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Título : Application of in situ near-infrared spectroscopy (NIRS) for monitoring biopharmaceuticals production by cell cultures
Autor : Zavala Ortiz, Daniel Arturo
metadata.dc.subject.other: NIRS, Cell culture
Fecha de publicación : 2020-04-29
Editorial : Tecnológico Nacional de México
metadata.dc.publisher.tecnm: Instituto Tecnológico de Veracruz
Descripción : First, a process capable of producing VC and VB was generated, cell differentiation was identified as CPP and the ability to monitor it by in situ NIR spectroscopy was firstly demonstrated using calibration models based on partial least squares regression (PLSR). Subsequently in CHO cell cultures, different regression techniques were evaluated to generate calibration models to monitor CPP and CQA. PLSR was inadequate because of the chemical and physical variability that CHO cell cultures present during the different phases of batch culture. Local Weighted Regression (LWR) was adequate to monitor classic CPP (concentration of glucose, lactate, and viable cells, amongst others) since it adequately handled the variability associated with the progression of cell culture. However, for the glycosylation profile (CQA), it was unable to properly handle the complex nonlinear relationships between NIR spectra and the concentration of various monoclonal antibody (mAb) glycoforms. This was overcome with the use of models based on support vector regressions (SVR), allowing the generation of models of different mAb glycoforms related to particular clinical effects. Globally, this work has contributed to the expansion of the capabilities of in situ NIR spectroscopy for the monitoring of classic CPP in a more precise XXIII way, new innovative CPP such as cell physiological state in plant suspension cultures, and CQA such as mAb glycosylation profiles linked to clinical characteristics in animal cell cultures
metadata.dc.type: info:eu-repo/semantics/doctoralThesis
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