Real‐time update of calibration model for better monitoring of batch processes using spectroscopy

Kornmann, Henri; Valentinotti, Sergio; Marison, I. W.; Stockar, Urs von

doi:10.1002/bit.20153

Cited by 13 publications

(5 citation statements)

References 39 publications

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“…These process enhancement techniques require analyzers that provide reliable real‐time information about the system. On‐line spectrometers are such devices, which, in addition, have the advantage of small sampling times, straightforward in‐situ installation, low‐maintenance requirements, inherent sterility, noninvasiveness, and nondestructiveness 3, 5–7. Near‐infrared (NIR) and Fourier transform mid‐infrared (FTIR) spectrometers, in particular, have been used successfully as on‐line analyzers of medium metabolites.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to flow circuits, mass balance equations cannot be easily established in bioprocess applications because of difficulties in identifying the presence of all relevant species and the lack of complete measurements. Nevertheless, data reconciliation has been applied successfully to obtain improved estimates of conversion rates and yield coefficients using macroscopic elemental and/or energy balances based on measurements from various process analyzers such as on‐line gas sensors, mass‐flow controllers, or reaction calorimeters 6, 16, 21–24. In the field of spectroscopy, Kornmann et al6 used data reconciliation to correct concentration estimates of medium analytes from FTIR data during batch fermentations of bacteria and used the reconciled measurements to recalibrate the instrument model on‐line.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Data reconciliation of concentration estimates from mid‐infrared and dielectric spectral measurements for improved on‐line monitoring of bioprocesses

Dabros

Amrhein

Bonvin

et al. 2009

Biotechnology Progress

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Real-time data reconciliation of concentration estimates of process analytes and biomass in microbial fermentations is investigated. A Fourier-transform mid-infrared spectrometer predicting the concentrations of process metabolites is used in parallel with a dielectric spectrometer predicting the biomass concentration during a batch fermentation of the yeast Saccharomyces cerevisiae. Calibration models developed off-line for both spectrometers suffer from poor predictive capability due to instrumental and process drifts unseen during calibration. To address this problem, the predicted metabolite and biomass concentrations, along with off-gas analysis and base addition measurements, are reconciled in real-time based on the closure of mass and elemental balances. A statistical test is used to confirm the integrity of the balances, and a non-negativity constraint is used to guide the data reconciliation algorithm toward positive concentrations. It is verified experimentally that the proposed approach reduces the standard error of prediction without the need for additional off-line analysis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Data reconciliation of concentration estimates from mid‐infrared and dielectric spectral measurements for improved on‐line monitoring of bioprocesses

Dabros

Amrhein

Bonvin

et al. 2009

Biotechnology Progress

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“…• Culture density Where low density bioreactions are concerned, MIR is the most suitable followed by Raman and then NIR. The lower detection of NIR, for example, compared with FTIR, makes the latter a desirable option for quantification at sub g/L concentrations [100] often observed in microalgal bioreactions. [21,48,102] with the exception of some analytes, for example carotenoids measured through Raman [94].…”

Section: Vibrational Spectroscopy Pat Potentialmentioning

confidence: 99%

Microalgal process-monitoring based on high-selectivity spectroscopy tools: status and future perspectives

Podevin

Fotidis

Angelidaki

2017

Critical Reviews in Biotechnology

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Microalgae are well known for their ability to accumulate lipids intracellularly, which can be used for biofuels and mitigate CO emissions. However, due to economic challenges, microalgae bioprocesses have maneuvered towards the simultaneous production of food, feed, fuel, and various high-value chemicals in a biorefinery concept. On-line and in-line monitoring of macromolecules such as lipids, proteins, carbohydrates, and high-value pigments will be more critical to maintain product quality and consistency for downstream processing in a biorefinery to maintain and valorize these markets. The main contribution of this review is to present current and prospective advances of on-line and in-line process analytical technology (PAT), with high-selectivity - the capability of monitoring several analytes simultaneously - in the interest of improving product quality, productivity, and process automation of a microalgal biorefinery. The high-selectivity PAT under consideration are mid-infrared (MIR), near-infrared (NIR), and Raman vibrational spectroscopies. The current review contains a critical assessment of these technologies in the context of recent advances in software and hardware in order to move microalgae production towards process automation through multivariate process control (MVPC) and software sensors trained on "big data". The paper will also include a comprehensive overview of off-line implementations of vibrational spectroscopy in microalgal research as it pertains to spectral interpretation and process automation to aid and motivate development.

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“…Infrared spectroscopy has the ability to monitor several of the analytes present in the culture media at any one time and as such is potentially a powerful tool in bioprocess monitoring. 5–7 Such techniques can be used in situ (in-line), making them noninvasive and eliminating the need for sample removal, thereby reducing the risk of culture contamination due to possible compromised sterility. 8 Sample preparation is not required and spectral information is obtained instantaneously.…”

Section: Introductionmentioning

confidence: 99%

Potential of Mid-Infrared Spectroscopy for On-Line Monitoring of Mammalian Cell Culture Medium Components

2012

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This study proposed a methodology to evaluate the potential of midinfrared (MIR) spectroscopy as a process analytical technology (PAT) tool for in situ (in-line) monitoring of cell culture media constituents, paving the way for on-line bioprocess monitoring and control of mammalian cell cultures. The methodology included a limit of detection (LOD) analysis and external influence investigation in addition to the calibration model development. The LOD analysis in the initial step provided a detailed procedure by which to evaluate the monitoring potential of the instrument of choice, for the application in question. The external influence study highlighted the potential difficulties when applying this technique to a typical mammalian cell culture. A comparative investigation between a fixed conduit immersion probe and flexible fiber-optic immersion probe was also carried out. Limitations associated with the use of MIR spectroscopy in the cell culture environment were also examined. A preliminary investigation, on components typically found in mammalian cell cultures, involving spectral characterization and limit of detection analysis was completed. It was evident at this initial stage that glutamine, could not be accurately detected at levels typically found in a mammalian cell culture medium. Results for glucose and ammonia, however, proved promising. A seven-concentration-level experimental design was used, and partial least squares regression employed, to develop calibration models. Optimized model results echoed the results of the preliminary analysis with the percentage error of prediction for glucose as low as 6.03% with the fixed conduit probe and glutamine having a higher error of 63.06% for the same probe. Comparison of the model results obtained from both probes supported the fixed conduit as the more accurate of the two probes for this experimental setup. The effect of external influences on the MIR spectra and hence the concentrations predicted by the model were also examined. These were subjected to statistical analysis to determine the significance of the effect. This study demonstrates that MIR spectroscopy as a PAT tool has limited potential for mammalian cell culture monitoring due to low concentrations of analytes present and outlines a method to allow the system to be evaluated.

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Real‐time update of calibration model for better monitoring of batch processes using spectroscopy

Cited by 13 publications

References 39 publications

Data reconciliation of concentration estimates from mid‐infrared and dielectric spectral measurements for improved on‐line monitoring of bioprocesses

Data reconciliation of concentration estimates from mid‐infrared and dielectric spectral measurements for improved on‐line monitoring of bioprocesses

Microalgal process-monitoring based on high-selectivity spectroscopy tools: status and future perspectives

Potential of Mid-Infrared Spectroscopy for On-Line Monitoring of Mammalian Cell Culture Medium Components

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