Optische Inline‐Messverfahren zur Zellzahl‐ und Zellgrößenbestimmung in der Bioprozesstechnik

Rudolph, G.; Brückerhoff, Thomas; Bluma, Arne; Korb, G; Scheper, Thomas

doi:10.1002/cite.200600110

Cited by 18 publications

(5 citation statements)

References 24 publications

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“…Established off-line measurement methods for cell concentration determination are for example Cedex by Roche Applied Sciences, and various systems by Beckmann Coulter [Rudolph et al, 2007]. The obvious drawback of these methods is the delay between sampling and the availability of results as well as the risk of contamination [Vojinovic et al, 2006].…”

Section: Cell and Biomass Concentrationmentioning

confidence: 99%

Process control in cell culture technology using dielectric spectroscopy

Justice¹,

Brix

Freimark³

et al. 2011

Biotechnology Advances

106

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Section: Cell and Biomass Concentrationmentioning

confidence: 99%

Process control in cell culture technology using dielectric spectroscopy

Justice¹,

Brix

Freimark³

et al. 2011

Biotechnology Advances

106

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“…Several types of in situ microscopes have been developed, varying mostly in their illumination mode and the limitation of the monitored process volume. − The results of this work are obtained using a new in situ microscope prototype which is based on the type III-XTF in situ microscope described in detail by Bluma et al in 2010 . The microscope is a transmitted-light brightfield microscope that can be integrated into 25-mm standard ports of bioreactors.…”

Section: In Situ Microscopy (Ism)mentioning

confidence: 99%

In Situ Microscopy for In-line Monitoring of the Enzymatic Hydrolysis of Cellulose

et al. 2013

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A new in-line method for the monitoring of enzymatic hydrolysis of cellulose is described. Using a new in situ microscope prototype, the noninvasive determination of particle size distributions was possible. For the automated analysis of the acquired images, a new processing algorithm called CelluloseAnalyzer was developed. It enabled tracking of the number of particles and moreover allowed monitoring of the proportions of particle size fractions during the course of enzymatic hydrolysis reactions. Using this technique, significant differences between hydrolysis with endoglucanases and cellulase mixtures were observed. Furthermore, the in situ microscopy results were compared with results from off-line measurements with laser diffraction spectroscopy and gel permeation chromatography.

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“…The viable cell concentration (VCC) is one of the most important key performance indicator (KPI) during upstream technologies in mammalian cell culture [3]. However, often the VCC is measured by an offline method that stains dead cells with Trypan Blue and a cell count is done based on microscopic image analysis [12]. Online monitoring of biomass remains challenging as new technologies are more complex to calibrate or integrate into processes [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Monitoring online biomass with a capacitance sensor during scale-up of industrially relevant CHO cell culture fed-batch processes in single-use bioreactors

Metze

Ruhl

Greller

et al. 2019

Bioprocess Biosyst Eng

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In 2004, the FDA published a guideline to implement process analytical technologies (PAT) in biopharmaceutical processes for process monitoring to gain process understanding and for the control of important process parameters. Viable cell concentration (VCC) is one of the most important key performance indicator (KPI) during mammalian cell cultivation processes. Commonly, this is measured offline. In this work, we demonstrated the comparability and scalability of linear regression models derived from online capacitance measurements. The linear regressions were used to predict the VCC and other familiar offline biomass indicators, like the viable cell volume (VCV) and the wet cell weight (WCW), in two different industrially relevant CHO cell culture processes (Process A and Process B). Therefore, different single-use bioreactor scales (50–2000 L) were used to prove feasibility and scalability of the in-line sensor integration. Coefficient of determinations of 0.79 for Process A and 0.99 for Process B for the WCW were achieved. The VCV was described with high coefficients of determination of 0.96 (Process A) and 0.98 (Process B), respectively. In agreement with other work from the literature, the VCC was only described within the exponential growth phase, but resulting in excellent coefficients of determination of 0.99 (Process A) and 0.96 (Process B), respectively. Monitoring these KPIs online using linear regression models appeared to be scale-independent, enabled deeper process understanding (e.g. here demonstrated in monitoring, the feeding profile) and showed the potential of this method for process control.

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Optische Inline‐Messverfahren zur Zellzahl‐ und Zellgrößenbestimmung in der Bioprozesstechnik

Cited by 18 publications

References 24 publications

Process control in cell culture technology using dielectric spectroscopy

Process control in cell culture technology using dielectric spectroscopy

In Situ Microscopy for In-line Monitoring of the Enzymatic Hydrolysis of Cellulose

Monitoring online biomass with a capacitance sensor during scale-up of industrially relevant CHO cell culture fed-batch processes in single-use bioreactors

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