthorne, O. (2005) · Wiley series in probability and statistics · doi:10.1002/0471709948 · Cited by 963 · see citing works
Chemometrics
Brereton, R. G. (2003) · Wiley eBooks · doi:10.1002/0470863242 · Cited by 861 · see citing works
Design and Analysis of Factorial Experiments
Yates, F. (1958) · Rothamsted Repository (Rothamsted Repository) · Cited by 472 · see citing works
Proposed minimum reporting standards for data analysis in metabolomics
Goodacre, R., Broadhurst, D., Smilde, A. K., Kristal, B. S., Baker, J. D., Beger, R. D., Bessant, C., Connor, S. C., Capuani, G., Craig, A., et al. (2007) · Metabolomics · doi:10.1007/s11306-007-0081-3 · Cited by 441 · see citing works
Statistics for Experimenters: Design, Innovation and Discovery
Pigeon, J. G. (2006) · Technometrics · doi:10.1198/tech.2006.s379 · Cited by 437 · see citing works
Design and Optimization in Organic Synthesis
(1992) · Data handling in science and technology · doi:10.1016/s0922-3487(08)x7011-x · Cited by 404 · see citing works
The Design and Analysis of Factorial Experiments
FISHER, R. A. (1938) · Nature · doi:10.1038/142090a0 · Cited by 295 · see citing works
Experimental Design for Fermentation Media Development: Statistical Design or Global Random Search?
Weuster‐Botz, D. (2000) · Journal of Bioscience and Bioengineering · doi:10.1016/s1389-1723(01)80027-x · Cited by 220 · see citing works
Response surface methodological approach to optimize the nutritional parameters for neomycin production by Streptomyces marinensis under solid-state fermentation
Kunamneni, A., Ellaiah, P., Srinivasulu, B., Devi, R. B., & Adinarayana, G. (2003) · Process Biochemistry · doi:10.1016/s0032-9592(03)00057-8 · Cited by 180 · see citing works
Effect of inhibitory compounds found in biomass hydrolysates on growth and xylose fermentation by a genetically engineered strain of S. cerevisiae
Helle, S. S., Cameron, D., Lam, J., White, B., & Duff, S. J. B. (2003) · Enzyme and Microbial Technology · doi:10.1016/s0141-0229(03)00214-x · Cited by 165 · see citing works
Optimization of the medium composition for production of mycelial biomass and exo-polymer by Grifola frondosa GF9801 using response surface methodology
Cui, F., Li, Y., Xu, Z., Xu, H., Sun, K., & Tao, W. Y. (2005) · Bioresource Technology · doi:10.1016/j.biortech.2005.05.005 · Cited by 146 · see citing works
Optimization of astaxanthin production by Phaffia rhodozyma through factorial design and response surface methodology
Ramı́rez, J., Pulido, H. G., & Gschaedler, A. (2001) · Journal of Biotechnology · doi:10.1016/s0168-1656(01)00279-6 · Cited by 138 · see citing works
Optimization of inulinase production by solid-state fermentation using sugarcane bagasse as substrate
Mazutti, M. A., Bender, J. P., Treichel, H., & Luccio, M. D. (2005) · Enzyme and Microbial Technology · doi:10.1016/j.enzmictec.2005.09.008 · Cited by 112 · see citing works
Bacteriocin production by Bacillus licheniformis strain P40 in cheese whey using response surface methodology
Cladera‐Olivera, F., Caron, G. R., & Brandelli, A. (2004) · Biochemical Engineering Journal · doi:10.1016/j.bej.2004.05.002 · Cited by 108 · see citing works
Tobacco protein separation by aqueous two-phase extraction
Balasubramaniam, D., Wilkinson, C. A., Cott, K. E. V., & Zhang, C. (2003) · Journal of Chromatography A · doi:10.1016/s0021-9673(02)01900-3 · Cited by 99 · see citing works
Hybrid elementary flux analysis/nonparametric modeling: application for bioprocess control
Teixeira, A. P., Alves, C., Alves, P., Carrondo, M., & Oliveira, R. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-30 · Cited by 98 · see citing works
Optimizing lipase production of Burkholderia sp. by response surface methodology
Liu, C., Lu, W.-B., & Chang, J. (2006) · Process Biochemistry · doi:10.1016/j.procbio.2006.04.013 · Cited by 85 · see citing works
Optimization of Amylase and Protease Production from Aspergillus awamori in Single Bioreactor Through EVOP Factorial Design Technique
Negi, S., & Banerjee‬‬‬‬‬‬‬‬‬, R. (2005) · Cited by 76 · see citing works
Influence of temperature and pH on Saccharomyces bayanus var. uvarum growth; impact of a wine yeast interspecific hybridization on these parameters
Serra, A., Strehaiano, P., & Taillandier, P. (2005) · International Journal of Food Microbiology · doi:10.1016/j.ijfoodmicro.2005.03.006 · Cited by 74 · see citing works
Medium optimization for hen egg white lysozyme production by recombinant Aspergillus niger using statistical methods
Gheshlaghi, R., Scharer, J. M., Moo‐Young, M., & Douglas, P. L. (2005) · Biotechnology and Bioengineering · doi:10.1002/bit.20474 · Cited by 70 · see citing works
Optimization of recombinant aminolevulinate synthase production in Escherichia coli using factorial design
Xie, L., Hall, D. B., Eiteman, M. A., & Altman, E. (2003) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-003-1388-2 · Cited by 67 · see citing works
Optimization of carotenoid production by Rhodotorula glutinis using statistical experimental design
Park, P. K., Cho, D. H., Kim, E.-K., & Chu, K. H. (2005) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-004-1891-3 · Cited by 66 · see citing works
Potential of solid-state fermentation enzymes of Aspergillus oryzae in biobleaching of paper pulp
Szendefy, J., Szakács, G., & Christopher, L. P. (2006) · Enzyme and Microbial Technology · doi:10.1016/j.enzmictec.2006.06.016 · Cited by 60 · see citing works
Polyglutamic acid (PGA) production by Bacillus sp. SAB-26: application of Plackett–Burman experimental design to evaluate culture requirements
Soliman, N. A.-M., Berekaa, M. M., & Abdel-Fattah, Y. R. (2005) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-005-1982-6 · Cited by 58 · see citing works
Optimization of γ-polyglutamic acid production byBacillus subtilis ZJU-7 using a surface-response methodology
Shi, F., Xu, Z., & Cen, P. (2006) · Biotechnology and Bioprocess Engineering · doi:10.1007/bf02932039 · Cited by 54 · see citing works
Effects of process parameters on heterologous protein production in Aspergillus niger fermentation
Wang, L., Ridgway, D., Gu, T., & Moo‐Young, M. (2003) · Journal of Chemical Technology & Biotechnology · doi:10.1002/jctb.898 · Cited by 53 · see citing works
Effect of inhibition treatment, type of inocula, and incubation temperature on batch H2 production from organic solid waste
Vazquez, I. V., Ríos‐Leal, E., Muñoz-Páez, K. M., Carmona-Martínez, A. A., & Poggi-Varaldo, H. M. (2006) · Biotechnology and Bioengineering · doi:10.1002/bit.20891 · Cited by 49 · see citing works
Optimization of medium composition for the production of clavulanic acid by Streptomyces clavuligerus
Wang, Y.-H., Yang, B., Ren, J., Dong, M.-L., Liang, D., & Xu, A.-L. (2005) · Process Biochemistry · doi:10.1016/j.procbio.2004.04.010 · Cited by 45 · see citing works
Quantitative screening of embryonic stem cell differentiation: Endoderm formation as a model
Chang, K. H., & Zandstra, P. W. (2004) · Biotechnology and Bioengineering · doi:10.1002/bit.20242 · Cited by 43 · see citing works
Microplates with integrated oxygen sensing for medium optimization in animal cell culture
Deshpande, R. R., Wittmann, C., & Heinzle, E. (2004) · Cytotechnology · doi:10.1007/s10616-004-6401-9 · Cited by 42 · see citing works
Optimization of culture conditions for CO2 fixation by a chemoautotrophic microorganism, strain YN-1 using factorial design
Kwak, K.-O., Jung, S.-J., Chung, S.-Y., Kang, C.-M., Huh, Y., & Bae, S. (2006) · Biochemical Engineering Journal · doi:10.1016/j.bej.2006.05.001 · Cited by 42 · see citing works
A study of antifungal antibiotic production by Streptomyces chattanoogensis MTCC 3423 using full factorial design
Gupte, M., & Kulkarni, P. R. (2002) · Letters in Applied Microbiology · doi:10.1046/j.1472-765x.2002.01119.x · Cited by 40 · see citing works
Optimization of Nisin Production by Lactococcus lactis
Penna, T. C. V., & Moraes, D. A. (2002) · Humana Press eBooks · doi:10.1007/978-1-4612-0119-9_63 · Cited by 37 · see citing works
Effect of culture conditions on production of butter flavor compounds by Pediococcus pentosaceus and Lactobacillus acidophilus in semisolid maize-based cultures
Escamilla-Hurtado, M. L., VALDES-MARTINEZ, S. E., Soriano-Santos, J., Gómez-Pliego, R., Verde-Calvo, J. R., Reyes-Dorantes, A., & Tomasini-Campocosio, A. (2005) · International Journal of Food Microbiology · doi:10.1016/j.ijfoodmicro.2005.04.014 · Cited by 35 · see citing works
Optimization of a Bifidobacterium longum production process
Kiviharju, K., LEISOLA, M. S. A., & Eerikäinen, T. (2005) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2005.02.007 · Cited by 32 · see citing works
Production of chitinolytic enzymes by Serratia marcescens QMB1466 using various chitinous substrates
Green, A. T., Healy, M. G., & Healy, A. (2004) · Journal of Chemical Technology & Biotechnology · doi:10.1002/jctb.1145 · Cited by 28 · see citing works
Effect of salt nutrients on mannitol production by Lactobacillus intermedius NRRL B-3693
Badal Chandra, S. A. H. A. (2006) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-006-0140-1 · Cited by 27 · see citing works
Response surface optimization of temperature and pH for the growth of Pachysolen tannophilus
Roebuck, K., Brundin, A., & Johns, M. (1995) · Enzyme and Microbial Technology · doi:10.1016/0141-0229(94)00046-t · Cited by 27 · see citing works
Self-citation
Optimization of 6‐aminopenicillanic acid (6‐APA) production by using a new immobilized penicillin acylase
Torres‐Bacete, J., Arroyo, M., Torres‐Guzmán, R., de la Mata, I., Castillón, M. P., & Acebal, C. (2000) · Biotechnology and Applied Biochemistry · doi:10.1042/ba20000042 · Cited by 26 · see citing works
Rational DOE protocols for 96-well plates
Olsson, I.-M., Johansson, E., Berntsson, M., Eriksson, L., Gottfries, J., & Wold, S. (2006) · Chemometrics and Intelligent Laboratory Systems · doi:10.1016/j.chemolab.2006.01.005 · Cited by 24 · see citing works
Medium optimization for meilingmycin production by Streptomyces nanchangensis using response surface methodology
Zhuang, Y., Chen, B., Chu, J., & Zhang, S. (2005) · Process Biochemistry · doi:10.1016/j.procbio.2005.07.004 · Cited by 23 · see citing works
Factorial designs: an efficient approach to choosing the main factors influencing growth and hydrolase production by Tetrahymena thermophila
Coninck, J. D., Leclercq, B., Exbrayat, J., & Duyme, F. (2004) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-004-0135-8 · Cited by 22 · see citing works
The effect of nitrogen source on yield and glycosylation of a human cystatin C mutant expressed in Pichia pastoris
Pritchett, J., & Baldwin, S. A. (2004) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-004-0181-2 · Cited by 20 · see citing works
Evaluation of the effects and interactions of mixing and oxygen transfer on the production of Fab’ antibody fragments in Escherichia coli fermentation with gas blending
García‐Arrazola, R., Dawson, P., Buchanan, I., Doyle, B., Fearn, T., Titchener-Hooker, N. J., & Baganz, F. (2005) · Bioprocess and Biosystems Engineering · doi:10.1007/s00449-005-0414-4 · Cited by 14 · see citing works
Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry for metabolic flux analyses using isotope‐labeled ethanol
Hollemeyer, K., Velagapudi, V., Wittmann, C., & Heinzle, E. (2007) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.2840 · Cited by 13 · see citing works
Application of mathematical optimization methods in microbiology
Pilát, P., Voteuba, J., Doberský, P., & Prokop, A. (1976) · Folia Microbiologica · doi:10.1007/bf02876966 · Cited by 12 · see citing works
Optimization of Culture Medium and Conditions for Penicillin Acylase Production by Streptomyces lavendulae ATCC 13664
Torres‐Bacete, J., Arroyo, M., Torres‐Guzmán, R., de la Mata, I., Acebal, C., & Castillón, M. P. (2005) · Applied Biochemistry and Biotechnology · doi:10.1385/abab:126:2:119 · Cited by 12 · see citing works
Optimization of extracellular fungal peroxidase production by 2 Coprinus species
Ikehata, K., Pickard, M. A., Buchanan, I., & Smith, D. W. (2004) · Canadian Journal of Microbiology · doi:10.1139/w04-098 · Cited by 10 · see citing works
Culture Medium Optimization and Scale-Up for Microbial Fermentations
Connors, N. C. (2003) · doi:10.1007/978-1-59259-346-0_7 · Cited by 9 · see citing works
Multiple parameter optimization for the maximization of hydrogen production by Enterobacter cloacae DM11
Sen, D., & Das, D. (2005) · Journal of Scientific & Industrial Research · Cited by 9 · see citing works
High-throughput Fed-batch Production of Affibody® molecules in a novel Multi-fermentor system
Larsson, J. E. (2005) · KTH Publication Database DiVA (KTH Royal Institute of Technology) · Cited by 2 · see citing works
Particle Contamination of Salvage Blood Plasma in Cardiac Surgery
Engström, K. G. (2004) · Transfusion Medicine and Hemotherapy · doi:10.1159/000080403 · Cited by 1 · see citing works

Flagged first, then by citations

1 of the 55 references couldn’t be matched to a known paper.

Sorted by citations

Multivariate data analysis in pharmaceutics: A tutorial review
Rajalahti, T., & Kvalheim, O. M. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.02.019 · Cited by 770 · see citing works
Animal‐cell culture media: History, characteristics, and current issues
Yao, T., & Asayama, Y. (2017) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12024 · Cited by 538 · see citing works
Digital Twins in Pharmaceutical and Biopharmaceutical Manufacturing: A Literature Review
Chen, Y., Yang, O., Sampat, C., Bhalode, P., Ramachnadran, R., & Ierapetritou, M. (2020) · Processes · doi:10.3390/pr8091088 · Cited by 295 · see citing works
Bioprocessing in the Digital Age: The Role of Process Models
Narayanan, H., Luna, M. F., von Stosch, M., Bournazou, M. N. C., Polotti, G., Morbidelli, M., Butté, A., & Sokolov, M. (2019) · Biotechnology Journal · doi:10.1002/biot.201900172 · Cited by 254 · see citing works
Microalgal Heterotrophic and Mixotrophic Culturing for Bio-refining: From Metabolic Routes to Techno-economics
Perez‐Garcia, O., & Yoav Bashan, A. (2015) · Springer eBooks · doi:10.1007/978-3-319-20200-6_3 · Cited by 239 · see citing works
Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications
Read, E. K., Park, J. T., Shah, R. B., Riley, B. S., Brorson, K., & Rathore, A. S. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22528 · Cited by 217 · see citing works
Design of experiments and regression modelling in food flavour and sensory analysis: A review
Yu, P., Low, M. Y., & Zhou, W. (2017) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2017.11.013 · Cited by 205 · see citing works
Process analytical technology (PAT) for biopharmaceutical products: Part II. Concepts and applications
Read, E. K., Shah, R. B., Riley, B. S., Park, J. T., Brorson, K., & Rathore, A. S. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22529 · Cited by 202 · see citing works
“Humanized” Stem Cell Culture Techniques: The Animal Serum Controversy
Tekkatte, C., Gunasingh, G. P., Cherian, K. M., & Sankaranarayanan, K. (2011) · Stem Cells International · doi:10.4061/2011/504723 · Cited by 198 · see citing works
Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies
Gimpel, A. L., Katsikis, G., Sha, S., Maloney, A. J., Hong, M. S., Nguyen, T. N. T., Wolfrum, J., Springs, S. L., Sinskey, A. J., Manalis, S. R., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.010 · Cited by 185 · see citing works
Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles
Brumano, L. P., da Silva, F. V. S., Costa-Silva, T. A., Apolinário, A. C., Santos, J. H. P. M., Kleingesinds, E. K., Monteiro, G., Rangel‐Yagui, C. D. O., Benyahia, B., & Pessoa, A. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00212 · Cited by 189 · see citing works
High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization
Kastner, E., Kaur, R., Lowry, D., Moghaddam, B., Wilkinson, A., & Perrie, Y. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.10.030 · Cited by 180 · see citing works
Conversion of Chitin to Defined Chitosan Oligomers: Current Status and Future Prospects
Schmitz, C., Auza, L. G., Koberidze, D., Rasche, S., Fischer, R., & Bortesi, L. (2019) · Marine Drugs · doi:10.3390/md17080452 · Cited by 173 · see citing works
Microbioreactor Systems for Accelerated Bioprocess Development
Hemmerich, J., Noack, S., Wiechert, W., & Oldiges, M. (2017) · Biotechnology Journal · doi:10.1002/biot.201700141 · Cited by 170 · see citing works
Biological and chemical diversity go hand in hand: Basidiomycota as source of new pharmaceuticals and agrochemicals
Sandargo, B., Chepkirui, C., Cheng, T., Chaverra-Muñoz, L., Thongbai, B., Stadler, M., & Hüttel, S. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.01.011 · Cited by 151 · see citing works
Concise Review: Process Development Considerations for Cell Therapy
Campbell, A., Brieva, T. A., Raviv, L., Rowley, J. A., Niß, K., Brandwein, H. J., Oh, S., & Karnieli, O. (2015) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0294 · Cited by 150 · see citing works
Robo-Lector – a novel platform for automated high-throughput cultivations in microtiter plates with high information content
Huber, R., Ritter, D., Hering, T., Hillmer, A.-K., Kensy, F., Müller, C., Wang, L., & Büchs, J. (2009) · Microbial Cell Factories · doi:10.1186/1475-2859-8-42 · Cited by 146 · see citing works
A perspective on PSE in pharmaceutical process development and innovation
Gernaey, K. V., Cervera-Padrell, A. E., & Woodley, J. M. (2012) · Computers & Chemical Engineering · doi:10.1016/j.compchemeng.2012.02.022 · Cited by 143 · see citing works
Optimization of Protein Expression in Mammalian Cells
Hunter, M., Yuan, P., Vavilala, D. T., & Fox, M. (2018) · Current Protocols in Protein Science · doi:10.1002/cpps.77 · Cited by 128 · see citing works
Amino acids in the cultivation of mammalian cells
Salazar, A., Keusgen, M., & von Hagen, J. (2016) · Amino Acids · doi:10.1007/s00726-016-2181-8 · Cited by 124 · see citing works
A current assessment on the production of bacterial keratinases
Daroit, D. J., & Brandelli, A. (2013) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2013.794768 · Cited by 126 · see citing works
Design of experiments applications in bioprocessing: Concepts and approach
Kumar, V., Bhalla, A., & Rathore, A. S. (2013) · Biotechnology Progress · doi:10.1002/btpr.1821 · Cited by 126 · see citing works
Improving Metabolic Pathway Efficiency by Statistical Model-Based Multivariate Regulatory Metabolic Engineering
Xu, P., Rizzoni, E. A., Sul, S.-Y., & Stephanopoulos, G. N. (2016) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00187 · Cited by 123 · see citing works
Predictive models for transient protein expression in tobacco ( Nicotiana tabacum L.) can optimize process time, yield, and downstream costs
Buyel, J. F., & Fischer, R. (2012) · Biotechnology and Bioengineering · doi:10.1002/bit.24523 · Cited by 124 · see citing works
Leveraging advances in biology to design biomaterials
Darnell, M., & Mooney, D. J. (2017) · Nature Materials · doi:10.1038/nmat4991 · Cited by 122 · see citing works
Hydrogel Design of Experiments Methodology to Optimize Hydrogel for iPSC‐NPC Culture
Lam, J., Carmichael, S. T., Lowry, W. E., & Segura, T. (2015) · Advanced Healthcare Materials · doi:10.1002/adhm.201400410 · Cited by 119 · see citing works
Characterization of Lipid Nanoparticles Containing Ionizable Cationic Lipids Using Design-of-Experiments Approach
Terada, T., Kulkarni, J. A., Huynh, A., Chen, S., van der Meel, R., Tam, Y. Y. C., & Cullis, P. R. (2021) · Langmuir · doi:10.1021/acs.langmuir.0c03039 · Cited by 120 · see citing works
Scale-up from microtiter plate to laboratory fermenter: evaluation by online monitoring techniques of growth and protein expression in Escherichia coli and Hansenula polymorpha fermentations
Kensy, F., Engelbrecht, C., & Büchs, J. (2009) · Microbial Cell Factories · doi:10.1186/1475-2859-8-68 · Cited by 116 · see citing works
Optimization of carbon and nitrogen sources for biomass and lipid production by Chlorella saccharophila under heterotrophic conditions and development of Nile red fluorescence based method for quantification of its neutral lipid content
Isleten-Hosoglu, M., Gultepe, I., & Elibol, M. (2012) · Biochemical Engineering Journal · doi:10.1016/j.bej.2011.12.001 · Cited by 114 · see citing works
Hybrid modeling as a QbD/PAT tool in process development: an industrial E. coli case study
von Stosch, M., Hamelink, J., & Oliveira, R. (2016) · Bioprocess and Biosystems Engineering · doi:10.1007/s00449-016-1557-1 · Cited by 106 · see citing works
Hyperparameter Tuning of Machine Learning Algorithms Using Response Surface Methodology: A Case Study of ANN, SVM, and DBN
Pannakkong, W., Thiwa-anont, K., Singthong, K., Parthanadee, P., & Buddhakulsomsiri, J. (2022) · Mathematical Problems in Engineering · doi:10.1155/2022/8513719 · Cited by 105 · see citing works
Creation of a High-Yield AAV Vector Production Platform in Suspension Cells Using a Design-of-Experiment Approach
Zhao, H., Lee, K.-J., Daris, M., Lin, Y., Wolfe, T., Sheng, J., Plewa, C., Wang, S., & Meisen, W. H. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.004 · Cited by 98 · see citing works
CHO cell line specific prediction and control of recombinant monoclonal antibody N‐glycosylation
Grainger, R. K., & James, D. C. (2013) · Biotechnology and Bioengineering · doi:10.1002/bit.24959 · Cited by 102 · see citing works
Challenges in industrial fermentation technology research
Formenti, L. R., Nørregaard, A., Bolic, A., Hernandez, D. A. Q., Hagemann, T., Heins, A., Larsson, H., Mears, L., Mauricio‐Iglesias, M., Krühne, U., et al. (2014) · Biotechnology Journal · doi:10.1002/biot.201300236 · Cited by 102 · see citing works
GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition
Enochson, L., Stenberg, J., Brittberg, M., & Lindahl, A. H. (2014) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2014.02.004 · Cited by 99 · see citing works
Fungal mycelium as leather alternative: A sustainable biogenic material for the fashion industry
Amobonye, A., Lalung, J., Awasthi, M., & Pillai, S. (2023) · Sustainable Materials and Technologies · doi:10.1016/j.susmat.2023.e00724 · Cited by 102 · see citing works
Towards a Digital Bioprocess Replica: Computational Approaches in Biopharmaceutical Development and Manufacturing
Smiatek, J., Jung, A., & Bluhmki, E. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2020.05.008 · Cited by 98 · see citing works
Model-assisted Design of Experiments as a concept for knowledge-based bioprocess development
Möller, J., Kuchemüller, K. B., Steinmetz, T., Koopmann, K. S., & Pörtner, R. (2019) · Bioprocess and Biosystems Engineering · doi:10.1007/s00449-019-02089-7 · Cited by 83 · see citing works
Additives and salts for dye-sensitized solar cells electrolytes: what is the best choice?
Bella, F., Sacco, A., Pugliese, D., Laurenti, M., & Bianco, S. (2014) · Journal of Power Sources · doi:10.1016/j.jpowsour.2014.04.088 · Cited by 87 · see citing works
Applications of machine learning in antibody discovery, process development, manufacturing and formulation: Current trends, challenges, and opportunities
Khuat, T. T., Bassett, R., Otte, E. A., Grevis-James, A., & Gabryś, B. (2024) · Computers & Chemical Engineering · doi:10.1016/j.compchemeng.2024.108585 · Cited by 98 · see citing works
Formulation and Optimization of Nanoemulsions Using the Natural Surfactant Saponin from Quillaja Bark
Schreiner, T. B., Santamaria‐Echart, A., Ribeiro, A. M., Peres, A. M., Dias, M. M., Pinho, S. P., & Barreiro, M. F. (2020) · Molecules · doi:10.3390/molecules25071538 · Cited by 84 · see citing works
Adaptive Optimization of Chemical Reactions with Minimal Experimental Information
Reker, D., Hoyt, E. A., Bernardes, G. J. L., & Rodrigues, T. (2020) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2020.100247 · Cited by 83 · see citing works
Bioengineering Outlook on Cultivated Meat Production
Pajčin, I., Knežić, T., Azoulay, I. S., Vlajkov, V., Djisalov, M., Janjušević, L., Grahovac, J. A., & Gadjanski, I. (2022) · Micromachines · doi:10.3390/mi13030402 · Cited by 83 · see citing works
New improved method for fructooligosaccharides production by Aureobasidium pullulans
Dominguez, A., Nobre, C., Rodrigues, L. R., Peres, A. M., Torres, D. P. M., Rocha, I., Lima, N., & Teixeira, J. A. (2012) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2012.03.091 · Cited by 82 · see citing works
Bioprocessing Data for the Production of Marine Enzymes
Sarkar, S., Pramanik, A., Mitra, A., & Mukherjee, J. (2010) · Marine Drugs · doi:10.3390/md8041323 · Cited by 81 · see citing works
Model-based tools for optimal experiments in bioprocess engineering
Abt, V., Barz, T., Bournazou, M. N. C., Herwig, C., Kröll, P., Möller, J., Pörtner, R., & Schenkendorf, R. (2018) · Current Opinion in Chemical Engineering · doi:10.1016/j.coche.2018.11.007 · Cited by 80 · see citing works
Automated engineering of synthetic metabolic pathways for efficient biomanufacturing
Otero‐Muras, I., & Carbonell, P. (2020) · Metabolic Engineering · doi:10.1016/j.ymben.2020.11.012 · Cited by 77 · see citing works
Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime
Holmes, W. J., Darby, R. A. J., Wilks, M. D., Smith, R., & Bill, R. M. (2009) · Microbial Cell Factories · doi:10.1186/1475-2859-8-35 · Cited by 77 · see citing works
Model-Based Methods in the Biopharmaceutical Process Lifecycle
Kröll, P., Hofer, A., Ulonska, S., Kager, J., & Herwig, C. (2017) · Pharmaceutical Research · doi:10.1007/s11095-017-2308-y · Cited by 76 · see citing works
Tuber melanosporum fermentation medium optimization by Plackett–Burman design coupled with Draper–Lin small composite design and desirability function
Liu, R.-S., & Ya-jie Tang, A. (2010) · Bioresource Technology · doi:10.1016/j.biortech.2009.12.022 · Cited by 76 · see citing works
Downstream process development strategies for effective bioprocesses: Trends, progress, and combinatorial approaches
Baumann, P., & Hubbuch, J. J. (2016) · Engineering in Life Sciences · doi:10.1002/elsc.201600033 · Cited by 75 · see citing works
Comparative Assessment of the Artificial Neural Network and Response Surface Modelling Efficiencies for Biohydrogen Production on Sugar Cane Molasses
Whiteman, J. K., & Kana, E. B. G. (2013) · BioEnergy Research · doi:10.1007/s12155-013-9375-7 · Cited by 73 · see citing works
Scaling-up production of plant endophytes in bioreactors: concepts, challenges and perspectives
Ganeshan, S., Kim, S. H., & Vujanovic, V. (2021) · Bioresources and Bioprocessing · doi:10.1186/s40643-021-00417-y · Cited by 75 · see citing works
Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper–Lin small composite design
El‐Say, K. M. (2016) · Drug Design Development and Therapy · doi:10.2147/dddt.s101900 · Cited by 72 · see citing works
Protein Secretion in Gram-Positive Bacteria: From Multiple Pathways to Biotechnology
Anné, J., Economou, A., & Bernaerts, K. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_49 · Cited by 72 · see citing works
Hybrid modeling in bioprocess dynamics: Structural variabilities, implementation strategies, and practical challenges
Mahanty, B. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28503 · Cited by 72 · see citing works
An Integrated Approach to Optimizing Cellulose Mercerization
Ferro, M., Mannu, A., Panzeri, W., Theeuwen, C. H. J., & Mele, A. (2020) · Polymers · doi:10.3390/polym12071559 · Cited by 70 · see citing works
A high-throughput template for optimizingDrosophilaorgan culture with response-surface methods
Zartman, J. J., Restrepo, S., & Basler, K. (2013) · Development · doi:10.1242/dev.088872 · Cited by 68 · see citing works
Development of High-Performance Whole Cell Biosensors Aided by Statistical Modeling
Berepiki, A., Kent, R., Machado, L. F. M., & Dixon, N. (2020) · ACS Synthetic Biology · doi:10.1021/acssynbio.9b00448 · Cited by 68 · see citing works
Beyond growth rate 0.6: Corynebacterium glutamicum cultivated in highly diluted environments
Grünberger, A., van Ooyen, J., Paczia, N., Rohe, P., Schiendzielorz, G., Eggeling, L., Wiechert, W., Kohlheyer, D., & Noack, S. (2012) · Biotechnology and Bioengineering · doi:10.1002/bit.24616 · Cited by 68 · see citing works
Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites
Kim, H. U., Charusanti, P., Lee, S. Y., & Weber, T. (2016) · Natural Product Reports · doi:10.1039/c6np00019c · Cited by 67 · see citing works
Combining Genotype Improvement and Statistical Media Optimization for Isoprenoid Production in E. coli
Zhang, C., Chen, X., Zou, R., Zhou, K., Stephanopoulos, G. N., & Too, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075164 · Cited by 66 · see citing works
New Insights into Cell Culture Technology
Gowder, S. J. (2017) · InTech eBooks · doi:10.5772/62590 · Cited by 67 · see citing works
High-Throughput and Combinatorial Technologies for Tissue Engineering Applications
Peters, A., Brey, D. M., & Burdick, J. A. (2009) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2009.0049 · Cited by 63 · see citing works
Quality‐by‐Design for biotechnology‐related pharmaceuticals
Mandenius, C., Graumann, K., Schultz, T. W., Premstaller, A., Olsson, I., Petiot, E., Clemens, C., & Welin, M. (2009) · Biotechnology Journal · doi:10.1002/biot.200800333 · Cited by 63 · see citing works
Self-citation
Algorithmic co-optimization of genetic constructs and growth conditions: application to 6-ACA, a potential nylon-6 precursor
Zhou, H. L., Vonk, B., Roubos, J. A., Bovenberg, R. A. L., & Voigt, C. A. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1071 · Cited by 62 · see citing works
History and Evolution of Modeling in Biotechnology: Modeling & Simulation, Application and Hardware Performance
Noll, P., & Henkel, M. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.10.018 · Cited by 60 · see citing works
Current advances for omics-guided process optimization of microbial manufacturing
Wan, S., Liu, X., Sun, W., Lv, B., & Li, C. (2023) · Bioresources and Bioprocessing · doi:10.1186/s40643-023-00647-2 · Cited by 57 · see citing works
Comparison of bulk and microfluidics methods for the formulation of poly-lactic-co-glycolic acid (PLGA) nanoparticles modified with cell-penetrating peptides of different architectures
Streck, S., Neumann, H., Nielsen, H. M., Rades, T., & McDowell, A. (2019) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2019.100030 · Cited by 57 · see citing works
Intensified design of experiments for upstream bioreactors
von Stosch, M., & Willis, M. J. (2016) · Engineering in Life Sciences · doi:10.1002/elsc.201600037 · Cited by 56 · see citing works
Engineering Saccharomyces cerevisiae for geranylgeraniol overproduction by combinatorial design
Song, T.-Q., Ding, M., Zhai, F., Liu, D., Liu, H. S., Xiao, W., & Yuan, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-15005-4 · Cited by 56 · see citing works
Effect of carboxymethyl cellulose and baking conditions on in-vitro starch digestibility and physico-textural characteristics of low glycemic index gluten-free rice cookies
Naseer, B., Naik, H. R., Hussain, S. Z., Zargar, I. A., Beenish, Bhat, T. A., & Nazir, N. (2021) · LWT · doi:10.1016/j.lwt.2021.110885 · Cited by 56 · see citing works
Downstream processing of biopharmaceutical proteins produced in plants
Buyel, J. F., & Fischer, R. (2014) · Bioengineered · doi:10.4161/bioe.28061 · Cited by 54 · see citing works
Effective temperature shift strategy development and scale confirmation for simultaneous optimization of protein productivity and quality in Chinese hamster ovary cells
McHugh, K. P., Xu, J., Aron, K. L., Borys, M., & Li, Z. J. (2020) · Biotechnology Progress · doi:10.1002/btpr.2959 · Cited by 54 · see citing works
Medium optimization and kinetic modeling for the production of Aspergillus niger inulinase
Germeç, M., Gürler, H. N., Ozcan, A., Erkan, S. B., Karahalil, E., & Turhan, İ. (2019) · Bioprocess and Biosystems Engineering · doi:10.1007/s00449-019-02219-1 · Cited by 53 · see citing works
The use of predictive models to develop chromatography-based purification processes
Bernau, C. R., Knödler, M., Emonts, J., Jäpel, R., & Buyel, J. F. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1009102 · Cited by 53 · see citing works
Harnessing QbD, Programming Languages, and Automation for Reproducible Biology
Sadowski, M. I., Grant, C., & Fell, T. S. (2015) · Trends in biotechnology · doi:10.1016/j.tibtech.2015.11.006 · Cited by 51 · see citing works
Model‐based design of experiments for cellular processes
Chakrabarty, A., Buzzard, G. T., & Rundell, A. E. (2013) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1204 · Cited by 51 · see citing works
The Goldilocks Approach: A Review of Employing Design of Experiments in Prokaryotic Recombinant Protein Production
Uhoraningoga, A., Kinsella, G. K., HENEHAN, G. T. M., & Ryan, B. J. (2018) · Bioengineering · doi:10.3390/bioengineering5040089 · Cited by 51 · see citing works
Digital Twin Application for Model-Based DoE to Rapidly Identify Ideal Process Conditions for Space-Time Yield Optimization
Bayer, B., Diaz, R. D., Melcher, M., Striedner, G., & Duerkop, M. (2021) · Processes · doi:10.3390/pr9071109 · Cited by 47 · see citing works
Recent developments in fermentation technology: toward the next revolution in food production
Terefe, N. S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821292-9.00026-1 · Cited by 50 · see citing works
Combinatorial Analysis of Growth Factors Reveals the Contribution of Bone Morphogenetic Proteins to Chondrogenic Differentiation of Human Periosteal Cells
Mendes, L. F., Tam, W. L., Chai, Y. C., Geris, L., Luyten, F. P., & Roberts, S. J. (2016) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2015.0436 · Cited by 49 · see citing works
Autolysis of intracellular content of Brewer's spent yeast to maximize ACE-inhibitory and antioxidant activities
Vieira, E. F., Melo, A., & Ferreira, I. M. P. L. V. O. (2017) · LWT - Food Science and Technology · doi:10.1016/j.lwt.2017.04.046 · Cited by 48 · see citing works
High-throughput optimization of medium components and culture conditions for the efficient production of a lipopeptide pseudofactin by Pseudomonas fluorescens BD5
Biniarz, P., Coutte, F., Gancel, F., & Łukaszewicz, M. (2018) · Microbial Cell Factories · doi:10.1186/s12934-018-0968-x · Cited by 47 · see citing works
Design of Experiments As a Tool for Optimization in Recombinant Protein Biotechnology: From Constructs to Crystals
Papaneophytou, C. P. (2019) · Molecular Biotechnology · doi:10.1007/s12033-019-00218-x · Cited by 47 · see citing works
Design of experiment (DOE) applied to artificial neural network architecture enables rapid bioprocess improvement
Rodriguez-Granrose, D., Jones, A., Loftus, H., Tandeski, T., Heaton, W., Foley, K. T., & Silverman, L. I. (2021) · Bioprocess and Biosystems Engineering · doi:10.1007/s00449-021-02529-3 · Cited by 47 · see citing works
A systematic review on potential microbial carbohydrases: current and future perspectives
Dilshad Begum Golgeri, M., Mulla, S. I., Bagewadi, Z. K., Tyagi, S., Hu, A., Sharma, S., Bilal, M., Bharagava, R. N., Ferreira, L. F. R., Mahadevan, G. D., et al. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2106545 · Cited by 47 · see citing works
Heterotrophic and Photoautotrophic Media Optimization Using Response Surface Methodology for the Novel Microalga Chlorococcum amblystomatis
Correia, N., Pereira, H., Schulze, P. S. C., Costa, M. M., Santo, G. E., Guerra, I., Trovão, M., Barros, A. I. R. N. A., Cardoso, H., Silva, J., et al. (2023) · Applied Sciences · doi:10.3390/app13042089 · Cited by 46 · see citing works
Comparison of Modeling Methods for DoE‐Based Holistic Upstream Process Characterization
Bayer, B., von Stosch, M., Striedner, G., & Duerkop, M. (2020) · Biotechnology Journal · doi:10.1002/biot.201900551 · Cited by 46 · see citing works
Application of quality by design in optimization of nanoformulations: Principle, perspectives and practices
Birla, D., Khandale, N. B., Bashir, B., ShahbazAlam, M., Vishwas, S., Gupta, G., Dureja, H., Kumbhar, P., Disouza, J., Patravale, V. B., et al. (2024) · Drug Delivery and Translational Research · doi:10.1007/s13346-024-01681-z · Cited by 45 · see citing works
Efficacy of ascorbic acid, citric acid, ethylenediaminetetraacetic acid, and 4-hexylresorcinol as inhibitors of enzymatic browning in osmo-dehydrated fresh cut kiwis
Bhat, T. A., Rather, A. H., Hussain, S. Z., Naseer, B., Qadri, T., & Nazir, N. (2021) · Journal of Food Measurement and Characterization · doi:10.1007/s11694-021-01017-2 · Cited by 44 · see citing works
Evaluation and optimization of hepatocyte culture media factors by design of experiments (DoE) methodology
Dong, J., Mandenius, C., Lübberstedt, M., Urbaniak, T., Nussler, A. K., Knobeloch, D., Gerlach, J. C., & Zeilinger, K. (2008) · Cytotechnology · doi:10.1007/s10616-008-9168-6 · Cited by 44 · see citing works
Self-citation
Optimization of fermentation parameters in phage production using response surface methodology
Grieco, S.-H. H., Wong, A. Y. K., Dunbar, W. S., MacGillivray, R. T. A., & Curtis, S. B. (2012) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-012-1148-3 · Cited by 43 · see citing works
Comparison of mechanistic and hybrid modeling approaches for characterization of a CHO cultivation process: Requirements, pitfalls and solution paths
Bayer, B., Duerkop, M., Pörtner, R., & Möller, J. (2022) · Biotechnology Journal · doi:10.1002/biot.202200381 · Cited by 42 · see citing works
Analysis of the Effects of Five Factors Relevant to In Vitro Chondrogenesis of Human Mesenchymal Stem Cells Using Factorial Design and High Throughput mRNA-Profiling
Jakobsen, R. B., Østrup, E., Zhang, X., Mikkelsen, T. S., & Brinchmann, J. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096615 · Cited by 42 · see citing works
Enhanced growth and lipid accumulation by a new Ettlia texensis isolate under optimized photoheterotrophic condition
İşleten-Hoşoğlu, M., Ayyıldız-Tamis, D., Zengin, G., & Elibol, M. (2012) · Bioresource Technology · doi:10.1016/j.biortech.2012.12.070 · Cited by 41 · see citing works
Whole‐Cell Carboxylate Reduction for the Synthesis of 3‐Hydroxytyrosol
Napora, K., Robins, K. T., Osorio‐Lozada, A., & Winkler, M. (2014) · ChemCatChem · doi:10.1002/cctc.201300913 · Cited by 41 · see citing works
Advanced Process and Control Strategies for Bioreactors
Pörtner, R., Barradas, O. P., Frahm, B., & Hass, V. C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-444-63663-8.00016-1 · Cited by 41 · see citing works
13C Flux Analysis Reveals that Rebalancing Medium Amino Acid Composition can Reduce Ammonia Production while Preserving Central Carbon Metabolism of CHO Cell Cultures
Pereira, A. G. M., Walther, J. L., Hollenbach, M., & Young, J. D. (2018) · Biotechnology Journal · doi:10.1002/biot.201700518 · Cited by 41 · see citing works
Tunable recombinant protein expression in E. coli: enabler for continuous processing?
Marschall, L., Sagmeister, P., & Herwig, C. (2016) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-016-7550-4 · Cited by 40 · see citing works

REVIEW: BIOCATALYSTS AND BIOREACTOR DESIGN Bioprocess Optimization Using Design-of-Experiments Methodology
Mandenius, C., & Brundin, A. (2008) · Cited by 10 · see citing works
Self-citation
Design of experiments and design space approaches in the pharmaceutical bioprocess optimization
Kasemiire, A., Avohou, H. T., Bleye, C. D., Sacré, P., Dumont, E., Hubert, P., & Ziémons, E. (2021) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2021.06.004 · Cited by 85 · see citing works
POSTER PRESENTATION Open Access Model-based DoE for feed batch cultivation of a CHO cell line
Möllerl, J., Eibl, R., Eibl, D., & Pörtner, R. (2015)
Statistical Experimental Design for Bioprocess Modeling and Optimization Analysis: Repeated-Measures Method for Dynamic Biotechnology Process
Lee, K.-M., & Gilmore, D. F. (2006) · Applied Biochemistry and Biotechnology · doi:10.1385/abab:135:2:101 · Cited by 50 · see citing works
Design of Experiments (DoE) and Process Optimization. A Review of Recent Publications
Weissman, S. A., & Anderson, N. G. (2014) · Organic Process Research & Development · doi:10.1021/op500169m · Cited by 576 · see citing works

Authors: Mandenius, C., & Brundin, A.
Affiliations: Linköping University (SE)
Corresponding author: Mandenius, Carl‐Fredrik
ORCID: Mandenius, Carl‐Fredrik
Venue: Biotechnology Progress
Publisher: Wiley
Published: 2008-11
Volume: 24
Issue: 6
Pages: 1191-1203
ISSN: 1520-6033 (ISSN-L)
8756-7938
DOI: 10.1002/btpr.67
OpenAlex: W2017422800
Cited by: 422
References: 55
Citations by year: 2026: 44 · 2025: 28 · 2024: 24 · 2023: 23 · 2022: 24 · 2021: 30 · 2020: 33 · 2019: 27 · 2018: 16 · 2017: 29 · 2016: 32 · 2015: 19 · 2014: 21 · 2013: 17 · 2012: 23
FWCI: 16.36
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 23 d)
Locations: Biotechnology Progress (publishedVersion)
PubMed (publishedVersion)
Topics: Social Sciences › Decision Sciences › Management Science and Operations Research › Optimal Experimental Design Methods
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Physical Sciences › Engineering › Biomedical Engineering › Fluid Dynamics and Mixing
Keywords: bioprocess optimization, experimental design, factorial design, response surface methodology, process analytical technology, antibiotic fermentation, insect cell culture, strain screening, process development
MeSH terms: Biotechnology, Research Design

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Bioprocess optimization using design-of-experiments methodology

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks