Deliverables Documents, reports (7) Transferrable and generic chemometric model procedures are ready for application (models obtained by MBR can be used in STR) The results of the transferability of models developed using MBR to apply in STR are obtained. The conditions and procedures how to transfer are determined. Under which conditions and how models obtained by MBR can be used in STR. Off-line glycosylation/titre assays after sample purification/preparation on fluidic platform Different glycan assay formats will be tested for integration into microfluidic platform. Mechanistic models with different complexity levels related to their use (description/soft sensor/control) Mechanistic models will be derived from the experimental data and obtained through ordinary differential equation systems to describe the component concentration evolutions with respect to a kinetics and b transfersdilutions The general model complexity related to the number of considered pseudobioreactions will be based on the physical knowledge while the parameters will be identified by a dedicated identification procedure validated with the datasets Multivariable predictive robust controllers of the metabolites In accordance with available online measurements from hardware and software sensors a robust minimax nonlinear model predictive control strategy Robust NMPC will be developed to control the main metabolites ie to respect a priori optimal metabolite levels Process optimality will be described by the nonlinear constrained problem solved by the NMPController Spectrophotometric method decision-diagram for specification of best method Spectrophotometric method decisiondiagram for specification of best method Raman NIR MIR 2D fluorescence or wavelength combinations for specific applications Data-driven models with different complexity levels related to their use (description/soft sensor/control) Data-driven models will be derived by applying MLPCA to the datasets to determine the data-driven required number of pseudo-bioreactions. In a second step, a decision on the kinetic structure (grey-box vs black-box) will be taken with respect to the data content. Eventually, an adapted identification procedure will be applied and validated with the datasets. Software sensors using the previously obtained models A general observability mapping will be determined based on the previously obtained models from D8.1 and D8.2. Necessary on-line measurements will be selected and software sensors will be derived from the models and these measurements. First off-line validations of the resulting software sensors will be achieved and used as basis for further on-line validations using closed-loop controllers. Other (2) Chemometric models methodology is fixed and can be utilized by partners The best modeling methodology is determined (such as PCR, PLS or neural network, support vector regression) and can be applied by the partners Spectral pre-processing procedures (such as outlier detection, noise reduction and smoothing) are implemented The algorithms of outlier detection, noise reduction and smoothing are implemented and validated. Furthermore preprocessing procedures like deviation-, distance- and density-based approaches are implemented in the evaluation program. Publications Peer reviewed articles (17) Recent capillary electrophoresis applications for upstream and downstream biopharmaceutical process monitoring Author(s): van der Burg, D., Josefsson, L., Emmer, Å. and Sänger–van de Griend, C.E. Published in: TrAC Trends in Analytical Chemistry, 2023, Page(s) 116975, ISSN 0165-9936 Publisher: Elsevier BV DOI: 10.1016/j.trac.2023.116975 Online Process State Estimation for Hansenula polymorpha Cultivation with 2D Fluorescence Spectra-Based Chemometric Model Calibrated from a Theoretical Model in Place of Offline Measurements. Author(s): Babor, M.; Paquet-Durand, O.; Berg, C.; Büchs, J.; Hitzmann, B. Published in: Fermentation, Issue 9, 2023, Page(s) 95, ISSN 2311-5637 Publisher: Basel : MDPI DOI: 10.3390/fermentation9020095 Analysis of cationic vitamins in cell culture medium samples by capillary zone electrophoresis Author(s): van der Burg, D., Wätzig, H., Sänger‐van de Griend, C. E. Published in: Journal of Analytical Methods in Chemistry, Issue 2819855, 2022, ISSN 2090-8873 Publisher: Hindawi DOI: 10.1155/2022/2819855 Non‐invasive and time‐resolved measurement of the respiration activity of Chinese hamster ovary cells enables prediction of key culture parameters in shake flasks Author(s): Ihling N, Munkler LP, Paul R, Berg C, Reichenbächer B, Kadisch M, Lang D, Büchs J. Published in: Biotechnology journal, Issue 17(8), 2022, Page(s) 2100677, ISSN 1860-7314 Publisher: Wiley-Blackwell DOI: 10.1002/biot.202100677 Capillary and microchip electrophoresis method development for amino acid monitoring during biopharmaceutical cultivation Author(s): S. Mikkonen, L. Josefsson, M. E.-L. Mäkinen, V. Chotteau, Å. Emmer Published in: Biotechnology Journal, Issue 17, 2022, Page(s) 2100325, ISSN 1860-7314 Publisher: Wiley-Blackwell DOI: 10.1002/biot.202100325 Monitoring of amino acids and antibody N-glycosylation in high cell density perfusion culture based on Raman spectroscopy. Author(s): Schwarz, H., Mäkinen, M.E., Castan, A. and Chotteau, V., 2022. Published in: Biochemical Engineering Journal, Issue 182, 2022, Page(s) 108426, ISSN 1873-295X Publisher: Elsevier DOI: 10.1016/j.bej.2022.108426 Introducing oxygen transfer rate measurements as a novel method for time-resolved cytotoxicity assessment in shake flasks Author(s): Ihling N, Munkler LP, Paul R, Lang D, Büchs J Published in: Environmental Sciences Europe, Issue 34(1), 2022, Page(s) 37, ISSN 2190-4715 Publisher: Berlin ; Heidelberg : Springer DOI: 10.1186/s12302-022-00673-5 Online 2D Fluorescence Monitoring in Microtiter Plates Allows Prediction of Cultivation Parameters and Considerable Reduction in Sampling Efforts for Parallel Cultivations of Hansenula polymorpha Author(s): Berg C, Ihling N, Finger M, Paquet-Durand O, Hitzmann B, Büchs J. Published in: Bioengineering, Issue 9(9), 2022, Page(s) 438, ISSN 2306-5354 Publisher: Basel : MDPI DOI: 10.3390/bioengineering9090438 Practical data-driven modeling and robust predictive control of mammalian cell fed-batch process Author(s): L. Dewasme, M. Mäkinen, V. Chotteau Published in: Computers and Chemical Engineering, Issue 171, 2023, Page(s) 108164, ISSN 0098-1354 Publisher: Pergamon Press Ltd. DOI: 10.1016/j.compchemeng.2023.108164 Analysis of amino acids in cell culture supernatant using capillary electrophoresis with contactless conductivity detection Author(s): Saara Mikkonen, Åsa Emmer Published in: ELECTROPHORESIS, 2021, ISSN 0173-0835 Publisher: John Wiley & Sons Ltd. DOI: 10.1002/elps.202100122 Generic Chemometric Models for Metabolite Concentration Prediction Based on Raman Spectra Author(s): Yousefi-Darani, A., Paquet-Durand, O., Von Wrochem, A., Classen, J., Tränkle, J., Mertens, M., Snelders, J., Chotteau, V., Mäkinen, M., Handl, A., Kadisch, M., Lang, D., Dumas, P. and Hitzmann, B. Published in: Sensors, Issue 22(15), 2022, Page(s) 5581, ISSN 1424-8220 Publisher: Multidisciplinary Digital Publishing Institute (MDPI) DOI: 10.3390/s22155581 Time-Resolved Monitoring of the Oxygen Transfer Rate of Chinese Hamster Ovary Cells Provides Insights Into Culture Behavior in Shake Flasks Author(s): Ihling N, Munkler LP, Berg C, Reichenbächer B, Wirth J, Lang D, Wagner R, Büchs J. Published in: Frontiers in Bioengineering and Biotechnology, Issue 9:725498, 2022, ISSN 2296-4185 Publisher: Frontiers Media DOI: 10.3389/fbioe.2021.725498 Method development for mono‐and disaccharides monitoring in cell culture medium by capillary and microchip electrophoresis Author(s): van der Burg, D., Josefsson, L., Mikkonen, S., Chotteau, V., Emmer, Å., Wätzig, H., Sänger‐van de Griend, C. E. Published in: ELECTROPHORESIS, Issue 43, 2021, Page(s) 922-929, ISSN 1522-2683 Publisher: Wiley-VCH GmbH, Weinheim DOI: 10.1002/elps.202100213 Knowing more from less: miniaturization of ligand-binding assays and electrophoresis as new paradigms for at-line monitoring and control of mammalian cell bioprocesses Author(s): Inês F Pinto, Saara Mikkonen, Leila Josefsson, Meeri E-L Mäkinen, Ruben RG Soares, Aman Russom, Åsa Emmer, Veronique Chotteau Published in: Current Opinion in Biotechnology, Issue 71, 2021, Page(s) 55-64, ISSN 0958-1669 Publisher: Elsevier BV DOI: 10.1016/j.copbio.2021.06.018 Assessing the capabilities of 2D fluorescence monitoring in microtiter plates with data-driven modeling for secondary substrate limitation experiments of Hansenula polymorpha. Author(s): Berg, Christoph ; Herbst, Laura Marie ; Gremm, Lisa ; Ihling, Nina ; Paquet-Durand, Olivier ; Hitzmann, Bernd; Büchs, Jochen Published in: Journal of biological engineering, Issue 17, 2023, Page(s) 12, ISSN 1754-1611 Publisher: BioMed Central DOI: 10.1186/s13036-023-00332-0 Multiplexed Microfluidic Cartridge for At-Line Protein Monitoring in Mammalian Cell Culture Processes for Biopharmaceutical Production Author(s): Inês F. Pinto, Ruben R. G. Soares, Meeri E.-L. Mäkinen, Veronique Chotteau, Aman Russom Published in: ACS Sensors, Issue 6/3, 2021, Page(s) 842-851, ISSN 2379-3694 Publisher: ACS Publications DOI: 10.1021/acssensors.0c01884 Method development for quantitative monitoring of monoclonal antibodies in upstream cell culture process samples with limited sample preparation – evaluation of various capillary coatings. Author(s): van der Burg, D., Wätzig, H., Sänger‐van de Griend, C. E. Published in: ELECTROPHORESIS, 2022, ISSN 1522-2683 Publisher: Wiley-VCH GmbH, Weinheim DOI: 10.1002/elps.202200144 Conference proceedings (1) Combination of multivariate data analysis and 2D fluorescence spectroscopy in high‐throughput cultivation experiments Author(s): Berg, C., Ihling, N. and Büchs, J Published in: Chemie Ingenieur Technik, Issue 92(9), 2020, Page(s) 1206, ISSN 1522-2640 Publisher: John Wiley and SOns DOI: 10.1002/cite.202055200 Book chapters (1) High-Throughput Quantification and Glycosylation Analysis of Antibodies Using Bead-Based Assays Author(s): Sebastian Giehring Published in: Animal Cell Biotechnology - Methods and Protocols, Issue 2095, 2020, Page(s) 271-284, ISBN 978-1-0716-0190-7 Publisher: Springer US DOI: 10.1007/978-1-0716-0191-4_15 Searching for OpenAIRE data... There was an error trying to search data from OpenAIRE No results available
