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Cited by 5

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In-line fiber optical sensor for detection of IgG aggregates in affinity chromatography

Tran, Thuy, Gustavsson, Robert, Martinsson, Erik, Bergqvist, Filip, Axen, Andreas, Lundström, Ingemar, Mandenius, Carl-Fredrik, Aili, Daniel·2024·Journal of Chromatography A
DOI 10.1016/j.chroma.2024.465129
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Abstract

Therapeutic monoclonal antibodies (mAbs) are critical for treatment of a wide range of diseases. Immunoglobulin G (IgG) is the most predominant form of mAb but is prone to aggregation during production. Detection and removal of IgG aggregates are time-consuming and laborious. Chromatography is central for purification of biopharmaceuticals in general and essential in the production of mAbs. Protein purification systems are usually equipped with detectors for monitoring pH, UV absorbance, and conductivity, to facilitate optimization and control of the purification process. However, specific in-line detection of the target products and contaminating species, such as aggregates, is currently not possible using convectional techniques. Here we show a novel fiber optical in-line sensor, based on localized surface plasmon resonance (LSPR), for specific detection of IgG and IgG aggregates during affinity chromatography. A flow cell with a Protein A sensor chip was connected to the outlet of the affinity column connected to three different chromatography systems operating at lab scale to pilot scale. Samples containing various IgG concentrations and aggregate contents were analyzed in-line during purification on a Protein A column using both pH gradient and isocratic elution. Because of avidity effects, IgG aggregates showed slower dissociation kinetics than monomers after binding to the sensor chips. Possibilities to detect aggregate concentrations below 1 % and difference in aggreg…

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Cited by

Metadata

Authors
Tran, T., Gustavsson, R., Martinsson, E., Bergqvist, F., Axen, A., Lundström, I., Mandenius, C.-F., & Aili, D.
ORCID
Venue
Journal of Chromatography A
Publisher
Elsevier BV
Published
2024-08
Volume
1730
Pages
465129
ISSN
0021-9673
DOI
10.1016/j.chroma.2024.465129
Cited by
5
References
1
Language
en
Licence
Funders
  • Horizon 2020
  • Vinnova (2016-04120, 2019-00130)
  • Horizon 2020 Marie Skłodowska-Curie Actions (841373)

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