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BETA
Chotteau, Véronique, DocentORCID iD iconorcid.org/0000-0002-5370-4621
Alternative names
Publications (10 of 40) Show all publications
Wang, M., Jacobsen, E. W., Chotteau, V. & Hjalmarsson, H. (2019). A multi-step least-squares method for nonlinear rational models. In: Proceedings of the American Control Conference: . Paper presented at 2019 American Control Conference, ACC 2019; Philadelphia; United States; 10 July 2019 through 12 July 2019 (pp. 4509-4514). Institute of Electrical and Electronics Engineers (IEEE), Article ID 8814404.
Open this publication in new window or tab >>A multi-step least-squares method for nonlinear rational models
2019 (English)In: Proceedings of the American Control Conference, Institute of Electrical and Electronics Engineers (IEEE), 2019, p. 4509-4514, article id 8814404Conference paper, Published paper (Refereed)
Abstract [en]

Models rational in the parameters arise frequently in biosystems and other applications. As with all models that are non-linear in the parameters, direct parameter estimation, using e.g. nonlinear least-squares, can become challenging due to the issues of local minima and finding good initial estimates. Here we propose a multi-step least-squares method for a class of nonlinear rational models. The proposed method is applied to an extended Monod-type model. Numerical simulations indicate that the proposed method is consistent.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE), 2019
Series
Proceedings of the American Control Conference, ISSN 0743-1619
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-262599 (URN)2-s2.0-85072268828 (Scopus ID)9781538679265 (ISBN)
Conference
2019 American Control Conference, ACC 2019; Philadelphia; United States; 10 July 2019 through 12 July 2019
Note

QC 20191028

Available from: 2019-10-28 Created: 2019-10-28 Last updated: 2019-10-28Bibliographically approved
Brechmann, N. A., Eriksson, P.-O., Eriksson, K., Oscarsson, S., Buijs, J., Shokri, A., . . . Chotteau, V. (2019). Pilot-scale process for magnetic bead purification of antibodies directly from non-clarified CHO cell culture. Biotechnology progress (Print)
Open this publication in new window or tab >>Pilot-scale process for magnetic bead purification of antibodies directly from non-clarified CHO cell culture
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2019 (English)In: Biotechnology progress (Print), ISSN 8756-7938, E-ISSN 1520-6033Article in journal (Refereed) Published
Abstract [en]

High capacity magnetic protein A agarose beads, LOABeads PrtA, were used in the development

of a new process for affinity purification of monoclonal antibodies (mAbs) from non-clarified

CHO cell broth using a pilot-scale magnetic separator. The LOABeads had a maximum binding

capacity of 65 mg/mL and an adsorption capacity of 25–42 mg IgG/mL bead in suspension for an

IgG concentration of 1 to 8 g/L. Pilot-scale separation was initially tested in a mAb capture step

from 26 L clarified harvest. Small-scale experiments showed that similar mAb adsorptions were

obtained in cell broth containing 40 Å~ 106 cells/mL as in clarified supernatant. Two pilot-scale

purification runs were then performed on non-clarified cell broth from fed-batch runs of 16 L,

where a rapid mAb adsorption ≥96.6% was observed after 1 h. This process using 1 L of magnetic beads had an overall mAb yield of 86% and 16 times concentration factor. After this single protein

A capture step, the mAb purity was similar to the one obtained by column chromatography, while

the host cell protein content was very low, <10 ppm. Our results showed that this magnetic bead

mAb purification process, using a dedicated pilot-scale separation device, was a highly efficient

single step, which directly connected the culture to the downstream process without cell clarification.

Purification of mAb directly from non-clarified cell broth without cell separation can provide

significant savings in terms of resources, operation time, and equipment, compared to legacy procedure of cell separation followed by column chromatography step.

Place, publisher, year, edition, pages
AIChE, 2019
Keywords
magnetic beads, purification, monoclonal antibody, pilot-scale, downstream-bioprocess
National Category
Bioprocess Technology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-248987 (URN)10.1002/btpr.2775 (DOI)2-s2.0-85061063787 (Scopus ID)
Projects
AdBIOPRO
Funder
Vinnova, 2016-04152Vinnova, 2016-05181
Note

QC 20190429

Available from: 2019-04-11 Created: 2019-04-11 Last updated: 2019-04-29Bibliographically approved
Fons, J. G., Andersson, N., Nilsson, B., Schwarz, H. & Chotteau, V. (2019). Small scale end-to-end mAb platform with a continuous, integrated and compact process. Paper presented at National Meeting of the American-Chemical-Society (ACS), MAR 31-APR 04, 2019, Orlando, FL. Abstracts of Papers of the American Chemical Society, 257
Open this publication in new window or tab >>Small scale end-to-end mAb platform with a continuous, integrated and compact process
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2019 (English)In: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 257Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-257613 (URN)000478860501331 ()
Conference
National Meeting of the American-Chemical-Society (ACS), MAR 31-APR 04, 2019, Orlando, FL
Note

QC 20190918

Available from: 2019-09-18 Created: 2019-09-18 Last updated: 2019-09-18Bibliographically approved
Zhan, C., Hagrot, E., Brandt, L. & Chotteau, V. (2019). Study of hydrodynamics in wave bioreactors by computational fluid dynamics reveals a resonance phenomenon. Chemical Engineering Science, 193, 53-65
Open this publication in new window or tab >>Study of hydrodynamics in wave bioreactors by computational fluid dynamics reveals a resonance phenomenon
2019 (English)In: Chemical Engineering Science, ISSN 0009-2509, E-ISSN 1873-4405, Vol. 193, p. 53-65Article in journal (Refereed) Published
Abstract [en]

Culture of mammalian or human cells in Wave bioreactor is widely used for cell expansion or for biologics manufacturing. Wave bioreactor cultivation of sensitive cells such as stem cells, immune cells or anchorage-dependent cells, is recognized as an attractive option for culture in suspension or adherently on microcarriers. A systematic optimization of the mixing, oxygen transfer rate and shear stress, most favorable for the cells requires a deep understanding of the hydrodynamics inside the Wave bioreactor bag, i.e. cellbag. Numerical simulation by Computation Fluid Dynamics (CFD), is considered as an inexpensive and efficient tool for predicting the fluid behavior in many fields. In the present study, we perform numerical simulations by Ansys-FLUENT to characterize the flow conditions in a 10 L cellbag. The numerical simulations are carried out to investigate the fluid structures for nine different operating conditions of rocking speed and angle. The influence of these operating parameters on the mixing and the shear stress induced by the liquid motion are studied. We find that the mixing and shear stress increase with the cellbag angle from 4° to 7° but that increasing rocking speeds are not systematically associated with increasing mixing and shear stress. It is concluded that a resonance phenomenon is responsible for the fact that the lowest studied rocking speed, 15 rpm, generates the highest fluid velocity, mixing and shear stress compared to the higher speeds of 22 and 30 rpm.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Computation Fluid Dynamics (CFD), Hydrodynamic, Resonance, Volume of fluid (VOF), Wave bioreactor, Bioconversion, Bioreactors, Cytology, Hydrodynamics, Mammals, Mixing, Numerical models, Shear flow, Shear stress, Stem cells, Anchorage-dependent cells, Computation fluid dynamics, Different operating conditions, Operating parameters, Oxygen transfer rate, Systematic optimization, Volume of fluids, Wave bioreactors, Computational fluid dynamics
National Category
Mechanical Engineering
Identifiers
urn:nbn:se:kth:diva-236330 (URN)10.1016/j.ces.2018.08.017 (DOI)000447171800006 ()2-s2.0-85052913142 (Scopus ID)
Funder
VINNOVA, 2016-05181
Note

QC 20181120

Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2019-05-23Bibliographically approved
Hagrot, E., Oddsdóttir, H. Æ., Hosta, J. G., Jacobsen, E. W. & Chotteau, V. (2018). Retraction notice to “Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model – Application to amino acid depletion in CHO cell culture” (Journal of Biotechnology (2016) 228 (37–39)(S0168165616301213)(10.1016/j.jbiotec.2016.03.015)). Journal of Biotechnology, 265
Open this publication in new window or tab >>Retraction notice to “Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model – Application to amino acid depletion in CHO cell culture” (Journal of Biotechnology (2016) 228 (37–39)(S0168165616301213)(10.1016/j.jbiotec.2016.03.015))
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2018 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 265Article in journal (Refereed) Published
Abstract [en]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The authors of the paper wish to retract the paper due to the discovery of a calculation error in the processing of the raw data. The discovered error concerns the calculation of the specific uptake/secretion rates for several metabolites in one of the experimental conditions, i.e. glutamine omission (called Q0). In other words, in Figure 2, the variations of the metabolic fluxes for the condition Q0 are not correct. When this error is corrected, the resulting mathematical model changes (in particular for the results associated with Q0 conditions), several figures and tables are modified, and the interpretation of the fluxes in Q0 has to be slightly modified. Therefore the authors wish to retract the article. However, the error does not affect the modelling approach or the methodology presented in the article. Therefore, a revised version with the correct data has since been published: http://www.sciencedirect.com/science/article/pii/S0168165617302663. We apologize to the scientific community for the need to retract the article and the inconvenience caused.

Place, publisher, year, edition, pages
Elsevier B.V., 2018
Keywords
Erratum, retracted article
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-223179 (URN)10.1016/j.jbiotec.2017.11.013 (DOI)000418596500018 ()2-s2.0-85038872259 (Scopus ID)
Note

Export Date: 13 February 2018; Erratum; CODEN: JBITD. QC 20180228

Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-02-28Bibliographically approved
Ravichandran, R., Åstrand, C., Patra, H. K., Turner, A. P. F., Chotteau, V. & Phopase, J. (2017). Intelligent ECM mimetic injectable scaffolds based on functional collagen building blocks for tissue engineering and biomedical applications. RSC Advances, 7(34), 21068-21078
Open this publication in new window or tab >>Intelligent ECM mimetic injectable scaffolds based on functional collagen building blocks for tissue engineering and biomedical applications
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2017 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, no 34, p. 21068-21078Article in journal (Refereed) Published
Abstract [en]

Hydrogels comprising natural extracellular matrix (ECM) components are very attractive as scaffolds for regenerative medicine applications due to their inherent biointeractive properties. Responsive materials that adapt to their surrounding environments and regulate transport of ions and bioactive molecules manifest significant advantages for biomedical applications. Although there are many exciting challenges, the opportunity to design, fabricate and engineer stimuli-responsive polymeric systems based on ECM components is particularly attractive for regenerative medicine. Here we describe a one-pot approach to fabricate in situ fast gellable intelligent ECM mimetic scaffolds, based on methacrylated collagen building blocks with mechanical properties that can be modulated in the kPa-MPa range and that are suitable for both soft and hard tissues. Physiochemical characterizations demonstrate their temperature and pH responsiveness, together with the structural and enzymatic resistance that make them suitable scaffolds for long-term use in regenerative medicine and biomedical applications. The multifunctionality of these hydrogels has been demonstrated as an in situ depot-forming delivery platform for the adjustable controlled release of proteins and small drug molecules under physiological conditions and as a structural support for adhesion, proliferation and metabolic activities of human cells. The results presented herein should be useful to the design and fabrication of tailor-made scaffolds with tunable properties that retain and exhibit sustained release of growth factors for promoting tissue regeneration.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Other Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-207725 (URN)10.1039/c7ra02927f (DOI)000399722300040 ()2-s2.0-85018519019 (Scopus ID)
Note

QC 20170524

Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2017-11-29Bibliographically approved
Al-Khalili, L., Gillner, K., Zhang, Y., Åstrand, C., Shokri, A., Hughes-Brittain, N., . . . Chotteau, V. (2016). Characterization of Human CD133+Cells in Biocompatible Poly(l-lactic acid) Electrospun Nano-Fiber Scaffolds. Journal of Biomaterials and Tissue Engineering, 6(12), 959-966
Open this publication in new window or tab >>Characterization of Human CD133+Cells in Biocompatible Poly(l-lactic acid) Electrospun Nano-Fiber Scaffolds
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2016 (English)In: Journal of Biomaterials and Tissue Engineering, ISSN 2157-9083, E-ISSN 2157-9091, Vol. 6, no 12, p. 959-966Article in journal (Refereed) Published
Abstract [en]

CD133+ cells are potential myogenic progenitors for skeletal muscle regeneration to treat muscular dystrophies. The proliferation of human CD133+ stem cells was studied for 14 days in 3D biomimetic electrospun poly-L-lactic acid (PLLA) nano-fiber scaffolds. Additionally, the myogenic differentiation of the cells was studied during the last 7 days of the culture period. The cells were homogeneously distributed in the 3D scaffolds while colony formation and myotube formation occurred in 2D. After a lag phase due to lower initial cell attachment and an adaptation period, the cell growth rate in 3D was comparable to 2D after 7 and 14 days of culture. The expression of the stem cell (SC) marker PAX7 was 1.5-fold higher in 3D than 2D while the differentiation markers MyoG, Desmin and MyoD were only slightly changed (or remain unchanged) in 3D but strongly increased in 2D (12.6, 3.9, and 7.9-fold), and the myotube formation observed in 2D was absent in 3D. The marker expression during proliferation and differentiation, together with the absence of myotubes in 3D, indicates a better maintenance of stemness in 3D PLLA and stronger tendency for spontaneous differentiation in 2D culture. This makes 3D PLLA a promising biomaterial for the expansion of functional CD133+ cells.

Place, publisher, year, edition, pages
American Scientific Publishers, 2016
Keywords
Myogenic Progenitor Cell, CD133+Cells, Myogenic Differentiation, 3D Cell Culturing, Electrospun Biodegradable Nano-Fiber Scaffold
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-198952 (URN)10.1166/jbt.2016.1531 (DOI)000387148500005 ()2-s2.0-84998636398 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme
Note

QC 20170113

Available from: 2017-01-13 Created: 2016-12-22 Last updated: 2017-11-29Bibliographically approved
Hagrot, E., Oddsdóttir, H. A., Hosta, J. G., Jacobsen, E. W. & Chotteau, V. (2016). Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model - Application to amino acid depletion in CHO cell culture. Journal of Biotechnology, 228, 37-49
Open this publication in new window or tab >>Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model - Application to amino acid depletion in CHO cell culture
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2016 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 228, p. 37-49Article in journal (Refereed) Published
Abstract [en]

Mammalian cell lines are characterized by a complex and flexible metabolism. A single model that could describe the variations in metabolic behavior triggered by variations in the culture conditions would be a precious tool in bioprocess development. In this paper, we introduce an approach to generate a poly-pathway model and use it to simulate diverse metabolic states triggered in response to removal, reduction or doubling of amino acids in the culture medium of an antibody-producing CHO cell line. Macro-reactions were obtained from a metabolic network via elementary flux mode enumeration and the fluxes were modeled by kinetic equations with saturation and inhibition effects from external medium components. Importantly, one set of kinetic parameters was estimated using experimental data of the multiple metabolic states. A good fit between the model and the data was obtained for the majority of the metabolites and the experimentally observed flux variations. We find that the poly-pathway modeling approach is promising for the simulation of multiple metabolic states.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Modeling, Metabolic flux analysis, Elementary flux modes, Chinese hamster ovary cells, Amino acid metabolism, Poly-pathway model
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-189659 (URN)10.1016/j.jbiotec.2016.03.015 (DOI)000377786500008 ()27060554 (PubMedID)2-s2.0-84973333168 (Scopus ID)
Funder
VINNOVA
Note

QC 20160718

Available from: 2016-07-18 Created: 2016-07-11 Last updated: 2017-11-28Bibliographically approved
Oddsdottir, H. A., Hagrot, E., Chotteau, V. & Forsgren, A. (2016). Robustness analysis of elementary flux modes generated by column generation. Mathematical Biosciences, 273, 45-56
Open this publication in new window or tab >>Robustness analysis of elementary flux modes generated by column generation
2016 (English)In: Mathematical Biosciences, ISSN 0025-5564, E-ISSN 1879-3134, Vol. 273, p. 45-56Article in journal (Refereed) Published
Abstract [en]

Elementary flux modes (EFMs) are vectors defined from a metabolic reaction network, giving the connections between substrates and products. EFMs-based metabolic flux analysis (MFA) estimates the flux over each EFM from external flux measurements through least-squares data fitting. The measurements used in the data fitting are subject to errors. A robust optimization problem includes information on errors and gives a way to examine the sensitivity of the solution of the EFMs-based MFA to these errors. In general, formulating a robust optimization problem may make the problem significantly harder. We show that in the case of the EFMs-based MFA, when the errors are only in measurements and bounded by an interval, the robust problem can be stated as a convex quadratic programming (QP) problem. We have previously shown how the data fitting problem may be solved in a column-generation framework. In this paper, we show how column generation may be applied also to the robust problem, thereby avoiding explicit enumeration of EFMs. Furthermore, the option to indicate intervals on metabolites that are not measured is introduced in this column generation framework. The robustness of the data is evaluated in a case-study, which indicates that the solutions of our non-robust problems are in fact near-optimal also when robustness is considered, implying that the errors in measurement do not have a large impact on the optimal solution. Furthermore, we showed that the addition of intervals on unmeasured metabolites resulted in a change in the optimal solution.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Metabolic network, Robust optimization, Least-squares, Elementary flux mode, Chinese hamster ovary cell
National Category
Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:kth:diva-184008 (URN)10.1016/j.mbs.2015.12.009 (DOI)000370908500004 ()26748294 (PubMedID)2-s2.0-84960376800 (Scopus ID)
Note

QC 20160330

Available from: 2016-03-30 Created: 2016-03-22 Last updated: 2018-01-10Bibliographically approved
Zhang, Y. & Chotteau, V. (2015). Observation of Chinese Hamster Ovary Cells retained inside the non-woven fiber matrix of the CellTank bioreactor. Data in Brief, 5, 586-588
Open this publication in new window or tab >>Observation of Chinese Hamster Ovary Cells retained inside the non-woven fiber matrix of the CellTank bioreactor
2015 (English)In: Data in Brief, ISSN 2352-3409, Vol. 5, p. 586-588Article in journal (Refereed) Published
Abstract [en]

This data article shows how the recombinant Chinese Hamster Ovary (CHO) cells are located in the interstices of the matrix fibers of a CellTank bioreactor after completion of a perfusion culture, supporting the article entitled "Very high cell density perfusion of CHO cells anchored in a non-woven matrix-based bioreactor" by Zhang et al. [1]. It provides a visualization of the cell distribution in the non-woven fiber matrix in a deeper view.

Place, publisher, year, edition, pages
Elsevier, 2015
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-181839 (URN)10.1016/j.dib.2015.10.006 (DOI)2-s2.0-84945243514 (Scopus ID)
Note

QC 20160211

Available from: 2016-02-11 Created: 2016-02-05 Last updated: 2018-01-10Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5370-4621

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