At‐line monitoring of bioreactor protein production by surface plasmon resonance

Abstract

An innovative and automated method for the at-line monitoring of secreted protein was developed by harnessing a Surface Plasmon Resonance-based biosensor to a bioreactor. The proof of concept was performed by following at-line the relative concentration of a secreted protein produced by transient transfection of mammalian cells in a bioreactor. Our results suggest that our approach can be readily applied to the at-line determination of both protein concentration and bioactivity. Our experimental setup and strategy can thus satisfy the needs related to the development of novel bioprocess control protocols in the context of the new process analytical technology that arises in the biopharmaceutical industry.

Model‐based cell number quantification using online single‐oxygen sensor data for tissue engineering perfusion bioreactors

“…Depending on the bioreactor setup and cell carrier or scaffold design under consideration, this can be attributed to the high technicality and/or cost of direct, online and non-destructive measurement of TE construct CQAs. For example, imaging techniques for real-time bioprocess control in 3D TE scaffolds are limited by the resolved depth of the sample or the lack of label-free techniques (Jaccard et al, 2014;Ward et al, 2013), surface plasmon resonance or mass spectrometry techniques needs specialized setups and have issues with complex culture medium samples (Jacquemart et al, 2008;Weber et al, 2012), while biomass probes are limited to certain cell carrier materials and are unable to distinguish between viable and non-viable cells (Kiviharju et al, 2007).…”

Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications

“…While empirical models can be built to support mechanistic understanding, since they are not based on a first principles understanding, the correlations found with chemometric models are limited in their utility and in most cases cannot be extrapolated. A potential real-time on-line measurement of total concentration and a product CQA, binding rates, has been achieved by Surface Plasmon Resonance (Jacquemarte et al, 2008). This technology has not yet developed enough to be used for control in a PAT application as it is currently limited to sensing excursions from a previously modeled culture.…”

Photo‐immobilization of biological components on gold‐coated chips for measurements using surface plasmon resonance (SPR) and a quartz crystal microbalance (QCM)

“…Of the measurement methods, surface plasmon resonance (SPR) (Baac et al, 2006;Hodin et al, 2007;Jacquemart et al, 2008;Suenaga et al, 2003;Wolf et al, 2005) and quartz crystal microbalance (QCM) (Hodin et al, 2007;Jenkins et al, 2004;Nakano et al, 2007;Rawle et al, 2007;Sota et al, 2002) are very popular. For these measurements, some types of sensor chips are commercially available, although there are in general numerous immobilization methods (Rusmin et al, 2007).…”