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

Jana SchellenbergMichaela DehneFerdinand LangeThomas ScheperDörte SolleJanina Bahnemann
Published in: Bioengineering (Basel, Switzerland) (2023)
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 × 10 6 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.
Keyphrases
  • single cell
  • cell therapy
  • induced apoptosis
  • endothelial cells
  • stem cells
  • mental health
  • high throughput
  • machine learning
  • circulating tumor cells
  • cell death
  • deep learning