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Advanced near‐infrared monitor for stable real‐time measurement and control of Pichia pastoris bioprocesses
Author(s) -
Goldfeld Marina,
Christensen Jens,
Pollard David,
Gibson Elizabeth R.,
Olesberg Jonathon T.,
Koerperick Edwin J.,
Lanz Kaylee,
Small Gary W.,
Arnold Mark A.,
Evans Christine E.
Publication year - 2014
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.1890
Subject(s) - bioprocess , pichia pastoris , process analytical technology , process engineering , calibration , analyte , spectrometer , process control , environmental science , computer science , biochemical engineering , chemistry , biological system , chromatography , process (computing) , mathematics , engineering , chemical engineering , biology , biochemistry , statistics , physics , quantum mechanics , gene , recombinant dna , operating system
Near‐infrared spectroscopy is considered to be one of the most promising spectroscopic techniques for upstream bioprocess monitoring and control. Traditionally the nature of near‐infrared spectroscopy has demanded multivariate calibration models to relate spectral variance to analyte concentrations. The resulting analytical measurements have proven unreliable for the measurement of metabolic substrates for bioprocess batches performed outside the calibration process. This paper presents results of an innovative near‐infrared spectroscopic monitor designed to follow the concentrations of glycerol and methanol, as well as biomass, in real time and continuously during the production of a monoclonal antibody by a Pichia pastoris high cell density process. A solid state instrumental design overcomes the ruggedness limitations of conventional interferometer‐based spectrometers. Accurate monitoring of glycerol, methanol, and biomass is demonstrated over 274 days postcalibration. In addition, the first example of feedback control to maintain constant methanol concentrations, as low as 1 g/L, is presented. Postcalibration measurements over a 9‐month period illustrate a level of reliability and robustness that promises its adoption for online bioprocess monitoring throughout product development, from early laboratory research and development to pilot and manufacturing scale operation. © 2014 American Institute of Chemical Engineers Biotechnol. Prog ., 30:749–759, 2014