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Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling

Povey, Jane F., O’Malley, Christopher J., Root, Tracy, Martin, Elaine B., Montague, Gary A., Feary, Marc, Trim, Carol M., Lang, Dietmar A., Alldread, Richard, Racher, Andrew J., and others. (2014) Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling. Journal of Biotechnology, 184 . pp. 84-93. ISSN 0168-1656. (doi:10.1016/j.jbiotec.2014.04.028) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:41424)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1016/j.jbiotec.2014.04.028

Abstract

Despite many advances in the generation of high producing recombinant mammalian cell lines over the last few decades, cell line selection and development is often slowed by the inability to predict a cell line's phenotypic characteristics (e.g. growth or recombinant protein productivity) at larger scale (large volume bioreactors) using data from early cell line construction at small culture scale. Here we describe the development of an intact cell MALDI-ToF mass spectrometry fingerprinting method for mammalian cells early in the cell line construction process whereby the resulting mass spectrometry data are used to predict the phenotype of mammalian cell lines at larger culture scale using a Partial Least Squares Discriminant Analysis (PLS-DA) model. Using MALDI-ToF mass spectrometry, a library of mass spectrometry fingerprints was generated for individual cell lines at the 96 deep well plate stage of cell line development. The growth and productivity of these cell lines were evaluated in a 10 L bioreactor model of Lonza's large-scale (up to 20,000 L) fed-batch cell culture processes. Using the mass spectrometry information at the 96 deep well plate stage and phenotype information at the 10 L bioreactor scale a PLS-DA model was developed to predict the productivity of unknown cell lines at the 10 L scale based upon their MALDI-ToF fingerprint at the 96 deep well plate scale. This approach provides the basis for the very early prediction of cell lines’ performance in cGMP manufacturing-scale bioreactors and the foundation for methods and models for predicting other mammalian cell phenotypes from rapid, intact-cell mass spectrometry based measurements.

Item Type: Article
DOI/Identification number: 10.1016/j.jbiotec.2014.04.028
Uncontrolled keywords: Cell line development; Chinese hamster ovary cells; Whole cell MALDI-ToF mass spectrometry; PLS-DA modelling; Cell line prediction
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Mark Smales
Date Deposited: 13 Jun 2014 14:39 UTC
Last Modified: 29 May 2019 12:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/41424 (The current URI for this page, for reference purposes)
Smales, Christopher Mark: https://orcid.org/0000-0002-2762-4724
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