Abstract

An extraordinary optical transmission fibre-optic surface plasmon resonance biosensing platform was engineered to improve its portability and sensitivity, and was applied to monitor the concentrations of monoclonal antibodies (Mabs). By refining the fabricating procedure and changing the material of the flow cell and the components of the optical fibre, the biosensor is portable and robust to external interference. After the implementation of an effective template cleaning procedure and precise control during the fabrication process, a consistent sensitivity of 509 ± 5 nm per refractive index unit (nm/RIU) was achieved. The biosensor can detect the Mab with a limit of detection (LOD) of 0.44 µg/mL. The results show that the biosensor is a potential tool for the rapid quantification of Mab titers. The biosensor can be regenerated at least 10 times with 10 mM glycine (pH = 2.5), and consistent signal changes were obtained after regeneration. Moreover, the employment of a spacer arm SM(PEG)2, used for immobilising protein A onto the gold film, was demonstrated to be unable to improve the detecting sensitivity; thus, a simple procedure without the spacer arm could be used to prepare the protein A-based biosensor. Our results demonstrate that the fibre-optic surface plasmon resonance biosensor is competent for the real-time and on-line monitoring of antibody titers in the future as a process analytical technologies (PATs) tool for bioprocess developments and the manufacture of therapeutic antibodies.

Highlights

  • The growth in continuous processes for therapeutic monoclonal antibodies (Mabs) production demands innovative/disruptive technologies to monitor the Mab concentration

  • One of the most remarkable features of the Extraordinary optical transmission (EOT) biosensors compared to the traditional surface plasmon resonance (SPR) biosensors is that it offers a more straightforward optical setup, facilitating miniaturisation of the sensor platform

  • Polydimethylsiloxane (PDMS) was used to fabricate a flow cell; optical fibres and microfluidic tubes were attached to the flow cell by press fits

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Summary

Introduction

The growth in continuous processes for therapeutic Mab production demands innovative/disruptive technologies to monitor the Mab concentration. The rapid at/in/on-line determination of a Mab titer is important because it provides real-time information to monitor the product yield for immediate decision-making during production [1]. It reflects the impacts of critical/key process parameters (CPPs/KPPs) on the process efficiency. Many available Mab titer measurement methods such as Patrol ultraperformance liquid chromatography and Idex Tridex protein analyser satisfy some of these crucial factors; they have distinct drawbacks such as high capital and maintenance costs, a substantially spacious dimension, poor accuracy, and low reliability [1]

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