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Determination of protein concentration in downstream biomanufacturing processes by in‐line index of refraction

Harris, Steven A., Patel, Bhumit A., Gospodarek, Adrian, Desai, Jayesh, de Janon Gutiérrez, Alejandro, Botonjic‐Sehic, Edita, Brower, Mark, Pinto, Nuno D. S.·2021·Biotechnology Progress
DOI 10.1002/btpr.3187
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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.

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  • The IoR sensor accurately measured protein concentrations during ultrafiltration and during the capture step.

    “The sensor was able to accurately measure the protein concentrations during ultrafiltration and during the capture step [109].”

    From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [109]

  • Harris et al. employed an IoR sensor in an in-line setup to measure protein concentrations in real time during the capture and ultrafiltration steps of downstream processing.

    “Harris et al. employed a sensor based on Index of Refraction (IoR) forming an in‐line setup to measure the protein concentrations in real time during the capture and ultrafiltration steps of downstream processing.”

    From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [109]

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Authors
Harris, S. A., Patel, B. A., Gospodarek, A., Desai, J., de Janon Gutiérrez, A., Botonjic‐Sehic, E., Brower, M., & Pinto, N. D. S.
Affiliations
  • Analytics Group, Digital Innovation Program Central Technology Organization, Pall Corporation Westborough Massachusetts USA
  • Analytical Research and Development Merck & Co., Inc. Kenilworth New Jersey USA
  • Biologics Process Research and Development Merck & Co., Inc. Kenilworth New Jersey USA
  • School of Chemical and Biomolecular Engineering Georgia Institute of Technology Atlanta Georgia USA
ORCID
Harris, Steven A.
Venue
Biotechnology Progress
Publisher
Wiley
Published
2021-07-06
Volume
37
Issue
5
ISSN
  • 8756-7938
  • 1520-6033
DOI
10.1002/btpr.3187
Cited by
12
References
0
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)

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