Small-scale Membrane-less Perfusion Bioreactor System for High-throughput Cell line Development and Process Optimization

The aim of this project is to develop a fully automated small-scale (<500 mL) membrane-less perfusion bioreactor system for CHO cells at very high concentration (50–100E+6 cells/mL) using a novel cell retention device based on inertial sorting.

Project status

100% Completed

Industry Need

Currently, there is no reliable scale-down model for perfusion culture to be used for cell line development and process optimization. Existing perfusion culture using hollow fiber membranes (ATF or TFF) is too difficult to maintain.

Solution

We aim to develop a fully automated smallscale (<500 mL) membrane-less perfusion bioreactor system for CHO cells at very high concentration (50–100E+6 cells/mL) using a novel cell retention device based on inertial sorting.

Outputs/Deliverables

Small-scale perfusion culture with no clogging and significantly high product recovery
Elasto-inertial microfluidics and cascaded spiral retention system for the manipulation of ultra-high-density cells (over 50 million cells/mL)
Mass-producible plastic spiral device for industrial-scale application of inertial microfluidics

Impacts

Rapid perfusion culture process development with a simple and low cost cell retention device

Fully automated small-scale perfusion culture using a membrane-less cell retention device

Publications

Jeon, H., Kwon, T., Yoon, J., & Han, J. (2022). Engineering a deformation-free plastic spiral inertial microfluidic system for CHO cell clarification in biomanufacturing. Lab on a Chip, 22(2), 272-285. https://doi.org/10.1039/d1lc00995h

Kwon, T., Choi, K., & Han, J. (2021). Separation of Ultra-High-Density Cell Suspension via Elasto-Inertial Microfluidics. Small, 17(39). https://doi.org/10.1002/smll.202101880