Determination of protein concentration in downstream biomanufacturing processes by <scp>in‐line</scp> index of refraction
Steven A. Harris, Bhumit A. Patel, Adrian Gospodarek, Jayesh Desai, Alejandro de Janon, Edita Botonjic‐Sehic, Mark Brower, Nuno D. S. Pinto
Abstract
Protein concentration determination is a necessary in-process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there is a growing need to move protein concentration quantitation from off-line to in-line analysis. One solution to fulfill this process analytical technology need is an in-line index of refraction (IoR) sensor to measure protein concentration in real time. Here the performance of an IoR sensor is evaluated through a series of experiments to assess linear response, buffer matrix effects, dynamic range, sensor-to-sensor variability, and the limits of detection and quantitation. The performance of the sensor was also tested in two bioprocessing scenarios, ultrafiltration and capture chromatography. The implementation of this in-line IoR sensor for real-time protein concentration analysis and monitoring has the potential to improve continuous bioprocess manufacturing.