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Visualizing medium and biodistribution in complex cell culture bioreactors using in vivo imaging
E Ratcliffe1, R J Thomas, A J Stacey
1Healthcare Engineering Research Group, Centre for Biological Engineering, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, Leicestershire, LE11 3TU, U.K.
Biotechnology Progress
|November 21, 2013
Summary
Novel 3D in vivo imaging visualizes medium flow and cell distribution in hollow fiber bioreactors. This technique aids process characterization, control, and scale-up of complex cell culture systems.
Area of Science:
- Biotechnology
- Cell Culture Engineering
- Medical Imaging
Background:
- Complex cell culture platforms, such as hollow fiber bioreactors, are crucial for stem cell-based products but lack adequate technology for process characterization and scale-up.
- Spatial heterogeneity and variability in these systems can compromise product quality and process reproducibility.
Purpose of the Study:
- To demonstrate a novel application of 3D in vivo imaging for characterizing medium flow and cell distribution within a hollow fiber bioreactor.
- To identify potential sources of variability and failure in bioreactor operation to aid process control and scale-up.
Main Methods:
- Utilized 3D in vivo imaging systems to visualize dynamic processes within a hollow fiber bioreactor.
- Employed bioluminescent murine 4T1-luc2 cells to assess cell distribution and seeding density.
- Repeatedly imaged multiple bioreactors to ensure consistency of observations.
Main Results:
- Identified medium shortcutting between inlet and outlet ports, leading to potential medium gradients.
- Observed cell localization upon inoculation, indicating variable seeding densities within the growth chamber.
- Demonstrated the capability of imaging to detect key operational bioreactor characteristics.
Conclusions:
- 3D in vivo imaging is an emerging technique for troubleshooting and optimizing bioreactor performance.
- This imaging approach can significantly aid in the process characterization, control, and scale-up of complex cell culture platforms.
- Understanding and mitigating identified sources of variation are critical for reproducible stem cell product manufacturing.
