Details
| Original language | English |
|---|---|
| Article number | 656 |
| Journal | Bioengineering |
| Volume | 10 |
| Issue number | 6 |
| Early online date | 28 May 2023 |
| Publication status | Published - 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
ASJC Scopus subject areas
- Chemical Engineering(all)
- Bioengineering
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In: Bioengineering, Vol. 10, No. 6, 656, 06.2023.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Establishment of a Perfusion Process with Antibody-Producing CHO Cells Using a 3D-Printed Microfluidic Spiral Separator with Web-Based Flow Control
AU - Schellenberg, Jana
AU - Dehne, Michaela
AU - Lange, Ferdinand
AU - Scheper, Thomas
AU - Solle, Dörte
AU - Bahnemann, Janina
N1 - Funding Information: The authors would like to acknowledge and thank Sartorius Stedim Cellca GmbH, DE for providing the antibody-producing DG44 CHO cell line. Michaela Dehne is supported by the Add-on Fellowship of the Joachim Herz Foundation. Furthermore, a sincere thank you goes to Ole J. Wohlenberg and Anton Enders for their support in writing this article. Funding Information: Part of this research was funded by German Research Foundation (DFG), via the Emmy Noether Programme, grant number 346772917 (Janina Bahnemann).
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - 3D printing
KW - cell retention
KW - CHO
KW - microfluidic spiral separator
KW - monoclonal antibodies
KW - perfusion
KW - web-based flow monitoring
UR - http://www.scopus.com/inward/record.url?scp=85163742335&partnerID=8YFLogxK
U2 - 10.3390/bioengineering10060656
DO - 10.3390/bioengineering10060656
M3 - Article
AN - SCOPUS:85163742335
VL - 10
JO - Bioengineering
JF - Bioengineering
IS - 6
M1 - 656
ER -