Real-Time Chemometric Analysis of Multicomponent Bioprocesses Using Raman Spectroscopy

Author:

Weber Joerg1,Latza Andreas1,Ryabchykov Oleg1,Valet Oliver1,Storozhuk Darina2,Rathmell Cicely3,Bingemann Dieter3,Creasey David3

Affiliation:

1. Biophotonics Diagnostics GmbH

2. Leibniz Institute of Photonic Technology

3. Wasatch Photonics

Abstract

Quantitative measurement is essential for modern bioreactor synthesis, which plays a crucial role in the production of foods and pharmaceuticals. These complex processes rely on living organisms, and require fast, high-performing inline analytics for effective process control and intervention. In this study, a glycerol-fed, lab-scale E. coli bioprocess producing representative pharmaceutical compounds was monitored offline with a portable, high-sensitivity Raman spectrometer. Sampling and high performance liquid chromatography (HPLC) analysis provided the ground truth calibration for a chemometric model developed using an easy-to-use, built-for-Raman chemometric software package. The chemometric model developed demonstrates the ability of this approach to offer spectroscopic prediction of feedstock, active pharmaceutical ingredients (API), and side product concentrations. This specific combination of compact spectrometer and AI-driven analysis software opens the door for the application of real-time, continuous, and non-invasive Raman spectroscopy in bioprocess monitoring, even for users without prior chemometric or Raman experience.

Publisher

Multimedia Pharma Sciences, LLC

Reference4 articles.

1. Smith, J. E. Bioprocess/Fermentation Technology. In Biotechnology, 5th ed.; Cambridge University Press, 2009, 49–72. DOI: 10.1017/CBO9780511802751

2. Gustavsson, R.; Mandenius, C. F.; Löfgren, S.; Scheper, T.; Lindner, P. In situ Microscopy as Online Tool for Detecting Microbial Contaminations in Cell Culture, J. Biotech. 2019, 296, 53–60. DOI: 10.1016/j.jbiotec.2019.03.011

3. Challener, C. A. Advances in Inline Monitoring for Improved Bioreactor Performance: Process and bioreactor performance are directly impacted by real-time monitoring capabilities. BioPharm Int. 2023, 36 (9), 22–28. https://link.gale.com/apps/doc/A765796504/AONE?u=anon~966f443b

4. Storozhuk, D.; Ryabchykov, O.; Popp, J.; Bocklitz, T. RAMANMETRIX: A Delightful Way to Analyze Raman Spectra. arXiv preprint 2022. DOI: 10.48550/arXiv.2201.07586

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