Large Area Microfluidic Bioreactor for Production of Recombinant Protein

Autores
Bourguignon, Natalia; Karp, Paola Julieta; Attallah, Carolina Veronica; Chamorro, Daniel Emmanuel; Oggero Eberhardt, Marcos Rafael; Booth, Ross; Ferrero, Sol; Bhansali, Shekhar; Pérez, Maximiliano; Lerner, Betiana; Helguera, Gustavo Fernando
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To produce innovative biopharmaceuticals, highly flexible, adaptable, robust, and affordable bioprocess platforms for bioreactors are essential. In this article, we describe the development of a large-area microfluidic bioreactor (LM bioreactor) for mammalian cell culture that works at laminar flow and perfusion conditions. The 184 cm2 32 cisterns LM bioreactor is the largest polydimethylsiloxane (PDMS) microfluidic device fabricated by photopolymer flexographic master mold methodology, reaching a final volume of 2.8 mL. The LM bioreactor was connected to a syringe pump system for culture media perfusion, and the cells’ culture was monitored by photomicrograph imaging. CHO-ahIFN-α2b adherent cell line expressing the anti-hIFN- (Formula presented.) 2b recombinant scFv-Fc monoclonal antibody (mAb) for the treatment of systemic lupus erythematosus were cultured on the LM bioreactor. Cell culture and mAb production in the LM bioreactor could be sustained for 18 days. Moreover, the anti-hIFN- (Formula presented.) 2b produced in the LM bioreactor showed higher affinity and neutralizing antiproliferative activity compared to those mAbs produced in the control condition. We demonstrate for the first-time, a large area microfluidic bioreactor for mammalian cell culture that enables a controlled microenvironment suitable for the development of high-quality biologics with potential for therapeutic use.
Fil: Bourguignon, Natalia. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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: Attallah, Carolina Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Chamorro, Daniel Emmanuel. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina
Fil: Oggero Eberhardt, Marcos Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Booth, Ross. No especifíca;
Fil: Ferrero, Sol. 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: Bhansali, Shekhar. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina
Fil: Pérez, Maximiliano. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina
Fil: Lerner, Betiana. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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
Materia
ANTI-HIFN-Α2B
ANTIBODY ACTIVITY
CELL CULTURE
LARGE-AREA
MICROFLUIDIC BIOREACTOR
MONOCLONAL ANTIBODY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/213724
Acceder
id CONICETDig_e4df9dbd7d3432fe015d4eced2b38f5d
oai_identifier_str oai:ri.conicet.gov.ar:11336/213724
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Large Area Microfluidic Bioreactor for Production of Recombinant ProteinBourguignon, NataliaKarp, Paola JulietaAttallah, Carolina VeronicaChamorro, Daniel EmmanuelOggero Eberhardt, Marcos RafaelBooth, RossFerrero, SolBhansali, ShekharPérez, MaximilianoLerner, BetianaHelguera, Gustavo FernandoANTI-HIFN-Α2BANTIBODY ACTIVITYCELL CULTURELARGE-AREAMICROFLUIDIC BIOREACTORMONOCLONAL ANTIBODYhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3To produce innovative biopharmaceuticals, highly flexible, adaptable, robust, and affordable bioprocess platforms for bioreactors are essential. In this article, we describe the development of a large-area microfluidic bioreactor (LM bioreactor) for mammalian cell culture that works at laminar flow and perfusion conditions. The 184 cm2 32 cisterns LM bioreactor is the largest polydimethylsiloxane (PDMS) microfluidic device fabricated by photopolymer flexographic master mold methodology, reaching a final volume of 2.8 mL. The LM bioreactor was connected to a syringe pump system for culture media perfusion, and the cells’ culture was monitored by photomicrograph imaging. CHO-ahIFN-α2b adherent cell line expressing the anti-hIFN- (Formula presented.) 2b recombinant scFv-Fc monoclonal antibody (mAb) for the treatment of systemic lupus erythematosus were cultured on the LM bioreactor. Cell culture and mAb production in the LM bioreactor could be sustained for 18 days. Moreover, the anti-hIFN- (Formula presented.) 2b produced in the LM bioreactor showed higher affinity and neutralizing antiproliferative activity compared to those mAbs produced in the control condition. We demonstrate for the first-time, a large area microfluidic bioreactor for mammalian cell culture that enables a controlled microenvironment suitable for the development of high-quality biologics with potential for therapeutic use.Fil: Bourguignon, Natalia. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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: Attallah, Carolina Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Chamorro, Daniel Emmanuel. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; ArgentinaFil: Oggero Eberhardt, Marcos Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Booth, Ross. No especifíca;Fil: Ferrero, Sol. 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: Bhansali, Shekhar. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; ArgentinaFil: Pérez, Maximiliano. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; ArgentinaFil: Lerner, Betiana. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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; ArgentinaMDPI2022-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/213724Bourguignon, Natalia; Karp, Paola Julieta; Attallah, Carolina Veronica; Chamorro, Daniel Emmanuel; Oggero Eberhardt, Marcos Rafael; et al.; Large Area Microfluidic Bioreactor for Production of Recombinant Protein; MDPI; Biosensors; 12; 7; 7-2022; 526-5432079-6374CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/bios12070526info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:32:33Zoai:ri.conicet.gov.ar:11336/213724instacron: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 10:32:33.415CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Large Area Microfluidic Bioreactor for Production of Recombinant Protein
title Large Area Microfluidic Bioreactor for Production of Recombinant Protein
spellingShingle Large Area Microfluidic Bioreactor for Production of Recombinant Protein
Bourguignon, Natalia
ANTI-HIFN-Α2B
ANTIBODY ACTIVITY
CELL CULTURE
LARGE-AREA
MICROFLUIDIC BIOREACTOR
MONOCLONAL ANTIBODY
title_short Large Area Microfluidic Bioreactor for Production of Recombinant Protein
title_full Large Area Microfluidic Bioreactor for Production of Recombinant Protein
title_fullStr Large Area Microfluidic Bioreactor for Production of Recombinant Protein
title_full_unstemmed Large Area Microfluidic Bioreactor for Production of Recombinant Protein
title_sort Large Area Microfluidic Bioreactor for Production of Recombinant Protein
dc.creator.none.fl_str_mv Bourguignon, Natalia
Karp, Paola Julieta
Attallah, Carolina Veronica
Chamorro, Daniel Emmanuel
Oggero Eberhardt, Marcos Rafael
Booth, Ross
Ferrero, Sol
Bhansali, Shekhar
Pérez, Maximiliano
Lerner, Betiana
Helguera, Gustavo Fernando
author Bourguignon, Natalia
author_facet Bourguignon, Natalia
Karp, Paola Julieta
Attallah, Carolina Veronica
Chamorro, Daniel Emmanuel
Oggero Eberhardt, Marcos Rafael
Booth, Ross
Ferrero, Sol
Bhansali, Shekhar
Pérez, Maximiliano
Lerner, Betiana
Helguera, Gustavo Fernando
author_role author
author2 Karp, Paola Julieta
Attallah, Carolina Veronica
Chamorro, Daniel Emmanuel
Oggero Eberhardt, Marcos Rafael
Booth, Ross
Ferrero, Sol
Bhansali, Shekhar
Pérez, Maximiliano
Lerner, Betiana
Helguera, Gustavo Fernando
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTI-HIFN-Α2B
ANTIBODY ACTIVITY
CELL CULTURE
LARGE-AREA
MICROFLUIDIC BIOREACTOR
MONOCLONAL ANTIBODY
topic ANTI-HIFN-Α2B
ANTIBODY ACTIVITY
CELL CULTURE
LARGE-AREA
MICROFLUIDIC BIOREACTOR
MONOCLONAL ANTIBODY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv To produce innovative biopharmaceuticals, highly flexible, adaptable, robust, and affordable bioprocess platforms for bioreactors are essential. In this article, we describe the development of a large-area microfluidic bioreactor (LM bioreactor) for mammalian cell culture that works at laminar flow and perfusion conditions. The 184 cm2 32 cisterns LM bioreactor is the largest polydimethylsiloxane (PDMS) microfluidic device fabricated by photopolymer flexographic master mold methodology, reaching a final volume of 2.8 mL. The LM bioreactor was connected to a syringe pump system for culture media perfusion, and the cells’ culture was monitored by photomicrograph imaging. CHO-ahIFN-α2b adherent cell line expressing the anti-hIFN- (Formula presented.) 2b recombinant scFv-Fc monoclonal antibody (mAb) for the treatment of systemic lupus erythematosus were cultured on the LM bioreactor. Cell culture and mAb production in the LM bioreactor could be sustained for 18 days. Moreover, the anti-hIFN- (Formula presented.) 2b produced in the LM bioreactor showed higher affinity and neutralizing antiproliferative activity compared to those mAbs produced in the control condition. We demonstrate for the first-time, a large area microfluidic bioreactor for mammalian cell culture that enables a controlled microenvironment suitable for the development of high-quality biologics with potential for therapeutic use.
Fil: Bourguignon, Natalia. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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: Attallah, Carolina Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Chamorro, Daniel Emmanuel. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina
Fil: Oggero Eberhardt, Marcos Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Booth, Ross. No especifíca;
Fil: Ferrero, Sol. 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: Bhansali, Shekhar. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina
Fil: Pérez, Maximiliano. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina
Fil: Lerner, Betiana. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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
description To produce innovative biopharmaceuticals, highly flexible, adaptable, robust, and affordable bioprocess platforms for bioreactors are essential. In this article, we describe the development of a large-area microfluidic bioreactor (LM bioreactor) for mammalian cell culture that works at laminar flow and perfusion conditions. The 184 cm2 32 cisterns LM bioreactor is the largest polydimethylsiloxane (PDMS) microfluidic device fabricated by photopolymer flexographic master mold methodology, reaching a final volume of 2.8 mL. The LM bioreactor was connected to a syringe pump system for culture media perfusion, and the cells’ culture was monitored by photomicrograph imaging. CHO-ahIFN-α2b adherent cell line expressing the anti-hIFN- (Formula presented.) 2b recombinant scFv-Fc monoclonal antibody (mAb) for the treatment of systemic lupus erythematosus were cultured on the LM bioreactor. Cell culture and mAb production in the LM bioreactor could be sustained for 18 days. Moreover, the anti-hIFN- (Formula presented.) 2b produced in the LM bioreactor showed higher affinity and neutralizing antiproliferative activity compared to those mAbs produced in the control condition. We demonstrate for the first-time, a large area microfluidic bioreactor for mammalian cell culture that enables a controlled microenvironment suitable for the development of high-quality biologics with potential for therapeutic use.
publishDate 2022
dc.date.none.fl_str_mv 2022-07
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/11336/213724
Bourguignon, Natalia; Karp, Paola Julieta; Attallah, Carolina Veronica; Chamorro, Daniel Emmanuel; Oggero Eberhardt, Marcos Rafael; et al.; Large Area Microfluidic Bioreactor for Production of Recombinant Protein; MDPI; Biosensors; 12; 7; 7-2022; 526-543
2079-6374
CONICET Digital
CONICET
url http://hdl.handle.net/11336/213724
identifier_str_mv Bourguignon, Natalia; Karp, Paola Julieta; Attallah, Carolina Veronica; Chamorro, Daniel Emmanuel; Oggero Eberhardt, Marcos Rafael; et al.; Large Area Microfluidic Bioreactor for Production of Recombinant Protein; MDPI; Biosensors; 12; 7; 7-2022; 526-543
2079-6374
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/bios12070526
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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