A multisensor approach for improved protein A load phase monitoring by conductivity-based background subtraction of UV spectra.

antibody quantification capture step partial least squares regression process analytical technology protein A chromatography

Journal

Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021

Informations de publication

Date de publication:
02 2021
Historique:
received: 24 08 2020
revised: 22 10 2020
accepted: 26 10 2020
pubmed: 6 11 2020
medline: 26 11 2021
entrez: 5 11 2020
Statut: ppublish

Résumé

Real-time monitoring and control of protein A capture steps by process analytical technologies (PATs) promises significant economic benefits due to the improved usage of the column's binding capacity, by eliminating time-consuming off-line analytics and costly resin lifetime studies, and enabling continuous production. The PAT method proposed in this study relies on ultraviolet (UV) spectroscopy with a dynamic background subtraction based on the leveling out of the conductivity signal. This point in time can be used to collect a reference spectrum for removing the majority of spectral contributions by process-related contaminants. The removal of the background spectrum facilitates chemometric model building and model accuracy. To demonstrate the benefits of this method, five different feedstocks from our industry partner were used to mix the load material for a case study. To our knowledge, such a large design space, which covers possible variations in upstream condition besides the product concentration, has not been disclosed yet. By applying the conductivity-based background subtraction, the root mean square error of prediction (RMSEP) of the partial least squares (PLS) model improved from 0.2080 to 0.0131 g

Identifiants

pubmed: 33150957
doi: 10.1002/bit.27616
doi:

Substances chimiques

Staphylococcal Protein A 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

905-917

Informations de copyright

© 2020 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals LLC.

Références

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Auteurs

Laura Rolinger (L)

Karlsruhe Institute of Technology, Karlsruhe, Germany.

Matthias Rüdt (M)

Karlsruhe Institute of Technology, Karlsruhe, Germany.

Jürgen Hubbuch (J)

Karlsruhe Institute of Technology, Karlsruhe, Germany.

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