On-line near infrared bioreactor monitoring of cell density and concentrations of glucose and lactate during insect cell cultivation

Qiu, Jiang; Arnold, Mark A.; Murhammer, David W.

doi:10.1016/j.jbiotec.2014.01.009

Cited by 22 publications

(16 citation statements)

References 40 publications

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“…Life Sci. 2016, 16,[25][26][27][28][29][30][31][32][33][34][35] www.biotecvisions.com days 2 and 6, measured and predicted TCD values were similar. When cell density exceeded 20 × 10 6 cells mL −1 , the discrepancy between measured and predicted values increased exponentially.…”

Section: Online In Situ Monitoringmentioning

confidence: 99%

Process analytical technology tools for perfusion cell culture

Mercier

Rouel

Lebrun³

et al. 2015

Engineering in Life Sciences

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During cell cultivation processes for the production of biopharmaceuticals, good process performance and good product quality can be ensured by online monitoring of critical process parameters (e.g. temperature, pH, or dissolved oxygen). These data can be used in real‐time for process control, as suggested by the process analytical technology (PAT) initiative. Today, solutions for real‐time monitoring of parameters such as concentrations of cells, main nutrients, and metabolism by‐products are developing, but applications of these more complex tools in industrial settings are still limited. Here, we evaluated the use of dielectric spectroscopy (DS) and near‐infrared spectroscopy (NIRS) as PAT tools for a perfusion PER.C6® cultivation process. We showed that DS enabled predictions of viable cell density from the cultivation vessel, with a root mean square error of prediction (RMSEP) of 4.4% of the calibration range. Additionally, predictions of glucose and lactate concentrations from the cultivation vessel (RMSEP of 10 and 14%, respectively) and from the perfusion stream (RMSEP of 12 and 10%, respectively) were achieved with NIRS. We also showed that the perfusion stream offers great opportunities for noninvasive, yet frequent process monitoring. Accurate online monitoring of critical process parameters with PAT tools is the essential first step toward increased control of process output.

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Section: Online In Situ Monitoringmentioning

confidence: 99%

Process analytical technology tools for perfusion cell culture

Mercier

Rouel

Lebrun³

et al. 2015

Engineering in Life Sciences

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“…Thus, the observed mis-prediction at the beginning of the culture could be attributed to an inappropriate extrapolation. 18,22,46 Some other authors have overcome nonlinearity behavior of NIR monitoring models by using at-line analyses of clarified culture medium, as already described. The misestimations of lactate, glucose, and glutamine concentrations after 120 hr of the culture by PLSR model could also be partially explained by the nonlinearity phenomenon as formerly observed in Figure 1.…”

Section: Real Time Monitoring Of Animal Cell Culture Processesmentioning

confidence: 99%

“…44 Most of the studies, which present the use of PLSR as an efficient method to predict animal cell culture parameters using NIR spectroscopy, do not consider concentration ranges as broad as those reported here, neither the cell death-phase for the process monitoring. 18,22,46 Some other authors have overcome nonlinearity behavior of NIR monitoring models by using at-line analyses of clarified culture medium, as already described. [47][48][49] In this context, LWR has been proven as a promising method to perform in situ monitoring since it allowed calibration in a wide concentration frame, and also considered the nature of the culture medium.…”

Section: Real Time Monitoring Of Animal Cell Culture Processesmentioning

confidence: 99%

Interest of locally weighted regression to overcome nonlinear effects during in situ NIR monitoring of CHO cell culture parameters and antibody glycosylation

Zavala-Ortiz

Ebel

et al. 2019

Biotechnology Progress

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Animal cell culture processes have become the standard platform to produce therapeutic proteins such as recombinant monoclonal antibodies (mAb). Since the mAb quality could be subject to significant changes depending on manufacturing process conditions, real time monitoring and control systems are required to ensure mAb specifications mainly glycosylation and patient safety. Up to now, real time monitoring glycosylation of proteins has received scarce attention. In this article, the use of near infrared (NIR) to monitor mAb glycosylation has been reported for the first time.Whereas monitoring models are mainly constructed using linear partial least squares regressions (PLSR), evidences presented in this study indicate nonlinearity relationship between in situ captured spectra and compound concentrations, compromising the PLSR performances. A novel and simple approach was proposed to fit nonlinearity using the locally weighted regression (LWR). The LWR models were found to be more appropriate for handling information contained in spectra so that real time monitoring of cultures were accurately performed. Moreover, for the first time, the LWR calibration models allowed mAb glycosylation to be monitored, in a real time manner, by using in situ NIR spectroscopy. These results represent a further step toward developing active-control feedback of animal cell processes, particularly for ensuring properties of biologics.in situ near infrared spectroscopy, locally weighted regression-LWR, monoclonal antibody-mAb glycosylation, partial least squares regression-PLSR, real time monitoring

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“…NIRS was used by Qiu et al [32] for monitoring of glucose and lactate concentrations as well as cell density in insect cell cultivations. The cultivations were carried out in 1.6-l bioreactors.…”

Section: On-linementioning

confidence: 99%

Near-infrared spectroscopy in upstream bioprocesses

Hoehse¹,

Alves-Rausch²,

Prediger³

et al. 2015

Pharmaceutical Bioprocessing

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The quality of upstream processes and their products strongly depends on the control of all influencing parameters. However, several relevant parameters are not measured in standard bioreactor systems. Near-infrared spectroscopy (NIRS) is one promising technology capable of becoming the missing link in sensor technology. This review gives an overview of the technological principles and the technological progress. A broad range of possible applications is presented, forming in its entirety a valuable toolbox for process risk mitigation. Recent applications of NIRS in upstream bioprocesses are discussed. Moreover, the review includes regulatory aspects in implementation, calibration and validation of NIRS instrumentation and models. Key termProcess trajectory: Road of process evolution that displays whether an actual batch process runs similar to good historical batches.

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On-line near infrared bioreactor monitoring of cell density and concentrations of glucose and lactate during insect cell cultivation

Cited by 22 publications

References 40 publications

Process analytical technology tools for perfusion cell culture

Process analytical technology tools for perfusion cell culture

Interest of locally weighted regression to overcome nonlinear effects during in situ NIR monitoring of CHO cell culture parameters and antibody glycosylation

Near-infrared spectroscopy in upstream bioprocesses

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