Production of monoclonal antibodies in microfluidic devices

Autores
Bourguignon, Natalia; Attallah, Carolina Veronica; Karp, Paola Julieta; Booth, Ross; Peñaherrera Pazmiño, Ana Belén; Payés, Cristian; Oggero Eberhardt, Marcos Rafael; Perez, Maximiliano Sebastian; Helguera, Gustavo Fernando; Lerner, Betiana
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Herein, a microfluidic device with cistern design for cultivation of adherent eukaryotic cells for the production of recombinant proteins is presented. The geometric configuration of the microchannels in the device provided laminar flow with reduced velocity profiles in the cisterns, resulting in an adequate microenvironment for long-term adherent cell growth with passive pumping flow cycles of 24 hours. CHO-ahIFNα2b and HEK-ahIFNα2b adherent cell lines expressing a novel anti-hIFN-α2b recombinant monoclonal antibody (MAb) for the treatment of systemic lupus erythematosus were cultured on the surface of PDMS/glass microchannels coated with poly-d-lysine. A 24 day culture of CHO-ahIFNα2b cells resulted in MAb concentrations up to 166.4 μg mL -1 per day. The productivity of CHO-ahIFNα2b and HEK-ahIFNα2b cell lines was higher in the microdevice compared to that obtained using the adherent cell culture method (T-flask), with a 5.89- and 7.31-fold increase, respectively. Moreover, biological analysis of the MAbs produced in the microdevice showed no significant differences in the neutralizing antiproliferative activity of the hIFN-α2b or the cytokine cell signaling compared to the MAbs produced with cell adherent methods. These results suggest that this microfluidic device is suitable for long-term culture of mammalian cells and can improve the productivity of cells expressing recombinant MAbs with potential for therapeutic use without affecting the quality attributes of the product.
Fil: Bourguignon, Natalia. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Attallah, Carolina Veronica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Karp, Paola Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Booth, Ross. No especifíca;
Fil: Peñaherrera Pazmiño, Ana Belén. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Perez, Maximiliano Sebastian. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lerner, Betiana. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Materia
MICROFLUIDICS
MONOCLONAL
ANTIBODIES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/91670
Acceder
id CONICETDig_d7790c1987abdec1307df87d07b0365e
oai_identifier_str oai:ri.conicet.gov.ar:11336/91670
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Production of monoclonal antibodies in microfluidic devicesBourguignon, NataliaAttallah, Carolina VeronicaKarp, Paola JulietaBooth, RossPeñaherrera Pazmiño, Ana BelénPayés, CristianOggero Eberhardt, Marcos RafaelPerez, Maximiliano SebastianHelguera, Gustavo FernandoLerner, BetianaMICROFLUIDICSMONOCLONALANTIBODIEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Herein, a microfluidic device with cistern design for cultivation of adherent eukaryotic cells for the production of recombinant proteins is presented. The geometric configuration of the microchannels in the device provided laminar flow with reduced velocity profiles in the cisterns, resulting in an adequate microenvironment for long-term adherent cell growth with passive pumping flow cycles of 24 hours. CHO-ahIFNα2b and HEK-ahIFNα2b adherent cell lines expressing a novel anti-hIFN-α2b recombinant monoclonal antibody (MAb) for the treatment of systemic lupus erythematosus were cultured on the surface of PDMS/glass microchannels coated with poly-d-lysine. A 24 day culture of CHO-ahIFNα2b cells resulted in MAb concentrations up to 166.4 μg mL -1 per day. The productivity of CHO-ahIFNα2b and HEK-ahIFNα2b cell lines was higher in the microdevice compared to that obtained using the adherent cell culture method (T-flask), with a 5.89- and 7.31-fold increase, respectively. Moreover, biological analysis of the MAbs produced in the microdevice showed no significant differences in the neutralizing antiproliferative activity of the hIFN-α2b or the cytokine cell signaling compared to the MAbs produced with cell adherent methods. These results suggest that this microfluidic device is suitable for long-term culture of mammalian cells and can improve the productivity of cells expressing recombinant MAbs with potential for therapeutic use without affecting the quality attributes of the product.Fil: Bourguignon, Natalia. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Attallah, Carolina Veronica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Karp, Paola Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Booth, Ross. No especifíca;Fil: Peñaherrera Pazmiño, Ana Belén. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Perez, Maximiliano Sebastian. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lerner, Betiana. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaRoyal Society of Chemistry2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/91670Bourguignon, Natalia; Attallah, Carolina Veronica; Karp, Paola Julieta; Booth, Ross; Peñaherrera Pazmiño, Ana Belén; et al.; Production of monoclonal antibodies in microfluidic devices; Royal Society of Chemistry; Integrative Biology; 10; 3; 3-2018; 136-1441757-9694CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://xlink.rsc.org/?DOI=C7IB00200Ainfo:eu-repo/semantics/altIdentifier/doi/10.1039/c7ib00200ainfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:31:29Zoai:ri.conicet.gov.ar:11336/91670instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:31:29.571CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Production of monoclonal antibodies in microfluidic devices
title Production of monoclonal antibodies in microfluidic devices
spellingShingle Production of monoclonal antibodies in microfluidic devices
Bourguignon, Natalia
MICROFLUIDICS
MONOCLONAL
ANTIBODIES
title_short Production of monoclonal antibodies in microfluidic devices
title_full Production of monoclonal antibodies in microfluidic devices
title_fullStr Production of monoclonal antibodies in microfluidic devices
title_full_unstemmed Production of monoclonal antibodies in microfluidic devices
title_sort Production of monoclonal antibodies in microfluidic devices
dc.creator.none.fl_str_mv Bourguignon, Natalia
Attallah, Carolina Veronica
Karp, Paola Julieta
Booth, Ross
Peñaherrera Pazmiño, Ana Belén
Payés, Cristian
Oggero Eberhardt, Marcos Rafael
Perez, Maximiliano Sebastian
Helguera, Gustavo Fernando
Lerner, Betiana
author Bourguignon, Natalia
author_facet Bourguignon, Natalia
Attallah, Carolina Veronica
Karp, Paola Julieta
Booth, Ross
Peñaherrera Pazmiño, Ana Belén
Payés, Cristian
Oggero Eberhardt, Marcos Rafael
Perez, Maximiliano Sebastian
Helguera, Gustavo Fernando
Lerner, Betiana
author_role author
author2 Attallah, Carolina Veronica
Karp, Paola Julieta
Booth, Ross
Peñaherrera Pazmiño, Ana Belén
Payés, Cristian
Oggero Eberhardt, Marcos Rafael
Perez, Maximiliano Sebastian
Helguera, Gustavo Fernando
Lerner, Betiana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MICROFLUIDICS
MONOCLONAL
ANTIBODIES
topic MICROFLUIDICS
MONOCLONAL
ANTIBODIES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Herein, a microfluidic device with cistern design for cultivation of adherent eukaryotic cells for the production of recombinant proteins is presented. The geometric configuration of the microchannels in the device provided laminar flow with reduced velocity profiles in the cisterns, resulting in an adequate microenvironment for long-term adherent cell growth with passive pumping flow cycles of 24 hours. CHO-ahIFNα2b and HEK-ahIFNα2b adherent cell lines expressing a novel anti-hIFN-α2b recombinant monoclonal antibody (MAb) for the treatment of systemic lupus erythematosus were cultured on the surface of PDMS/glass microchannels coated with poly-d-lysine. A 24 day culture of CHO-ahIFNα2b cells resulted in MAb concentrations up to 166.4 μg mL -1 per day. The productivity of CHO-ahIFNα2b and HEK-ahIFNα2b cell lines was higher in the microdevice compared to that obtained using the adherent cell culture method (T-flask), with a 5.89- and 7.31-fold increase, respectively. Moreover, biological analysis of the MAbs produced in the microdevice showed no significant differences in the neutralizing antiproliferative activity of the hIFN-α2b or the cytokine cell signaling compared to the MAbs produced with cell adherent methods. These results suggest that this microfluidic device is suitable for long-term culture of mammalian cells and can improve the productivity of cells expressing recombinant MAbs with potential for therapeutic use without affecting the quality attributes of the product.
Fil: Bourguignon, Natalia. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Attallah, Carolina Veronica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Karp, Paola Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Booth, Ross. No especifíca;
Fil: Peñaherrera Pazmiño, Ana Belén. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Perez, Maximiliano Sebastian. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lerner, Betiana. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
description Herein, a microfluidic device with cistern design for cultivation of adherent eukaryotic cells for the production of recombinant proteins is presented. The geometric configuration of the microchannels in the device provided laminar flow with reduced velocity profiles in the cisterns, resulting in an adequate microenvironment for long-term adherent cell growth with passive pumping flow cycles of 24 hours. CHO-ahIFNα2b and HEK-ahIFNα2b adherent cell lines expressing a novel anti-hIFN-α2b recombinant monoclonal antibody (MAb) for the treatment of systemic lupus erythematosus were cultured on the surface of PDMS/glass microchannels coated with poly-d-lysine. A 24 day culture of CHO-ahIFNα2b cells resulted in MAb concentrations up to 166.4 μg mL -1 per day. The productivity of CHO-ahIFNα2b and HEK-ahIFNα2b cell lines was higher in the microdevice compared to that obtained using the adherent cell culture method (T-flask), with a 5.89- and 7.31-fold increase, respectively. Moreover, biological analysis of the MAbs produced in the microdevice showed no significant differences in the neutralizing antiproliferative activity of the hIFN-α2b or the cytokine cell signaling compared to the MAbs produced with cell adherent methods. These results suggest that this microfluidic device is suitable for long-term culture of mammalian cells and can improve the productivity of cells expressing recombinant MAbs with potential for therapeutic use without affecting the quality attributes of the product.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/91670
Bourguignon, Natalia; Attallah, Carolina Veronica; Karp, Paola Julieta; Booth, Ross; Peñaherrera Pazmiño, Ana Belén; et al.; Production of monoclonal antibodies in microfluidic devices; Royal Society of Chemistry; Integrative Biology; 10; 3; 3-2018; 136-144
1757-9694
CONICET Digital
CONICET
url http://hdl.handle.net/11336/91670
identifier_str_mv Bourguignon, Natalia; Attallah, Carolina Veronica; Karp, Paola Julieta; Booth, Ross; Peñaherrera Pazmiño, Ana Belén; et al.; Production of monoclonal antibodies in microfluidic devices; Royal Society of Chemistry; Integrative Biology; 10; 3; 3-2018; 136-144
1757-9694
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://xlink.rsc.org/?DOI=C7IB00200A
info:eu-repo/semantics/altIdentifier/doi/10.1039/c7ib00200a
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
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application/pdf
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dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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