Risultati finali 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. Pubblicazioni Peer reviewed articles (17) Recent capillary electrophoresis applications for upstream and downstream biopharmaceutical process monitoring Autori: van der Burg, D., Josefsson, L., Emmer, Å. and Sänger–van de Griend, C.E. Pubblicato in: TrAC Trends in Analytical Chemistry, 2023, Page(s) 116975, ISSN 0165-9936 Editore: 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. Autori: Babor, M.; Paquet-Durand, O.; Berg, C.; Büchs, J.; Hitzmann, B. Pubblicato in: Fermentation, Issue 9, 2023, Page(s) 95, ISSN 2311-5637 Editore: Basel : MDPI DOI: 10.3390/fermentation9020095 Analysis of cationic vitamins in cell culture medium samples by capillary zone electrophoresis Autori: van der Burg, D., Wätzig, H., Sänger‐van de Griend, C. E. Pubblicato in: Journal of Analytical Methods in Chemistry, Issue 2819855, 2022, ISSN 2090-8873 Editore: 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 Autori: Ihling N, Munkler LP, Paul R, Berg C, Reichenbächer B, Kadisch M, Lang D, Büchs J. Pubblicato in: Biotechnology journal, Issue 17(8), 2022, Page(s) 2100677, ISSN 1860-7314 Editore: Wiley-Blackwell DOI: 10.1002/biot.202100677 Capillary and microchip electrophoresis method development for amino acid monitoring during biopharmaceutical cultivation Autori: S. Mikkonen, L. Josefsson, M. E.-L. Mäkinen, V. Chotteau, Å. Emmer Pubblicato in: Biotechnology Journal, Issue 17, 2022, Page(s) 2100325, ISSN 1860-7314 Editore: 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. Autori: Schwarz, H., Mäkinen, M.E., Castan, A. and Chotteau, V., 2022. Pubblicato in: Biochemical Engineering Journal, Issue 182, 2022, Page(s) 108426, ISSN 1873-295X Editore: 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 Autori: Ihling N, Munkler LP, Paul R, Lang D, Büchs J Pubblicato in: Environmental Sciences Europe, Issue 34(1), 2022, Page(s) 37, ISSN 2190-4715 Editore: 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 Autori: Berg C, Ihling N, Finger M, Paquet-Durand O, Hitzmann B, Büchs J. Pubblicato in: Bioengineering, Issue 9(9), 2022, Page(s) 438, ISSN 2306-5354 Editore: Basel : MDPI DOI: 10.3390/bioengineering9090438 Practical data-driven modeling and robust predictive control of mammalian cell fed-batch process Autori: L. Dewasme, M. Mäkinen, V. Chotteau Pubblicato in: Computers and Chemical Engineering, Issue 171, 2023, Page(s) 108164, ISSN 0098-1354 Editore: 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 Autori: Saara Mikkonen, Åsa Emmer Pubblicato in: ELECTROPHORESIS, 2021, ISSN 0173-0835 Editore: John Wiley & Sons Ltd. DOI: 10.1002/elps.202100122 Generic Chemometric Models for Metabolite Concentration Prediction Based on Raman Spectra Autori: 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. Pubblicato in: Sensors, Issue 22(15), 2022, Page(s) 5581, ISSN 1424-8220 Editore: 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 Autori: Ihling N, Munkler LP, Berg C, Reichenbächer B, Wirth J, Lang D, Wagner R, Büchs J. Pubblicato in: Frontiers in Bioengineering and Biotechnology, Issue 9:725498, 2022, ISSN 2296-4185 Editore: Frontiers Media DOI: 10.3389/fbioe.2021.725498 Method development for mono‐and disaccharides monitoring in cell culture medium by capillary and microchip electrophoresis Autori: van der Burg, D., Josefsson, L., Mikkonen, S., Chotteau, V., Emmer, Å., Wätzig, H., Sänger‐van de Griend, C. E. Pubblicato in: ELECTROPHORESIS, Issue 43, 2021, Page(s) 922-929, ISSN 1522-2683 Editore: 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 Autori: Inês F Pinto, Saara Mikkonen, Leila Josefsson, Meeri E-L Mäkinen, Ruben RG Soares, Aman Russom, Åsa Emmer, Veronique Chotteau Pubblicato in: Current Opinion in Biotechnology, Issue 71, 2021, Page(s) 55-64, ISSN 0958-1669 Editore: 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. Autori: Berg, Christoph ; Herbst, Laura Marie ; Gremm, Lisa ; Ihling, Nina ; Paquet-Durand, Olivier ; Hitzmann, Bernd; Büchs, Jochen Pubblicato in: Journal of biological engineering, Issue 17, 2023, Page(s) 12, ISSN 1754-1611 Editore: 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 Autori: Inês F. Pinto, Ruben R. G. Soares, Meeri E.-L. Mäkinen, Veronique Chotteau, Aman Russom Pubblicato in: ACS Sensors, Issue 6/3, 2021, Page(s) 842-851, ISSN 2379-3694 Editore: 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. Autori: van der Burg, D., Wätzig, H., Sänger‐van de Griend, C. E. Pubblicato in: ELECTROPHORESIS, 2022, ISSN 1522-2683 Editore: 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 Autori: Berg, C., Ihling, N. and Büchs, J Pubblicato in: Chemie Ingenieur Technik, Issue 92(9), 2020, Page(s) 1206, ISSN 1522-2640 Editore: John Wiley and SOns DOI: 10.1002/cite.202055200 Book chapters (1) High-Throughput Quantification and Glycosylation Analysis of Antibodies Using Bead-Based Assays Autori: Sebastian Giehring Pubblicato in: Animal Cell Biotechnology - Methods and Protocols, Issue 2095, 2020, Page(s) 271-284, ISBN 978-1-0716-0190-7 Editore: Springer US DOI: 10.1007/978-1-0716-0191-4_15 È in corso la ricerca di dati su OpenAIRE... Si è verificato un errore durante la ricerca dei dati su OpenAIRE Nessun risultato disponibile
