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Determination of protein concentration in downstream biomanufacturing processes by in-line index of refraction |
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| Authors: | Steven A Harris Bhumit A Patel Adrian Gospodarek Jayesh Desai Alejandro de Janon Gutiérrez Edita Botonjic-Sehic Mark Brower Nuno D S Pinto |
| Institution: | 1. Analytics Group, Digital Innovation Program, Central Technology Organization, Pall Corporation, Westborough, Massachusetts, USA;2. Analytical Research and Development, Merck & Co., Inc., Kenilworth, New Jersey, USA
Contribution: Conceptualization, Data curation, Formal analysis, ?Investigation, Methodology, Supervision, Writing - review & editing;3. Biologics Process Research and Development, Merck & Co., Inc., Kenilworth, New Jersey, USA Contribution: Data curation, Formal analysis;4. Analytical Research and Development, Merck & Co., Inc., Kenilworth, New Jersey, USA Contribution: Data curation, Formal analysis;5. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA Contribution: Data curation, Formal analysis;6. Analytics Group, Digital Innovation Program, Central Technology Organization, Pall Corporation, Westborough, Massachusetts, USA Contribution: Conceptualization, Data curation, Formal analysis, ?Investigation, Methodology, Supervision, Writing - review & editing;7. Biologics Process Research and Development, Merck & Co., Inc., Kenilworth, New Jersey, USA Contribution: Data curation, Formal analysis, Writing - review & editing |
| 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. |
| Keywords: | antibody bioprocessing index of refraction in-line concentration process analytical technology single-use sensor |