Real-Time Nanoplasmonic Sensor for IgG Monitoring in Bioproduction

Abstract

Real-time monitoring of product titers during process development and production of biotherapeutics facilitate implementation of quality-by-design principles and enable rapid bioprocess decision and optimization of the production process. Conventional analytical methods are generally performed offline/at-line and, therefore, are not capable of generating real-time data. In this study, a novel fiber optical nanoplasmonic sensor technology was explored for rapid IgG titer measurements. The sensor combines localized surface plasmon resonance transduction and robust single use Protein A-modified sensor chips, housed in a flexible flow cell, for specific IgG detection. The sensor requires small sample volumes (1–150 µL) and shows a reproducibility and sensitivity comparable to Protein G high performance liquid chromatography-ultraviolet (HPLC-UV). The dynamic range of the sensor system can be tuned by varying the sample volume, which enables quantification of IgG samples ranging from 0.0015 to 10 mg/mL, without need for sample dilution. The sensor shows limited interference from the sample matrix and negligible unspecific protein binding. IgG titers can be rapidly determined in samples from filtered unpurified Chinese hamster ovary (CHO) cell cultures and show good correlation with enzyme-linked immunosorbent assay (ELISA).