Prospective inference of bioprocess cell viability through chemometric modeling of fluorescence multiway data.

Chiappini, Fabricio A; Azcarate, Silvana; Alcaraz, Mirta R; Forno, Ángela G; Goicoechea, Hector C

Chiappini, Fabricio A; Azcarate, Silvana; Alcaraz, Mirta R; Forno, Ángela G; Goicoechea, Hector C.

Afiliación

Chiappini FA; Laboratorio de Desarrollo Analítico y Quimiometría (LADAQ), Cátedra de Química Analítica I, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina.
Azcarate S; Argentinian national institution of research, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz, Argentina.
Alcaraz MR; Argentinian national institution of research, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz, Argentina.
Forno ÁG; Facultad de Ciencias Exactas y Naturales, Universidad Nacional de La Pampa, Santa Rosa, Argentina.
Goicoechea HC; Laboratorio de Desarrollo Analítico y Quimiometría (LADAQ), Cátedra de Química Analítica I, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina.

Biotechnol Prog ; 37(4): e3173, 2021 07.

Article en En | MEDLINE | ID: mdl-33969945

RESUMEN

In this investigation, the fermentation step of a standard mammalian cell-based industrial bioprocess for the production of a therapeutic protein was studied, with particular emphasis on the evolution of cell viability. This parameter constitutes one of the critical variables for bioprocess monitoring since it can affect downstream operations and the quality of the final product. In addition, when the cells experiment an unpredictable drop in viability, the assessment of this variable through classic off-line methods may not provide information sufficiently in advance to take corrective actions. In this context, Process Analytical Technology (PAT) framework aims to develop novel strategies for more efficient monitoring of critical variables, in order to improve the bioprocess performance. Thus, in this work, a set of chemometric tools were integrated to establish a PAT strategy to monitor cell viability, based on fluorescence multiway data obtained from fermentation samples of a particular bioprocess, in two different scales of operation. The spectral information, together with data regarding process variables, was integrated through chemometric exploratory tools to characterize the bioprocess and stablish novel criteria for the monitoring of cell viability. These findings motivated the development of a multivariate classification model, aiming to obtain predictive tools for the monitoring of future lots of the same bioprocess. The model could be satisfactorily fitted, showing the non-error rate of prediction of 100%.

Asunto(s)

Quimiometría; Mamíferos; Animales; Supervivencia Celular; Fermentación; Estudios Prospectivos

Palabras clave

bioprocess; cell viability monitoring; chemometrics; fluorescence second-order data; process analytical technology

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quimiometría / Mamíferos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Biotechnol Prog Asunto de la revista: BIOTECNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Argentina Pais de publicación: Estados Unidos

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