Establishment of a Perfusion Process with Antibody-Producing CHO Cells Using a 3D-Printed Microfluidic Spiral Separator with Web-Based Flow Control

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Original languageEnglish
Article number656
JournalBioengineering
Volume10
Issue number6
Early online date28 May 2023
Publication statusPublished - Jun 2023

Abstract

Monoclonal antibodies are increasingly dominating the market for human therapeutic and diagnostic agents. For this reason, continuous methods—such as perfusion processes—are being explored and optimized in an ongoing effort to increase product yields. Unfortunately, many established cell retention devices—such as tangential flow filtration—rely on membranes that are prone to clogging, fouling, and undesirable product retention at high cell densities. To circumvent these problems, in this work, we have developed a 3D-printed microfluidic spiral separator for cell retention, which can readily be adapted and replaced according to process conditions (i.e., a plug-and-play system) due to the fast and flexible 3D printing technique. In addition, this system was also expanded to include automatic flushing, web-based control, and notification via a cellphone application. This set-up constitutes a proof of concept that was successful at inducing a stable process operation at a viable cell concentration of 10–17 × 106 cells/mL in a hybrid mode (with alternating cell retention and cell bleed phases) while significantly reducing both shear stress and channel blockage. In addition to increasing efficiency to nearly 100%, this microfluidic device also improved production conditions by successfully separating dead cells and cell debris and increasing cell viability within the bioreactor.

Keywords

    3D printing, cell retention, CHO, microfluidic spiral separator, monoclonal antibodies, perfusion, web-based flow monitoring

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Cite this

Establishment of a Perfusion Process with Antibody-Producing CHO Cells Using a 3D-Printed Microfluidic Spiral Separator with Web-Based Flow Control. / Schellenberg, Jana; Dehne, Michaela; Lange, Ferdinand et al.
In: Bioengineering, Vol. 10, No. 6, 656, 06.2023.

Research output: Contribution to journalArticleResearchpeer review

Schellenberg J, Dehne M, Lange F, Scheper T, Solle D, Bahnemann J. Establishment of a Perfusion Process with Antibody-Producing CHO Cells Using a 3D-Printed Microfluidic Spiral Separator with Web-Based Flow Control. Bioengineering. 2023 Jun;10(6):656. Epub 2023 May 28. doi: 10.3390/bioengineering10060656
Schellenberg, Jana ; Dehne, Michaela ; Lange, Ferdinand et al. / Establishment of a Perfusion Process with Antibody-Producing CHO Cells Using a 3D-Printed Microfluidic Spiral Separator with Web-Based Flow Control. In: Bioengineering. 2023 ; Vol. 10, No. 6.
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abstract = "Monoclonal antibodies are increasingly dominating the market for human therapeutic and diagnostic agents. For this reason, continuous methods—such as perfusion processes—are being explored and optimized in an ongoing effort to increase product yields. Unfortunately, many established cell retention devices—such as tangential flow filtration—rely on membranes that are prone to clogging, fouling, and undesirable product retention at high cell densities. To circumvent these problems, in this work, we have developed a 3D-printed microfluidic spiral separator for cell retention, which can readily be adapted and replaced according to process conditions (i.e., a plug-and-play system) due to the fast and flexible 3D printing technique. In addition, this system was also expanded to include automatic flushing, web-based control, and notification via a cellphone application. This set-up constitutes a proof of concept that was successful at inducing a stable process operation at a viable cell concentration of 10–17 × 106 cells/mL in a hybrid mode (with alternating cell retention and cell bleed phases) while significantly reducing both shear stress and channel blockage. In addition to increasing efficiency to nearly 100%, this microfluidic device also improved production conditions by successfully separating dead cells and cell debris and increasing cell viability within the bioreactor.",
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