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Artificial neural network associated to UV/Vis spectroscopy for monitoring bioreactions in biopharmaceutical processes

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Abstract

Currently, mammalian cells are the most utilized hosts for biopharmaceutical production. The culture media for these cell lines include commonly in their composition a pH indicator. Spectroscopic techniques are used for biopharmaceutical process monitoring, among them, UV–Vis spectroscopy has found scarce applications. This work aimed to define artificial neural networks architecture and fit its parameters to predict some nutrients and metabolites, as well as viable cell concentration based on UV–Vis spectral data of mammalian cell bioprocess using phenol red in culture medium. The BHK-21 cell line was used as a mammalian cell model. Off-line spectra of supernatant samples taken from batches performed at different dissolved oxygen concentrations in two bioreactor configurations and with two pH control strategies were used to define two artificial neural networks. According to absolute errors, glutamine (0.13 ± 0.14 mM), glutamate (0.02 ± 0.02 mM), glucose (1.11 ± 1.70 mM), lactate (0.84 ± 0.68 mM) and viable cell concentrations (1.89 105 ± 1.90 105 cell/mL) were suitably predicted. The prediction error averages for monitored variables were lower than those previously reported using different spectroscopic techniques in combination with partial least squares or artificial neural network. The present work allows for UV–VIS sensor development, and decreases cost related to nutrients and metabolite quantifications.

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Acknowledgments

The authors would like to thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for post-doctoral fellowship (2010/52521-6) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq: 483009/2010-5) for scientific grants.

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Authors and Affiliations

  1. Departamento de Ciências Biológicas, Universidade Estadual Paulista “Júlio de Mesquita Filho” Campus-Assis, Avenida Dom Antonio 2100, Assis, SP, 19806-900, Brazil

    Maria Beatriz Takahashi, Eutimio Gustavo Fernández Núñez & José Celso Rocha

  2. Laboratório Especial de Pesquisa e Desenvolvimento em Imunológicos Veterinários, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, SP, 05503-900, Brazil

    Jaci Leme & Celso Pereira Caricati

  3. Laboratório de Células Animais, Departamento de Engenharia Química, Escola Politécnica, Universidade de São Paulo, Av. Prof. Luciano Gualberto, trav. 3 380, São Paulo, SP, 05508-900, Brazil

    Aldo Tonso & Eutimio Gustavo Fernández Núñez

Authors
  1. Maria Beatriz Takahashi
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  2. Jaci Leme
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  3. Celso Pereira Caricati
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  4. Aldo Tonso
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  5. Eutimio Gustavo Fernández Núñez
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  6. José Celso Rocha
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Correspondence to Eutimio Gustavo Fernández Núñez.

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Takahashi, M.B., Leme, J., Caricati, C.P. et al. Artificial neural network associated to UV/Vis spectroscopy for monitoring bioreactions in biopharmaceutical processes. Bioprocess Biosyst Eng 38, 1045–1054 (2015). https://doi.org/10.1007/s00449-014-1346-7

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  • DOI: https://doi.org/10.1007/s00449-014-1346-7

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