Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools

Detalhes bibliográficos
Autor(a) principal: Martins, Duarte Lima
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/11105
Resumo: Dissertação para obtenção do Grau de Mestre em Biotecnologia
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spelling Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design toolsVirus purificationClarificationUltrafiltrattionMembrane chromatographyBiopharmaceuticalsInnovative technologiesDissertação para obtenção do Grau de Mestre em BiotecnologiaViruses are highly efficient vectors that have been used for vaccination and gene therapy applications. However, their complexity renders downstream process particularly challenging since devices and strategies especially designed for virus purification are still lacking or need further optimization. After an introduction to the challenges of virus purification and the current strategies being employed, this dissertation presents the study of three different stages of the downstream process: clarification, ultrafiltration and chromatography. A novel clarification procedure based on diatomaceous earth was evaluated. Small-scale batch incubations led to the identification of Divergan RS – a synthetic non-charged material – as the most promising candidate for integration in a scalable filtration set-up. Ultrafiltration was addressed with the evaluation of cassette and hollow fiber modules. The results obtained show that cassette module with cut-offs in the 500 kDa range and highly hydrophilic materials enable complete recovery of infective Adenovirus while reducing process time in half when compared with the best hollow fibers. Despite the encouraging results with Adenovirus, the experiments using Retrovirus resulted in low yields and possible optimization strategies were identified. Membrane technology was also evaluated as an alternative to the packed-bed chromatography columns. By using a scale-down 96-well device, the impact of ligand density, membrane structure and feed conductivity were evaluated for the purification of Adenovirus by ion exchange chromatography. The hydrogel-grafted membrane with ligand density of 2.4 μmol cm-2 operated in bind/elute mode shown the best compromise between yield and purity. Overall, this thesis contributed to the advancement of virus purification field by exploiting innovative technologies.Fundação para a Ciência e a Tecnologia - (PTDC/EBBBIO/119501/2010)Faculdade de Ciências e TecnologiaPeixoto, CristinaMota, JoséRUNMartins, Duarte Lima2014-01-21T16:23:34Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/11105TID:201753774enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T03:45:25Zoai:run.unl.pt:10362/11105Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:20:03.386008Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
title Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
spellingShingle Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
Martins, Duarte Lima
Virus purification
Clarification
Ultrafiltrattion
Membrane chromatography
Biopharmaceuticals
Innovative technologies
title_short Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
title_full Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
title_fullStr Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
title_full_unstemmed Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
title_sort Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools
author Martins, Duarte Lima
author_facet Martins, Duarte Lima
author_role author
dc.contributor.none.fl_str_mv Peixoto, Cristina
Mota, José
RUN
dc.contributor.author.fl_str_mv Martins, Duarte Lima
dc.subject.por.fl_str_mv Virus purification
Clarification
Ultrafiltrattion
Membrane chromatography
Biopharmaceuticals
Innovative technologies
topic Virus purification
Clarification
Ultrafiltrattion
Membrane chromatography
Biopharmaceuticals
Innovative technologies
description Dissertação para obtenção do Grau de Mestre em Biotecnologia
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2014-01-21T16:23:34Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/11105
TID:201753774
url http://hdl.handle.net/10362/11105
identifier_str_mv TID:201753774
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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