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Optimal control of fed-batch fermenters S. Valentinotti† C. Cannizzaro‡ M.Rhiel‡ U. Holmberg† U. von Stockar‡ D. Bonvin† †Institut d’Automatique, EPFL, 1015 Lausanne, Switzerland ‡Institut de Genie Chimique, EPFL, 1015 Lausanne, Switzerland Fermentors are often run in a fed-batch manner to avoid the formation of overﬂow metabolites. At a high growth rate, the most eﬃcient metabolic pathway(s) of certain microorganisms become saturated resulting in overﬂow metabolite production. These byproducts are undesira

Comprehensive in-situ bioreactor monitoring and control based on a midinfrared spectroscopic sensor system M. Rhiel1, C. Cannizzaro1, S. Valentinotti2, I. Marison1, U. von Stockar1 1 Institute of Chemical Engineering, 2Institute of Automatic Control Swiss Federal Institute of Technology (EPFL), CH- 1015 Lausanne, Switzerland Abstract A mid-infrared spectroscopic sensor system consisting of a spectrometer, a single attenuated total reflectance (ATR) probe immersed in the bioreactor, and a software package fo

An in-situ, mid-IR sensor was used to monitor the major analyte concns. involved in the cultivation of Gluconacetobacter xylinus and the prodn. of gluconacetan, a food-grade exopolysaccharide. To predict the analyte concns., three different sets of std. spectra were used to develop calibration models, applying partial least-squares regression. It was possible to build a valid calibration model to predict the 700 spectra collected during the complete time course of the cultivation, using only 12 spectra coll

Mid-IR (MIR) spectroscopy in combination with partial least-squares (PLS) regression anal. was used to monitor the concns. of glucose, lactate, ammonia, and asparagine in situ during bioreactor cultivation of CHO/SSF3 cells. Simple PLS calibration models were established using referenced in situ collected single-beam spectra of one immobilized culture. The models were applied to another immobilized culture and one suspension culture. In general, glucose predictions were unbiased for both culture types. Appl

A novel approach for indirect biomass detn. in case of non-const. specific metabolic rates is reported. Specific glucose consumption rate was detd. during a first calibration culture for both free suspended and immobilized cells. It was expressed as a linear function of the limiting substrate, i. e. glucose for suspension and oxygen for immobilized cell cultures. For validation, these time-independent models were applied on a second culture presenting a different inoculum cell d. Online monitoring of the li

Since the yeast Phaffia rhodozyma was first described some 35 yr ago, there has been significant interest in the development of com. processes to exploit its ability to produce carotenoids (.apprx.80% astaxanthin). However, the optimal conditions for carotenoid prodn. are not well understood. A key limitation has been the lack of an appropriate sensor for online carotenoid quantification. In this study, an in situ Raman spectroscopy probe was used to monitor intracellular carotenoid prodn. for three consecu

A new approach for the indirect detn. of cell concn. in the case of nonconstant metabolic rates has been developed. The specific glucose-uptake rate was shown to be nonconstant in batch cultures of free suspended and immobilized CHO SSF3 cells. Time-independent models correlating the specific rate to the limiting substrate concn. were established, thus providing a continuous detn. of the specific rate through online measurement of the limiting substrate. The method could be applied to det. online cell concn

Comprehensive and cGMP suitable bioprocess monitoring is still a challenge in microbial fermn. and cell culture process development. This paper discusses the exploitation of in-situ mid-IR spectroscopy in combination with partial least-squares anal. to monitor carbohydrate, amino acid, org. acid, pH, temp., and biomass content of Saccharomyces Cerevisiae, Phaffia rhodozyma, and CHO cell cultures. Reliability of the monitored values will be discussed for potential application in cGMP environments along with

Glucose and lactate profiles in Chinese hamster ovary cell cultures were accurately monitored in real time and in situ during three bioreactor batch cultures lasting 11, 15, and 15 days performed within a 60-day period. Monitoring was accomplished using in situ-collected mid-IR spectra analyzed with a priori one-time established partial least-squares regression models. The robustness of the technique was demonstrated by application of these models without modification after 2.3 yr. Neither recalibration nor

Spectroscopic monitoring techniques have many advantages for bioprocess monitoring and control, including simultaneous multi-analyte detns., in-situ sterilizability, and low maintenance during operation. This study discusses the combined application of fluorescence, mid-IR, and Raman spectroscopic techniques for a comprehensive monitoring of Phaffia rhodozyma yeast cultures during batch and fed-batch operation for the prodn. of astaxanthin, a carotenoid of industrial importance. Reliability of the different

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Optimal Control of Fed-Batch Fermenters

Comprehensive in-situ Bioreactor Monitoring and Control Based on a Mid-Infrared Spectroscopic Sensor System

Methodology for real-time, multianalyte monitoring of fermentations using an in-situ mid-infrared sensor

Mid-infrared spectroscopic monitoring of animal cell culture bioreactor processes

Indirect biomass determination in case of non-constant metabolic rates

On-line monitoring of Phaffia rhodozyma fed-batch process with in situ dispersive raman spectroscopy

On-line determination of animal cell concentration

All-in-one bioprocess monitoring with a mid-IR spectroscopic sensor

Real-time in situ monitoring of freely suspended and immobilized cell cultures based on mid-infrared spectroscopic measurements

Bioprocess monitoring and control using the combination of fluorescence, mid-IR, and Raman spectroscopy

In-situ Monitoring and Control of Yeast Fermentations with MID-infrared Spectroscopy

Optimal Operation of Fed-Batch Fermentations via Adaptive Control of Overflow Metabolite

Fed-Batch Control of S. Cerevisiae and E. Coli at Critical Point Using Mid-FTIR Spectroscopy

In-Situ Bioreactor Monitoring and Control Based on Mid-Infrared Spectroscopic Measurements